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Wilson JB, Epstein M, Lopez B, Brown AK, Lutfy K, Friedman TC. The role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression. Front Endocrinol (Lausanne) 2023; 14:1224612. [PMID: 37664841 PMCID: PMC10470111 DOI: 10.3389/fendo.2023.1224612] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 07/25/2023] [Indexed: 09/05/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) and depression are significant public health and socioeconomic issues. They commonly co-occur, with T2DM occurring in 11.3% of the US population, while depression has a prevalence of about 9%, with higher rates among youths. Approximately 31% of patients with T2DM suffer from depressive symptoms, with 11.4% having major depressive disorders, which is twice as high as the prevalence of depression in patients without T2DM. Additionally, over 80% of people with T2DM are overweight or obese. This review describes how T2DM and depression can enhance one another, using the same molecular pathways, by synergistically altering the brain's structure and function and reducing the reward obtained from eating. In this article, we reviewed the evidence that eating, especially high-caloric foods, stimulates the limbic system, initiating Reward Deficiency Syndrome. Analogous to other addictive behaviors, neurochemical changes in those with depression and/or T2DM are thought to cause individuals to increase their food intake to obtain the same reward leading to binge eating, weight gain and obesity. Treating the symptoms of T2DM, such as lowering HbA1c, without addressing the underlying pathways has little chance of eliminating the disease. Targeting the immune system, stress circuit, melatonin, and other alterations may be more effective.
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Affiliation(s)
- Julian B. Wilson
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
| | - Ma’ayan Epstein
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
- Psychiatric Emergency Room, Olive View – University of California, Los Angeles (UCLA) Medical Center, Sylmar, CA, United States
| | - Briana Lopez
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
- Friends Research Institute, Cerritos, CA, United States
| | - Amira K. Brown
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
| | - Kabirullah Lutfy
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
| | - Theodore C. Friedman
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
- Friends Research Institute, Cerritos, CA, United States
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Grossman M, Seeley WW, Boxer AL, Hillis AE, Knopman DS, Ljubenov PA, Miller B, Piguet O, Rademakers R, Whitwell JL, Zetterberg H, van Swieten JC. Frontotemporal lobar degeneration. Nat Rev Dis Primers 2023; 9:40. [PMID: 37563165 DOI: 10.1038/s41572-023-00447-0] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2023] [Indexed: 08/12/2023]
Abstract
Frontotemporal lobar degeneration (FTLD) is one of the most common causes of early-onset dementia and presents with early social-emotional-behavioural and/or language changes that can be accompanied by a pyramidal or extrapyramidal motor disorder. About 20-25% of individuals with FTLD are estimated to carry a mutation associated with a specific FTLD pathology. The discovery of these mutations has led to important advances in potentially disease-modifying treatments that aim to slow progression or delay disease onset and has improved understanding of brain functioning. In both mutation carriers and those with sporadic disease, the most common underlying diagnoses are linked to neuronal and glial inclusions containing tau (FTLD-tau) or TDP-43 (FTLD-TDP), although 5-10% of patients may have inclusions containing proteins from the FUS-Ewing sarcoma-TAF15 family (FTLD-FET). Biomarkers definitively identifying specific pathological entities in sporadic disease have been elusive, which has impeded development of disease-modifying treatments. Nevertheless, disease-monitoring biofluid and imaging biomarkers are becoming increasingly sophisticated and are likely to serve as useful measures of treatment response during trials of disease-modifying treatments. Symptomatic trials using novel approaches such as transcranial direct current stimulation are also beginning to show promise.
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Affiliation(s)
- Murray Grossman
- Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, USA
| | - William W Seeley
- Departments of Neurology and Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
- Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
| | - Adam L Boxer
- Departments of Neurology and Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA
| | - Argye E Hillis
- Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
| | | | - Peter A Ljubenov
- Departments of Neurology and Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA
| | - Bruce Miller
- Departments of Neurology and Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA
| | - Olivier Piguet
- School of Psychology and Brain and Mind Center, University of Sydney, Sydney, New South Wales, Australia
| | - Rosa Rademakers
- VIB Center for Molecular Neurology, University of Antwerp, Antwerp, Belgium
| | | | - Henrik Zetterberg
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The University of Gothenburg, Mölndal, Sweden
- Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
- Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
- UK Dementia Research Institute at UCL, London, UK
- Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
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Kang JS, Baek JH, Song MY, Rehman NU, Chung HJ, Lee DK, Yoo DY, Kim HJ. Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 324:121387. [PMID: 36870594 DOI: 10.1016/j.envpol.2023.121387] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/21/2023] [Accepted: 03/01/2023] [Indexed: 06/18/2023]
Abstract
Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected. But, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. In this study, we assessed the consequences of daily DEHP ingestion (2 and 20 mg/kg diets) in male mice for at least 100 days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. We found the marked depressive behaviors and reduced learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress were increased in plasma and brain tissues. Long-term DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The reduced glutamatergic neurotransmission activity caused by DEHP ingestion was demonstrated using an electrophysiological method. This study revealed that long-term exposure to DEHP is hazardous and can cause neurobehavioral disorders, even at daily exposure levels.
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Affiliation(s)
- Jae Soon Kang
- Department of Anatomy and Convergence Medical Sciences, Institute of Health Sciences, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University Medical School, 15 Jinju-daero 816 Beongil, Jinju, Gyeongnam, 52727, Republic of Korea
| | - Ji Hyeong Baek
- Department of Anatomy and Convergence Medical Sciences, Institute of Health Sciences, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University Medical School, 15 Jinju-daero 816 Beongil, Jinju, Gyeongnam, 52727, Republic of Korea
| | - Mi Yeong Song
- Department of Anatomy and Convergence Medical Sciences, Institute of Health Sciences, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University Medical School, 15 Jinju-daero 816 Beongil, Jinju, Gyeongnam, 52727, Republic of Korea
| | - Naveed Ur Rehman
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam, 52828, Republic of Korea
| | - Hye Jin Chung
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam, 52828, Republic of Korea
| | - Dong Kun Lee
- Department of Physiology, Institute of Health Sciences, Tyrosine Peptide Multiuse Research Group, Gyeongsang National University Medical School, 15 Jinju-daero 816 Beongil, Jinju, Gyeongnam, 52727, Republic of Korea
| | - Dae Young Yoo
- Department of Anatomy and Convergence Medical Sciences, Institute of Health Sciences, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University Medical School, 15 Jinju-daero 816 Beongil, Jinju, Gyeongnam, 52727, Republic of Korea
| | - Hyun Joon Kim
- Department of Anatomy and Convergence Medical Sciences, Institute of Health Sciences, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University Medical School, 15 Jinju-daero 816 Beongil, Jinju, Gyeongnam, 52727, Republic of Korea.
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Alosco ML, Barr WB, Banks SJ, Wethe JV, Miller JB, Pulukuri SV, Culhane J, Tripodis Y, Adler CH, Balcer LJ, Bernick C, Mariani ML, Cantu RC, Dodick DW, McClean MD, Au R, Mez J, Turner RW, Palmisano JN, Martin B, Hartlage K, Cummings JL, Reiman EM, Shenton ME, Stern RA, Chen K, Protas H, Boker C, Farrer L, Helm R, Katz DI, Kowall N, Mercier G, Otis J, Weller J, Simkin I, Andino A, Conneely S, Diamond C, Fagle T, Haller O, Hunt T, Gullotti N, Mayville B, McLaughlin K, Nanna M, Platt T, Rice F, Sestak M, Annis D, Chaisson C, Dixon DB, Finney C, Gallagher K, Lu J, Ojo E, Pine B, Ramachandran J, Bouix S, Fitzsimmons J, Lin AP, Koerte IK, Pasternak O, Arciniega H, Billah T, Bonke E, Breedlove K, Coello E, Coleman MJ, Jung L, Liao H, Loy M, Rizzoni E, Schultz V, Silva A, Vessey B, Wiegand TLT, Ritter A, Sabbagh M, de la Cruz R, Durant J, Golceker M, Harmon N, Kaylegian K, Long R, Nance C, Sandoval P, Marek KL, Serrano A, Geda Y, Falk B, Duffy A, Howard M, Montague M, Osgood T, Babcock D, Bellgowan P, Goldberg J, Wisniewski T, Kirov I, Lui Y, Marmar C, Hasanaj L, Serrano L, Al-Kharafi A, George A, Martin S, Riley E, Runge W, Peskind ER, Colasurdo E, Marcus DS, Gurney J, Greenwald R, Johnson KA. Neuropsychological test performance of former American football players. Alzheimers Res Ther 2023; 15:1. [PMID: 36597138 PMCID: PMC9808953 DOI: 10.1186/s13195-022-01147-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. METHODS One hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. RESULTS Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. CONCLUSIONS In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.
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Affiliation(s)
- Michael L. Alosco
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA
| | - William B. Barr
- grid.137628.90000 0004 1936 8753Department of Neurology, NYU Grossman School of Medicine, New York, NY USA
| | - Sarah J. Banks
- grid.266100.30000 0001 2107 4242Department of Neuroscience, University of California, San Diego, CA USA ,grid.266100.30000 0001 2107 4242Department of Psychiatry, University of California, San Diego, CA USA
| | - Jennifer V. Wethe
- grid.417468.80000 0000 8875 6339Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ USA
| | - Justin B. Miller
- grid.239578.20000 0001 0675 4725Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV USA
| | - Surya Vamsi Pulukuri
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA
| | - Julia Culhane
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA
| | - Yorghos Tripodis
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA ,grid.189504.10000 0004 1936 7558Department of Biostatistics, Boston University School of Public Health, Boston, MA USA
| | - Charles H. Adler
- grid.417468.80000 0000 8875 6339Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ USA
| | - Laura J. Balcer
- grid.137628.90000 0004 1936 8753Department of Neurology, NYU Grossman School of Medicine, New York, NY USA ,grid.137628.90000 0004 1936 8753Department of Population Health, NYU Grossman School of Medicine, New York, NY USA ,grid.137628.90000 0004 1936 8753Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY USA
| | - Charles Bernick
- grid.239578.20000 0001 0675 4725Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV USA ,grid.34477.330000000122986657Department of Neurology, University of Washington, Seattle, WA USA
| | - Megan L. Mariani
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA
| | - Robert C. Cantu
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA
| | - David W. Dodick
- grid.417468.80000 0000 8875 6339Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ USA
| | - Michael D. McClean
- grid.189504.10000 0004 1936 7558Department of Environmental Health, Boston University School of Public Health, Boston, MA USA
| | - Rhoda Au
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA ,grid.510954.c0000 0004 0444 3861Framingham Heart Study, Framingham, MA USA ,grid.189504.10000 0004 1936 7558Slone Epidemiology Center, Boston University, Boston, MA USA ,grid.189504.10000 0004 1936 7558Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA ,grid.189504.10000 0004 1936 7558Department of Epidemiology, Boston University School of Public Health, Boston, MA USA
| | - Jesse Mez
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA ,grid.510954.c0000 0004 0444 3861Framingham Heart Study, Framingham, MA USA
| | - Robert W. Turner
- grid.253615.60000 0004 1936 9510Department of Clinical Research & Leadership, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA
| | - Joseph N. Palmisano
- grid.189504.10000 0004 1936 7558Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA USA
| | - Brett Martin
- grid.189504.10000 0004 1936 7558Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA USA
| | - Kaitlin Hartlage
- grid.189504.10000 0004 1936 7558Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA USA
| | - Jeffrey L. Cummings
- grid.272362.00000 0001 0806 6926Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV USA
| | - Eric M. Reiman
- Banner Alzheimer’s Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer’s Consortium, Phoenix, AZ USA
| | - Martha E. Shenton
- grid.62560.370000 0004 0378 8294Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Department of Radiology, Brigham and Women’s Hospital, Boston, MA USA ,grid.410370.10000 0004 4657 1992VA Boston Healthcare System, Boston, MA USA
| | - Robert A. Stern
- grid.189504.10000 0004 1936 7558Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Robinson Building, Suite B7800, Boston, MA 02118 USA ,grid.189504.10000 0004 1936 7558Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA ,grid.189504.10000 0004 1936 7558Department of Neurosurgery, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA
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Design and Verbal Fluency in Alzheimer's Disease and Frontotemporal Dementia: Clinical and Metabolic Correlates. J Int Neuropsychol Soc 2022; 28:947-962. [PMID: 34569460 DOI: 10.1017/s1355617721001144] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Cognitive processes underlying verbal and design fluency, and their neural correlates in patients with Alzheimer's disease (AD) and behavioural variant Frontotemporal Dementia (bvFTD) remain unclear. We hypothesised that verbal and design fluency may be associated with distinct neuropsychological processes in AD and FTD, showing different patterns of impairment and neural basis. METHODS We enrolled 142 participants including patients with AD (n = 80, mean age = 74.71), bvFTD (n = 34, mean age = 68.18), and healthy controls (HCs) (n = 28, mean age = 71.14), that underwent cognitive assessment and 18F-fluorodeoxyglucose positron emission tomography imaging. RESULTS Semantic and phonemic fluency showed the largest effect sizes between groups, showing lower scores in bvFTD than AD and HCs, and lower scores in AD than HC. Both AD and bvFTD showed a lower number of unique designs in design fluency in comparison to HC. Semantic fluency was correlated with left frontotemporal lobe in AD, and with left frontal, caudate, and thalamus in bvFTD. Percentage of unique designs in design fluency was associated with the metabolism of the bilateral fronto-temporo-parietal cortex in AD, and the bilateral frontal cortex with right predominance in bvFTD. Repetitions in AD were correlated with bilateral frontal, temporal, and parietal lobes, and with left prefrontal cortex in bvFTD. CONCLUSIONS Our findings demonstrate differential underlying cognitive processes in verbal and design fluency in AD and bvFTD. While memory and executive functioning associated with fronto-temporo-parietal regions were key in AD, attention and executive functions correlated with the frontal cortex and played a more significant role in bvFTD during fluency tasks.
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Foster PH, Russell LL, Peakman G, Convery RS, Bouzigues A, Greaves CV, Bocchetta M, Cash DM, van Swieten JC, Jiskoot LC, Moreno F, Sanchez-Valle R, Laforce R, Graff C, Masellis M, Tartaglia C, Rowe JB, Borroni B, Finger E, Synofzik M, Galimberti D, Vandenberghe R, de Mendonça A, Butler CR, Gerhard A, Ducharme S, Le Ber I, Tagliavini F, Santana I, Pasquier F, Levin J, Danek A, Otto M, Sorbi S, Rohrer JD. Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort. Cortex 2022; 150:12-28. [PMID: 35325762 PMCID: PMC9067453 DOI: 10.1016/j.cortex.2022.01.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 12/14/2021] [Accepted: 01/09/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. METHODS Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants from the Genetic FTD Initiative: 216 mutation-negative controls, 192 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. Using global scores from the CDR® plus NACC FTLD, mutation carriers were divided into three groups, asymptomatic (0), very mildly symptomatic/prodromal (.5), or fully symptomatic (1 or more). The mIRI Total score, as well as the subscores of Empathic Concern (EC) and Perspective Taking (PT) were assessed. Linear regression models with bootstrapping were used to assess empathy ratings across genetic groups, as well as across phenotypes in the symptomatic carriers. Neural correlates of empathy deficits were examined using a voxel-based morphometry (VBM) analysis. RESULTS All fully symptomatic groups scored lower on the mIRI Total, EC, and PT when compared to controls and their asymptomatic or prodromal counterparts (all p < .001). Prodromal C9orf72 expansion carriers also scored significantly lower than controls on the mIRI Total score (p = .046). In the phenotype analysis, all groups (behavioural variant FTD, primary progressive aphasia and FTD with amyotrophic lateral sclerosis) scored significantly lower than controls (all p < .007). VBM revealed an overlapping neural correlate of the mIRI Total score across genetic groups in the orbitofrontal lobe but with additional involvement in the temporal lobe, insula and basal ganglia in both the GRN and MAPT groups, and uniquely more posterior regions such as the parietal lobe and thalamus in the GRN group, and medial temporal structures in the MAPT group. CONCLUSIONS Significant empathy deficits present in genetic FTD, particularly in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf72 expansion carriers.
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Affiliation(s)
- Phoebe H Foster
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - Lucy L Russell
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - Georgia Peakman
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - Rhian S Convery
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - Arabella Bouzigues
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - Caroline V Greaves
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - Martina Bocchetta
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
| | - David M Cash
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; Centre for Medical Image Computing, University College London, London, UK
| | | | - Lize C Jiskoot
- Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands
| | - Fermin Moreno
- Cognitive Disorders Unit, Department of Neurology, Donostia Universitary Hospital, San Sebastian, Spain; Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Gipuzkoa, Spain
| | - Raquel Sanchez-Valle
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
| | - Robert Laforce
- Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, QC, Canada
| | - Caroline Graff
- Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet, Solna, Sweden; Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden
| | - Mario Masellis
- Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada
| | - Carmela Tartaglia
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada
| | - James B Rowe
- University of Cambridge Department of Clinical Neurosciences, and University of Cambridge Hospitals NHS Trust, University of Cambridge, UK
| | - Barbara Borroni
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Elizabeth Finger
- Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada
| | - Matthis Synofzik
- Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany; Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
| | - Daniela Galimberti
- Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy
| | - Rik Vandenberghe
- Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium; Neurology Service, University Hospitals Leuven, Leuven, Belgium; Leuven Brain Institute, KU Leuven, Leuven, Belgium
| | | | - Chris R Butler
- Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK; Department of Brain Sciences, Imperial College London, UK
| | - Alex Gerhard
- Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK; Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg-Essen, Germany
| | - Simon Ducharme
- Department of Psychiatry, McGill University Health Centre, McGill University, Montreal, Québec, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada
| | - Isabelle Le Ber
- Sorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Reference Network for Rare Neurological Diseases (ERN-RND)
| | | | - Isabel Santana
- University Hospital of Coimbra (HUC), Neurology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Florence Pasquier
- Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
| | - Johannes Levin
- Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany
| | - Adrian Danek
- Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany
| | - Markus Otto
- Department of Neurology, University of Ulm, Germany
| | - Sandro Sorbi
- Department of Neurofarba, University of Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
| | - Jonathan D Rohrer
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
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7
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Girasek H, Nagy VA, Fekete S, Ungvari GS, Gazdag G. Prevalence and correlates of aggressive behavior in psychiatric inpatient populations. World J Psychiatry 2022; 12:1-23. [PMID: 35111577 PMCID: PMC8783168 DOI: 10.5498/wjp.v12.i1.1] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/18/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Aggressive behavior in patients with psychiatric disorders is attracting increasing research interest. One reason for this is that psychiatric patients are generally considered more likely to be aggressive, which raises a related question of whether diagnoses of psychiatric disorders predict the prevalence of aggressive behavior. Predicting aggression in psychiatric wards is crucial, because aggressive behavior not only endangers the safety of both patients and staff, but it also extends the hospitalization times. Predictions of aggressive behavior also need careful attention to ensure effective treatment planning. This literature review explores the relationship between aggressive behavior and psychiatric disorders and syndromes (dementia, psychoactive substance use, acute psychotic disorder, schizophrenia, bipolar affective disorder, major depressive disorder, obsessive-compulsive disorder, personality disorders and intellectual disability). The prevalence of aggressive behavior and its underlying risk factors, such as sex, age, comorbid psychiatric disorders, socioeconomic status, and history of aggressive behavior are discussed as these are the components that mostly contribute to the increased risk of aggressive behavior. Measurement tools commonly used to predict and detect aggressive behavior and to differentiate between different forms of aggressive behavior in both research and clinical practice are also reviewed. Successful aggression prevention programs can be developed based on the current findings of the correlates of aggressive behavior in psychiatric patients.
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Affiliation(s)
- Hunor Girasek
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
| | - Vanda Adél Nagy
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
| | - Szabolcs Fekete
- Department of Psychiatry, National Institute of Forensic Psychiatry, Budapest 1108, Hungary
- School of PhD Studies, Semmelweis University, Budapest 1085, Hungary
| | - Gabor S Ungvari
- Division of Psychiatry, School of Medicine, University of Western Australia, Crawley 6009, Australia
- Section of Psychiatry, University of Notre Dame, Fremantle 6160, Australia
| | - Gábor Gazdag
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Budapest 1083, Hungary
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8
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Kiosses DN, Pantelides J. Criminal and Socially Inappropriate Behavior as Early Signs of Cognitive Decline. Am J Geriatr Psychiatry 2021; 29:666-668. [PMID: 33423869 DOI: 10.1016/j.jagp.2020.12.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 10/22/2022]
Affiliation(s)
- Dimitris N Kiosses
- Weill-Cornell Institute of Geriatric Psychiatry (DNK, JP), White Plains, NY, USA.
| | - Joanna Pantelides
- Weill-Cornell Institute of Geriatric Psychiatry (DNK, JP), White Plains, NY, USA
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9
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Riello M, Rusconi E, Treccani B. The Role of Brief Global Cognitive Tests and Neuropsychological Expertise in the Detection and Differential Diagnosis of Dementia. Front Aging Neurosci 2021; 13:648310. [PMID: 34177551 PMCID: PMC8222681 DOI: 10.3389/fnagi.2021.648310] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 04/07/2021] [Indexed: 11/13/2022] Open
Abstract
Dementia is a global public health problem and its impact is bound to increase in the next decades, with a rapidly aging world population. Dementia is by no means an obligatory outcome of aging, although its incidence increases exponentially in old age, and its onset may be insidious. In the absence of unequivocal biomarkers, the accuracy of cognitive profiling plays a fundamental role in the diagnosis of this condition. In this Perspective article, we highlight the utility of brief global cognitive tests in the diagnostic process, from the initial detection stage for which they are designed, through the differential diagnosis of dementia. We also argue that neuropsychological training and expertise are critical in order for the information gathered from these omnibus cognitive tests to be used in an efficient and effective way, and thus, ultimately, for them to fulfill their potential.
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Affiliation(s)
- Marianna Riello
- Department of Psychology and Cognitive Science, University of Trento, Trento, Italy
| | - Elena Rusconi
- Department of Psychology and Cognitive Science, University of Trento, Trento, Italy
| | - Barbara Treccani
- Department of Psychology and Cognitive Science, University of Trento, Trento, Italy
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10
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Rouse HJ, Small BJ, Schinka JA, Loewenstein DA, Duara R, Potter H. Mild behavioral impairment as a predictor of cognitive functioning in older adults. Int Psychogeriatr 2021; 33:285-293. [PMID: 32456733 DOI: 10.1017/s1041610220000678] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE To assess the influence of mild behavioral impairment (MBI) on the cognitive performance of older adults who are cognitively healthy or have mild cognitive impairment (MCI). METHODS Secondary data analysis of a sample (n = 497) of older adults from the Florida Alzheimer's Disease Research Center who were either cognitively healthy (n = 285) or diagnosed with MCI (n = 212). Over half of the sample (n = 255) met the operationalized diagnostic criteria for MBI. Cognitive domains of executive function, attention, short-term memory, and episodic memory were assessed using a battery of neuropsychological tests. RESULTS Older adults with MBI performed worse on tasks of executive function, attention, and episodic memory compared to those without MBI. A significant interaction revealed that persons with MBI and MCI performed worse on tasks of episodic memory compared to individuals with only MCI, but no significant differences were found in performance in cognitively healthy older adults with or without MBI on this cognitive domain. As expected, cognitively healthy older adults performed better than individuals with MCI on every domain of cognition. CONCLUSIONS The present study found evidence that independent of cognitive status, individuals with MBI performed worse on tests of executive function, attention, and episodic memory than individuals without MBI. Additionally, those with MCI and MBI perform significantly worse on episodic memory tasks than individuals with only MCI. These results provide support for a unique cognitive phenotype associated with MBI and highlight the necessity for assessing both cognitive and behavioral symptoms.
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Affiliation(s)
- Hillary J Rouse
- School of Aging Studies, University of South Florida, Tampa, FL, USA
| | - Brent J Small
- School of Aging Studies, University of South Florida, Tampa, FL, USA
| | - John A Schinka
- School of Aging Studies, University of South Florida, Tampa, FL, USA
| | - David A Loewenstein
- Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, University of Miami, Miami, FL, USA
| | - Ranjan Duara
- Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, University of Miami, Miami, FL, USA
| | - Huntington Potter
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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11
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Brown CL, Hua AY, De Coster L, Sturm VE, Kramer JH, Rosen HJ, Miller BL, Levenson RW. Comparing two facets of emotion perception across multiple neurodegenerative diseases. Soc Cogn Affect Neurosci 2020; 15:511-522. [PMID: 32363385 PMCID: PMC7328026 DOI: 10.1093/scan/nsaa060] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 03/25/2020] [Accepted: 04/27/2020] [Indexed: 12/30/2022] Open
Abstract
Deficits in emotion perception (the ability to infer others' emotions accurately) can occur as a result of neurodegeneration. It remains unclear how different neurodegenerative diseases affect different forms of emotion perception. The present study compares performance on a dynamic tracking task of emotion perception (where participants track the changing valence of a film character's emotions) with performance on an emotion category labeling task (where participants label specific emotions portrayed by film characters) across seven diagnostic groups (N = 178) including Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), non-fluent variant primary progressive aphasia (nfvPPA), progressive supranuclear palsy (PSP), corticobasal syndrome and healthy controls. Consistent with hypotheses, compared to controls, the bvFTD group was impaired on both tasks. The svPPA group was impaired on the emotion labeling task, whereas the nfvPPA, PSP and AD groups were impaired on the dynamic tracking task. Smaller volumes in bilateral frontal and left insular regions were associated with worse labeling, whereas smaller volumes in bilateral medial frontal, temporal and right insular regions were associated with worse tracking. Findings suggest labeling and tracking facets of emotion perception are differentially affected across neurodegenerative diseases due to their unique neuroanatomical correlates.
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Affiliation(s)
- Casey L Brown
- Berkeley Psychophysiology Laboratory, Department of Psychology, University of California, Berkeley, CA 94720-1650, USA
- Department of Psychiatry, University of California, San Francisco, CA 94115, USA
| | - Alice Y Hua
- Berkeley Psychophysiology Laboratory, Department of Psychology, University of California, Berkeley, CA 94720-1650, USA
| | - Lize De Coster
- Department of Psychiatry, University of California, San Francisco, CA 94115, USA
| | - Virginia E Sturm
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94115, USA
| | - Joel H Kramer
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94115, USA
| | - Howard J Rosen
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94115, USA
| | - Bruce L Miller
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94115, USA
| | - Robert W Levenson
- Berkeley Psychophysiology Laboratory, Department of Psychology, University of California, Berkeley, CA 94720-1650, USA
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12
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Consonni M, Cappa SF, Dalla Bella E, Contarino VE, Lauria G. Cortical correlates of behavioural change in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2019; 90:380-386. [PMID: 30322899 DOI: 10.1136/jnnp-2018-318619] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 09/25/2018] [Accepted: 09/26/2018] [Indexed: 01/15/2023]
Abstract
BACKGROUND Behavioural changes in amyotrophic lateral sclerosis (ALS) are heterogeneous. The study aim was to identify the behavioural profiles of non-demented patients with ALS and their neuroimaging correlates and to elucidate if they are comparable to those reported in studies of the behavioural-variant of frontotemporal dementia (bvFTD). METHODS Behavioural changes of 102 non-demented patients with ALS were assessed through the Frontal Behavioural Inventory (FBI), a 24-item scale assessing different behavioural modifications, mainly chosen from the core clinical features of FTD. Principal component analysis (PCA) was used to detect distinct clusters of behavioural changes based on FBI subscores. The cortical thinning related to each behavioural profile was analysed in 29 patients with ALS. Cronbach's α was used to test the reliability of bvFTD-related FBI clustering in our cohort. RESULTS Sixty patients with ALS had FBI score≥1. PCA identified three phenotypic clusters loading on disinhibited/hostile, dysexecutive and apathetic FBI subscores. Imaging analyses revealed that the thinning of bilateral orbitofrontal cortex was related to apathy, the right frontotemporal and cingular cortex to the disinhibited/hostile profile and the left precuneus cortex to the dysexecutive behaviours. The bvFTD-associated aggressive profile reliably applied to our cohort. CONCLUSIONS In non-demented patients with ALS, different behavioural profiles could be identified. The right frontotemporal and cingular cortex thinning was the hallmark of the behavioural profile mostly overlapping that described in bvFTD. Our findings provide the unbiased identification of determinants relevant for a novel stratification of patients with ALS based on their behavioural impairment, which might be useful as proxy of cognitive decline.
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Affiliation(s)
- Monica Consonni
- 3rd Neurology Unit and Motor Neuron Diseases Centre, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Stefano F Cappa
- Institute for Advanced Study-IUSS Pavia, Pavia, Italy.,IRCCS S. Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Eleonora Dalla Bella
- 3rd Neurology Unit and Motor Neuron Diseases Centre, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Valeria Elisa Contarino
- Department of Neuroradiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuseppe Lauria
- 3rd Neurology Unit and Motor Neuron Diseases Centre, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy .,Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy
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13
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Cheran G, Wu L, Lee S, Manoochehri M, Cines S, Fallon E, Lynch T, Heidebrink J, Paulson H, Goldman J, Huey E, Cosentino S. Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers. J Int Neuropsychol Soc 2019; 25:184-194. [PMID: 30458895 PMCID: PMC6374161 DOI: 10.1017/s1355617718001005] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVES The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. METHODS Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. RESULTS Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. CONCLUSIONS Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184-194).
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Affiliation(s)
- Gayathri Cheran
- Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, NY
| | - Liwen Wu
- Columbia University, Department of Biostatistics, Mailman School of Public Health, New York, NY
| | - Seonjoo Lee
- Columbia University, Department of Biostatistics, Mailman School of Public Health, New York, NY
| | - Masood Manoochehri
- Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, NY
| | - Sarah Cines
- Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, NY
- Fairleigh Dickinson University, Teaneck, NJ
| | - Emer Fallon
- Dublin Neurological Institute, Dublin, Ireland
| | | | | | - Henry Paulson
- The University of Michigan, Department of Neurology, Ann Arbor, MI
| | - Jill Goldman
- Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, NY
| | - Edward Huey
- Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, NY
- Columbia University, Department of Psychiatry & New York State Psychiatric Institute, New York, NY
| | - Stephanie Cosentino
- Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, NY
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14
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Evidence of semantic processing impairments in behavioural variant frontotemporal dementia and Parkinson's disease. Curr Opin Neurol 2018; 30:617-622. [PMID: 28914737 DOI: 10.1097/wco.0000000000000498] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations. Less well understood, however, is how heteromodal semantic hubs work to integrate and process semantic information. RECENT FINDINGS Although the majority of semantic research to date has focused on how sensory cortical areas are important for the representation of semantic features, new research explores how semantic memory is affected by neurodegeneration in regions important for semantic processing. Here, we review studies that demonstrate impairments to abstract noun knowledge in behavioural variant frontotemporal degeneration (bvFTD) and to action verb knowledge in Parkinson's disease, and discuss how these deficits relate to disease of the semantic selection network. SUMMARY Findings demonstrate that semantic selection processes are supported by the left inferior frontal gyrus (LIFG) and basal ganglia, and that disease to these regions in bvFTD and Parkinson's disease can lead to categorical impairments for abstract nouns and action verbs, respectively.
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15
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de Bellis A, de Bellis M, Aloe L. Long-Term Non-Invasive Treatment via Intranasal Administration of Nerve Growth Factor Protects the Human Brain in Frontotemporal Dementia associated with Corticobasal Syndrome: A Pilot Study. J Alzheimers Dis Rep 2018; 2:67-77. [PMID: 30480250 PMCID: PMC6159695 DOI: 10.3233/adr-180055] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Background: Nerve growth factor (NGF) is known for playing a critical protective role on a number of brain neurons in mammals, including humans. NGF can be delivered to the CNS via nasal route and has a neuroprotective action in case of neurodegenerative diseases. Objective: The aim of this study is to investigate for the first time whether purified NGF can play a neuroprotective role on human brain neurons affected by neurodegenerative diseases when administered via nasal route. Methods: Two female patients, both affected by frontotemporal dementia (FTD) associated with corticobasal syndrome (CBS) at different stages of disease progression, received a daily intranasal NGF spray for one year. Clinical/neurological aspects were observed over time. The follow-up study was performed using 18 FDG PET. Results: This case study seems to demonstrate that IN-NGF slows down the common decline caused by FTD/CBS. Conclusions: These findings suggest the potential neuroprotective role of IN-NGF administered in case of neurodegenerative diseases.
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Affiliation(s)
- Alberto de Bellis
- Maria Rosaria Maglione Foundation onlus, Naples/Morra De Sanctis, Italy
| | - Massimo de Bellis
- Maria Rosaria Maglione Foundation onlus, Naples/Morra De Sanctis, Italy
| | - Luigi Aloe
- Institute of Neurobiology and Molecular Medicine, National Research Council (CNR) Rome, Italy
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16
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de la Torre JC. Are Major Dementias Triggered by Poor Blood Flow to the Brain? Theoretical Considerations. J Alzheimers Dis 2018; 57:353-371. [PMID: 28211814 DOI: 10.3233/jad-161266] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP). This process is known to lead to oxidative stress. Virtually all neurodegenerative diseases, including FTD, DLB, and CJD, are characterized by oxidative stress that promotes inclusion bodies which differ in structure, location, and origin, as well as which neurological disorder they typify. Inclusion bodies have one thing in common; they are known to diminish autophagic activity, the protective intracellular degradative process that removes malformed proteins, protein aggregates, and damaged subcellular organelles that can disrupt neuronal homeostasis. Neurons are dependent on autophagy for their normal function and survival. When autophagic activity is diminished or impaired in neurons, high levels of unfolded or misfolded proteins overwhelm and downregulate the neuroprotective activity of unfolded protein response which is unable to get rid of dysfunctional organelles such as damaged mitochondria and malformed proteins at the synapse. The endpoint of this neuropathologic process results in damaged synapses, impaired neurotransmission, cognitive decline, and dementia.
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17
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Diehl-Schmid J, Richard-Devantoy S, Grimmer T, Förstl H, Jox R. Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care. Int J Geriatr Psychiatry 2017; 32:876-881. [PMID: 27374872 DOI: 10.1002/gps.4540] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 06/01/2016] [Accepted: 06/06/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aim of the present study was to gain insight into the living and care situation in advanced behavioral variant frontotemporal dementia (bvFTD), to describe symptoms and findings in advanced bvFTD, and to evaluate somatic comorbidities and circumstances of death. METHODS Standardized interviews were conducted with family caregivers of 83 patients with bvFTD. Forty-four percent of the patients were already deceased at the time of the interview. RESULTS At the time of the interview or death, respectively, 47% of the patients lived in a nursing home. The median time between symptom onset and nursing home admission was 5.0 ± 5.5 years. In moderate and severe dementia stages almost all patients suffered from severe disabilities including impairment of language, gait, swallowing, and of the ability to care for themselves. Sixteen percent of the patients had got enteral tube feeding. Comorbid somatic diseases were diagnosed in 46% of the patients. Twenty-three percent of the deceased patients had been admitted into a hospital before death. Cardiovascular disease and respiratory disease, mostly pneumonia, were the most frequent causes of death. CONCLUSIONS Advanced bvFTD is characterized by severe cognitive impairment and physical disabilities. BvFTD leads to a premature death. Our findings stress the importance of strategies that maximize patient comfort in advanced disease stages and allow for a peaceful death. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- J Diehl-Schmid
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar of Technical University of Munich, Munich, Germany
| | - S Richard-Devantoy
- McGill University, Department of Psychiatry, and Douglas Mental Health University Institute, McGill Group for Suicide Studies, Montréal, Canada.,Hôpital de Saint-Jérôme, CISSS des Laurentides, Saint-Jérôme, Canada, and Laboratoire de Psychologie des Pays de la Loire, Université d'Angers, Angers, France
| | - T Grimmer
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar of Technical University of Munich, Munich, Germany
| | - H Förstl
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar of Technical University of Munich, Munich, Germany
| | - R Jox
- Institute of Ethics, History, and Theory of Medicine, Ludwig Maximilians Universität München, Munich, Germany
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18
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Trojano L, Gainotti G. Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia. J Alzheimers Dis 2017; 53:31-52. [PMID: 27104898 DOI: 10.3233/jad-160009] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing.
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Affiliation(s)
- Luigi Trojano
- Department of Psychology, Second University of Naples, Italy.,S. Maugeri Foundation, Scientific Institute of Telese Terme (BN), Italy
| | - Guido Gainotti
- Center for Neuropsychological Research, Institute of Neurology, Catholic University, Rome, Italy.,IRCCS Fondazione Santa Lucia, Department of Clinical and Behavioral Neurology, Rome, Italy
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Cousins KAQ, Ash S, Irwin DJ, Grossman M. Dissociable substrates underlie the production of abstract and concrete nouns. BRAIN AND LANGUAGE 2017; 165:45-54. [PMID: 27912073 PMCID: PMC5237409 DOI: 10.1016/j.bandl.2016.11.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 09/14/2016] [Accepted: 11/14/2016] [Indexed: 05/20/2023]
Affiliation(s)
- Katheryn A Q Cousins
- Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, United States.
| | - Sharon Ash
- Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, United States
| | - David J Irwin
- Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, United States
| | - Murray Grossman
- Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, United States.
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Fernández Suarez M, Surace E, Harris P, Tapajoz F, Sevlever G, Allegri R, Russo GN. C9ORF72 G4C2-repeat expansion and frontotemporal dementia first reported case in Argentina. Neurocase 2016; 22:281-4. [PMID: 27327087 DOI: 10.1080/13554794.2016.1186700] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We present a female patient aged 51 who developed behavioral disorders followed by cognitive impairment over 3 years. Neuropsychological, neuropsychiatric, and radiological features suggested a probable behavioral variant of frontotemporal dementia (bvFTD). A family history of amyotrophic lateral sclerosis and parkinsonism suggested the hexanucleotide repeat expansion G4C2 in C9ORF72 . We set up a two-step genotyping algorithm for the detection of the expansion using fragment-length analysis polymerase chain reaction (PCR) and repeat-primed PCR with fluorescent primers. We confirmed the presence of an expanded G4C2 allele in the patient. This represents the first documented case of bvFTD due to a C9ORF72 expansion in Argentina.
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Affiliation(s)
- M Fernández Suarez
- a Neurology and Neurosurgery Unit , Swiss Medical, Sanatorio de los Arcos , Buenos Aires , Argentina
| | - Ezequiel Surace
- b Neuropathology and Molecular Biology Department , Instituto de Investigaciones Neurológica "Raúl Carrea" (FLENI) , Buenos Aires , Argentina.,c Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Argentina
| | - P Harris
- c Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Argentina.,d Cognitive and Neuropsychology Unit , Instituto de Investigaciones Neurológica "Raúl Carrea" (FLENI) , Buenos Aires , Argentina
| | - F Tapajoz
- c Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Argentina.,d Cognitive and Neuropsychology Unit , Instituto de Investigaciones Neurológica "Raúl Carrea" (FLENI) , Buenos Aires , Argentina
| | - G Sevlever
- b Neuropathology and Molecular Biology Department , Instituto de Investigaciones Neurológica "Raúl Carrea" (FLENI) , Buenos Aires , Argentina
| | - R Allegri
- c Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Argentina.,d Cognitive and Neuropsychology Unit , Instituto de Investigaciones Neurológica "Raúl Carrea" (FLENI) , Buenos Aires , Argentina
| | - G N Russo
- a Neurology and Neurosurgery Unit , Swiss Medical, Sanatorio de los Arcos , Buenos Aires , Argentina
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Ranasinghe KG, Rankin KP, Lobach IV, Kramer JH, Sturm VE, Bettcher BM, Possin K, Christine You S, Lamarre AK, Shany-Ur T, Stephens ML, Perry DC, Lee SE, Miller ZA, Gorno-Tempini ML, Rosen HJ, Boxer A, Seeley WW, Rabinovici GD, Vossel KA, Miller BL. Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage. Neurology 2016; 86:600-10. [PMID: 26802093 DOI: 10.1212/wnl.0000000000002373] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 10/19/2015] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease. METHODS We examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of patients with bvFTD (n = 204) across progressive stages of disease as measured by the Clinical Dementia Rating (CDR). We also compared cognitive and neuropsychiatric impairments of patients with bvFTD to those of an age-matched cohort with Alzheimer disease (AD) dementia (n = 674). RESULTS At the earliest stage (CDR = 0.5), patients with bvFTD had profound neuropsychiatric disturbances, insensitivity to errors, slower response times, and poor naming, with intact attention span, memory, and facial affect naming. Tests continuing to show progressive, statistically significant stepwise declines after the CDR = 1 stage included free recall, visuoconstruction, set-shifting, error insensitivity, semantic fluency, design fluency, emotion naming, calculations, confrontation naming, syntax comprehension, and verbal agility. At CDR = 0.5, patients with bvFTD significantly outperformed patients with AD in episodic memory and were faster in set-shifting, while scoring quantitatively worse in lexical fluency, emotion naming, and error sensitivity. The overall rate of disease progression in bvFTD was more rapid than in AD. CONCLUSION There are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients.
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Affiliation(s)
- Kamalini G Ranasinghe
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Katherine P Rankin
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
| | - Iryna V Lobach
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Joel H Kramer
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Virginia E Sturm
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Brianne M Bettcher
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Katherine Possin
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - S Christine You
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Amanda K Lamarre
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Tal Shany-Ur
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Melanie L Stephens
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - David C Perry
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Suzee E Lee
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Zachary A Miller
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Maria L Gorno-Tempini
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Howard J Rosen
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Adam Boxer
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - William W Seeley
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Gil D Rabinovici
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Keith A Vossel
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
| | - Bruce L Miller
- From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA
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Kalapatapu RK, Delucchi KL, Wang S, Harbison JD, Nelson EE, Kramer JH. Substance use history in behavioral-variant frontotemporal dementia versus primary progressive aphasia. J Addict Dis 2015; 35:36-41. [PMID: 26485480 PMCID: PMC4720534 DOI: 10.1080/10550887.2015.1102026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
As older adults are prone to cognitive disorders, the interaction of the fields of substance use and misuse and cognitive neuroscience is an emerging area of research. Substance use has been reported in some subtypes of frontotemporal dementia, such as behavioral variant frontotemporal dementia. However, characterization of substance use in other subtypes of frontotemporal dementia, such as primary progressive aphasia, is unknown. The objective of this baseline analysis was to explore whether any measures of substance use history differed significantly among behavioral variant frontotemporal dementia (n = 842) and primary progressive aphasia (n = 526) in a large national dataset. The National Alzheimer's Coordinating Center's Uniform Data Set study is a national dataset that collects data on patients with various cognitive disorders and includes some questions on substance use. Each substance use variable was used as the outcome and the frontotemporal dementia subtype as the predictor. Total years smoked cigarettes, age when last smoked cigarettes, average number of packs/day smoked when participants smoked, and any recent, remote, or combined recent/remote history of alcohol abuse or drug abuse did not significantly differ between the behavioral variant frontotemporal dementia and primary progressive aphasia subtypes (all p-values > .001). A significantly greater percentage of participants smoked in the last 30 days in the behavioral variant frontotemporal dementia subtype (10.4%, n = 834) compared to the primary progressive aphasia subtype (3.3%, n = 517; p < .001). Clinical providers in both the dementia and substance use fields are encouraged to screen for and monitor substance use in all frontotemporal dementia subtypes.
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Affiliation(s)
- Raj K. Kalapatapu
- Department of Psychiatry, University of California, San Francisco, CA, USA
- San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
- San Francisco General Hospital, San Francisco, CA, USA
| | - Kevin L. Delucchi
- Department of Psychiatry, University of California, San Francisco, CA, USA
| | - Sophia Wang
- Department of Psychiatry, Indiana University, Center for Health Innovation and Implementation Science, Indianapolis, IN, USA
| | - John D. Harbison
- Department of Psychiatry, University of California, San Francisco, CA, USA
- San Francisco General Hospital, San Francisco, CA, USA
| | - Emily E. Nelson
- Department of Psychiatry, University of California, San Francisco, CA, USA
- San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
| | - Joel H. Kramer
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA
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Striatal Atrophy in the Behavioural Variant of Frontotemporal Dementia: Correlation with Diagnosis, Negative Symptoms and Disease Severity. PLoS One 2015; 10:e0129692. [PMID: 26075893 PMCID: PMC4468218 DOI: 10.1371/journal.pone.0129692] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 05/12/2015] [Indexed: 11/19/2022] Open
Abstract
Introduction Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition. Materials and Methods Magnetic resonance imaging scans from 28 patients with bvFTD and 26 healthy controls were manually traced using image analysis software (ITK-SNAP). The resulting 3-D objects underwent volumetric analysis and shape analysis, through spherical harmonic description with point distribution models (SPHARM-PDM). Correlations with size and shape were sought with clinical measures in the bvTFD group, including Frontal Behavioural Inventory, Clinical Dementia Rating for bvFTD, Color Word Interference, Hayling part B and Brixton tests, and Trail-Making Test. Results Caudate nuclei and putamina were significantly smaller in the bvFTD group compared to controls (left caudate 16% smaller, partial eta squared 0.173, p=0.003; right caudate 11% smaller, partial eta squared 0.103, p=0.023; left putamen 18% smaller, partial eta squared 0.179, p=0.002; right putamen 12% smaller, partial eta squared 0.081, p=0.045), with global shape deflation in the caudate bilaterally but no localised shape change in putamen. In the bvFTD group, shape deflations on the left, corresponding to afferent connections from dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity. Global shape deflation in the putamen correlated with Frontal Behavioural Inventory scores—higher scoring on negative symptoms was associated with the left putamen, while positive symptoms were associated with the right. Other cognitive tests had poor completion rates. Conclusion Behavioural symptoms and severity of bvFTD are correlated with abnormalities in striatal size and shape. This adds to the promise of imaging the striatum as a biomarker in this disease.
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Castro-Chavira SA, Fernandez T, Nicolini H, Diaz-Cintra S, Prado-Alcala RA. Genetic markers in biological fluids for aging-related major neurocognitive disorder. Curr Alzheimer Res 2015; 12:200-9. [PMID: 25731625 PMCID: PMC4443795 DOI: 10.2174/1567205012666150302155138] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Revised: 01/18/2015] [Accepted: 01/20/2015] [Indexed: 12/11/2022]
Abstract
Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer' s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders.
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Affiliation(s)
| | | | | | | | - R A Prado-Alcala
- Departamento de Neurobiologia Conductual y Cognitiva, Instituto de Neurobiologia, Campus UNAM Juriquilla, Universidad Nacional Autonoma de Mexico, Boulevard Universitario # 3001, Juriquilla, Queretaro. C. P. 76230, Queretaro, Mexico.
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Lemos R, Duro D, Simões MR, Santana I. The free and cued selective reminding test distinguishes frontotemporal dementia from Alzheimer's disease. Arch Clin Neuropsychol 2014; 29:670-9. [PMID: 25062746 DOI: 10.1093/arclin/acu031] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Memory impairment is often present in frontotemporal dementia (FTD) as a result of an inefficient use of learning strategies, sometimes leading to a misdiagnosis of Alzheimer's disease (AD). The Free and Cued Selective Reminding Test (FCSRT) is a memory test that controls attention and acquisition, by providing category cues in the learning process. The main goal of this study was to show the usefulness of the FCSRT in the distinction between behavioral (bv-) FTD and AD. Three matched subgroups of participants were considered: bv-FTD (n = 32), AD (n = 32), and a control group of healthy adults (n = 32). Results proved that while AD patients exhibited an overall impairment in FCSRT, bv-FTD subjects showed to benefit more from the controlled learning through category cues. AD patients were 25 times more likely to have an impaired FCSRT. The FCSRT has shown its utility in the distinction between bv-FTD and AD, therefore increasing the diagnostic accuracy.
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Affiliation(s)
- Raquel Lemos
- Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal Visual Neuroscience Laboratory, Institute of Biomedical Research in Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Diana Duro
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal Neurology Department of the Coimbra Hospital and University Center, Coimbra, Portugal
| | - Mário R Simões
- Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal
| | - Isabel Santana
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal Neurology Department of the Coimbra Hospital and University Center, Coimbra, Portugal
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Narme P, Mouras H, Roussel M, Devendeville A, Godefroy O. Assessment of socioemotional processes facilitates the distinction between frontotemporal lobar degeneration and Alzheimer’s disease. J Clin Exp Neuropsychol 2013; 35:728-44. [DOI: 10.1080/13803395.2013.823911] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Poletti M, Enrici I, Adenzato M. Cognitive and affective Theory of Mind in neurodegenerative diseases: Neuropsychological, neuroanatomical and neurochemical levels. Neurosci Biobehav Rev 2012; 36:2147-64. [DOI: 10.1016/j.neubiorev.2012.07.004] [Citation(s) in RCA: 146] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2012] [Revised: 06/25/2012] [Accepted: 07/11/2012] [Indexed: 12/14/2022]
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Abstract
Participants diagnosed with mild cognitive impairment (MCI), dementia and controls completed measures that required decoding emotions from point-light displays of bodily motion, and static images of facial affect. Both of these measures tap social cognitive processes that are considered critical for social competency. Consistent with prior literature, both clinical groups were impaired on the static measure of facial affect recognition. The dementia (but not the MCI) group additionally showed difficulties interpreting biological motion cues. However, this did not reflect a specific deficit in decoding emotions, but instead a more generalized difficulty in processing visual motion (both to action and to emotion). These results align with earlier studies showing that visual motion processing is disrupted in dementia, but additionally show for the first time that this extends to the recognition of socially relevant biological motion. The absence of any MCI related impairment on the point-light biological emotion measure (coupled with deficits on the measure of facial affect recognition) also point to a potential disconnect between the processes implicated in the perception of emotion cues from static versus dynamic stimuli. For clinical (but not control) participants, performance on all recognition measures was inversely correlated with level of semantic memory impairment. (JINS, 2012, 18, 1-8).
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29
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The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia. J Int Neuropsychol Soc 2012; 18:834-44. [PMID: 22835330 PMCID: PMC3620020 DOI: 10.1017/s1355617712000604] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).
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Looi JCL, Walterfang M, Velakoulis D, Macfarlane MD, Svensson LA, Wahlund LO. Frontotemporal dementia as a frontostriatal disorder: neostriatal morphology as a biomarker and structural basis for an endophenotype. Aust N Z J Psychiatry 2012; 46:422-34. [PMID: 22535292 DOI: 10.1177/0004867411432076] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This article reviews the evidence for a re-conceptualisation of a subtype of frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), as a frontostriatal disorder, working towards an endophenotype. METHOD We provide an overview of the role of frontostriatal circuits relevant to FTLD and FTD, as a subset of larger-scale distributed brain networks. We discuss the role of a strategic structure in these circuits, the neostriatum. Then we review the relationship of the clinical features of FTLD to frontostriatal circuits, correlating this with neuropsychological and neuropathological data. CONCLUSION The unique structure and linkages of the neostriatum make it an ideal structure for in vivo neuroimaging to understand the neuroanatomical basis of FTD. We develop a frontostriatal endophenotypic model for FTD as a platform for further investigation.
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Affiliation(s)
- Jeffrey C L Looi
- Research Centre for the Neurosciences of Ageing, Academic Unit of Psychological Medicine, Australian National University Medical School, Canberra Hospital, Canberra, Australia.
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Duval C, Bejanin A, Piolino P, Laisney M, de La Sayette V, Belliard S, Eustache F, Desgranges B. Theory of mind impairments in patients with semantic dementia. Brain 2012; 135:228-41. [PMID: 22232593 DOI: 10.1093/brain/awr309] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Semantic dementia is characterized by semantic deficits and behavioural abnormalities that occur in the wake of bilateral inferolateral and predominantly left-sided anterior temporal lobe atrophy. The temporal poles have been shown to be involved in theory of mind, namely the ability to ascribe cognitive and affective mental states to others that regulates social interactions by predicting and interpreting human behaviour. However, very few studies have examined theory of mind in semantic dementia. In this study, we investigated both cognitive and affective theory of mind in a group of patients with semantic dementia, using separate objective and subjective assessment tasks. Results provided objective evidence of an impact of semantic dementia on cognitive and affective theory of mind, consistent with the patients' atrophy in the left temporal lobe and hypometabolism in the temporal lobes and the medial frontal cortex. However, the subjective assessment of theory of mind suggested that awareness of the affective but not cognitive theory of mind deficit persists into the moderate stage of the disease.
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Affiliation(s)
- Céline Duval
- Inserm – EPHE – University of Caen/Basse-Normandie, Unit U923, GIP Cyceron, CHU Côte de Nacre, Caen, France
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Lee SE, Seeley WW, Poorzand P, Rademakers R, Karydas A, Stanley CM, Miller BL, Rankin KP. Clinical characterization of bvFTD due to FUS neuropathology. Neurocase 2012; 18:305-17. [PMID: 22060063 PMCID: PMC3288419 DOI: 10.1080/13554794.2011.604637] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
In 2009, inclusions containing the fused in sarcoma (FUS) protein were identified as a third major molecular class of pathology underlying the behavioral variant frontotemporal dementia (bvFTD) syndrome. Due to the low prevalence of FUS pathology, few clinical descriptions have been published and none provides information about specific social-emotional deficits despite evidence for severe behavioral manifestations in this disorder. We evaluated a patient with bvFTD due to FUS pathology using a comprehensive battery of cognitive and social- emotional tests. A structural MRI scan and genetic tests for tau, progranulin, and FUS mutations were also performed. The patient showed preserved general cognitive functioning and superior working memory, but severe deficits in emotion attribution, sensitivity to punishment, and diminished capacity for interpersonal warmth and empathy. The gray matter atrophy pattern corresponded to this focal deficit profile, with preservation of dorsolateral fronto-parietal regions associated with executive functioning but severe damage to right worse than left frontoinsula, temporal pole, subgenual anterior cingulate, medial orbitofrontal cortex, amygdala, and caudate. This patient demonstrates the striking focality associated with FUS neuropathology in patients with bvFTD.
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Affiliation(s)
- Suzee E Lee
- University of California, San Francisco, Memory and Aging Center, San Francisco, CA 94143-1207, USA
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33
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Immordino-Yang MH, Singh V. Hippocampal contributions to the processing of social emotions. Hum Brain Mapp 2011; 34:945-55. [PMID: 22012639 DOI: 10.1002/hbm.21485] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2011] [Revised: 08/19/2011] [Accepted: 09/12/2011] [Indexed: 11/10/2022] Open
Abstract
Inducing and experiencing emotions about others' mental and physical circumstances is thought to involve self-relevant processing and personal memories of similar experiences. The hippocampus is important for self-referential processing during recall and prospection; however, its contributions during social emotions have not been systematically investigated. We use event-related averaging and Granger causal connectivity mapping to investigate hippocampal contributions during the processing of varieties of admiration and compassion pertaining to protagonists' mental versus physical circumstances [admiration for virtue (AV) versus for skill; compassion for social/psychological pain (CSP) versus for physical pain]. Data were collected using a multistep emotion-induction paradigm that included psychosocial interviews, BOLD fMRI, and simultaneous psychophysiological recording. Given that mnemonic demands were equivalent among conditions, we tested whether: (1) the hippocampi would be recruited more strongly and for a longer duration during the processing of AV and CSP; and (2) connectivity between the hippocampi and cortical systems involved in visceral somatosensation/emotional feeling, social cognitive, and self-related processing would be more extensive during AV and CSP. Results elucidate the hippocampus' facilitative role in inducing and sustaining appropriate emotional reactions, the importance of self-related processing during social emotions, and corroborate the conception that varieties of emotional processing pertaining to others' mental and physical situations engage at least partially distinct neural mechanisms.
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Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EGP, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134:2456-77. [PMID: 21810890 PMCID: PMC3170532 DOI: 10.1093/brain/awr179] [Citation(s) in RCA: 3585] [Impact Index Per Article: 256.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Revised: 05/25/2011] [Accepted: 06/13/2011] [Indexed: 12/20/2022] Open
Abstract
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
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Affiliation(s)
- Katya Rascovsky
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 3 West Gates, Philadelphia, PA 19104, USA.
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35
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Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EGP, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. BRAIN : A JOURNAL OF NEUROLOGY 2011. [PMID: 21810890 DOI: 10.1093/brain/awr179.] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
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Affiliation(s)
- Katya Rascovsky
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 3 West Gates, Philadelphia, PA 19104, USA.
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Abstract
SUMMARY Before dementia becomes manifest, it is preceded by a long period during which neuropathology exists without clinical symptoms, termed the prodromal stage of dementia (ProD). Owing to its relevance for clinical and research aspects, many efforts are being made to define, diagnose and investigate ProD in greater detail. The ProD state has often been studied in Alzheimer’s disease (AD), whereas less is known about the prodromes of the vascular, extrapyramidal and frontotemporal dementias. Since the operational criteria of ProD are unclear, many studies act on the assumption that ProD and mild cognitive impairment are equivalent concepts. However, owing to several methodological problems with the mild cognitive impairment construct, the viewpoint taken here is that ProD can be understood more profoundly in cohorts of normal elderly subjects. This article discusses the neuropsychological findings of longitudinal, population-based studies, which included elderly, normal subjects, who were followed for years, and made case–control comparisons. Neuropsychological findings clearly revealed deficits in cases (subjects who developed dementia later, mostly AD), which were present already at baseline. Cognitive abnormalities were apparent in the domains of episodic memory, but also in tasks tapping executive, psychomotor and visuospatial functions, attention and naming. Although subtle, these impairments were significant at the group level and often demonstrated deterioration to dementia. Early cognitive deficits of the ProD stage therefore represent markers for the identification of incident AD. It is concluded that neuropsychology is a useful method to screen subjects for ProD at an early time point, when individuals are still normally functioning.
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Affiliation(s)
- Thomas Benke
- Clinic of Neurology, Medical University Innsbruck, Austria
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Leyton CE, Hodges JR. Frontotemporal dementias: Recent advances and current controversies. Ann Indian Acad Neurol 2011; 13:S74-80. [PMID: 21369422 PMCID: PMC3039165 DOI: 10.4103/0972-2327.74249] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2010] [Accepted: 07/25/2010] [Indexed: 12/12/2022] Open
Abstract
Frontotemporal dementia (FTD) syndromes comprise a heterogeneous group of neurodegenerative conditions characterized by atrophy in the frontal and temporal lobes. Three main clinical variants are recognized: Behavioral variant (bv-FTD), Semantic dementia (SD), and Progressive nonfluent aphasia (PNFA). However, logopenic/phonological (LPA) variant has been recently described, showing a distinctive pattern of brain atrophy and often associated to Alzheimer's disease pathology. The diagnosis of FTD is challenging, since there is clinical, pathological, and genetic overlap between the variants and other neurodegenerative diseases, such as motoneuron disease (MND) and corticobasal degeneration (CBD). In addition, patients with gene mutations (tau and progranulin) display an inconsistent clinical phenotype and the correspondence between the clinical variant and its pathology is unpredictable. New cognitive tests based on social cognition and emotional recognition together with advances in molecular pathology and genetics have contributed to an improved understanding. There is now a real possibility of accurate biomarkers for early diagnosis. The present review concentrates on new insights and debates in FTD.
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Affiliation(s)
- Cristian E Leyton
- Neuroscience Research Australia (NeuRA), The University of New South Wales, Sydney, Australia
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Krueger CE, Laluz V, Rosen HJ, Neuhaus JM, Miller BL, Kramer JH. Double dissociation in the anatomy of socioemotional disinhibition and executive functioning in dementia. Neuropsychology 2011; 25:249-59. [PMID: 21381829 DOI: 10.1037/a0021681] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To determine whether socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobes, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. METHOD Subjects included 157 patients with neurodegenerative disease. A semiautomated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including 3 tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single-factor score to represent EF. RESULTS Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, Mini-Mental State Examination, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition, and MFG significantly predicted EF performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. CONCLUSIONS These results support a specific association between orbitofrontal areas and behavioral management as compared with dorsolateral areas and EF.
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Affiliation(s)
- Casey E Krueger
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA.
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Edelstein K, Spiegler BJ, Fung S, Panzarella T, Mabbott DJ, Jewitt N, D'Agostino NM, Mason WP, Bouffet E, Tabori U, Laperriere N, Hodgson DC. Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes. Neuro Oncol 2011; 13:536-45. [PMID: 21367970 PMCID: PMC3093335 DOI: 10.1093/neuonc/nor015] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2010] [Accepted: 01/11/2011] [Indexed: 12/22/2022] Open
Abstract
Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18-47 years]; median time since diagnosis, 15.5 years [range, 6.5-42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.
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Affiliation(s)
- Kim Edelstein
- Psychosocial Oncology and Palliative Care, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON, Canada.
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Onyike CU, Sloane KL, Smyth SF, Appleby BS, Blass DM, Rabins PV. Estimating severity of illness and disability in Frontotemporal Dementia: Preliminary analysis of the Dementia Disability Rating (DDR). ACTA NEUROPSYCHOLOGICA 2011; 9:141-153. [PMID: 24478794 PMCID: PMC3903383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
BACKGROUND Current measures of severity and disability do not stage or track the progression of disability in frontotemporal dementia (FTD) well. We investigated the reliability of the newly developed Dementia Disability Rating (DDR) in the measurement and staging of illness severity in FTD and dementia of the Alzheimer type (DAT). MATERIAL/ METHODS We studied 48 consecutive patients of the Johns Hopkins FTD and Young-Onset Dementias Clinic, with diagnoses of DAT, FTD, vascular dementia and "other" cognitive disorder (CDNOS). Cases were scored on the CDR and DDR by three trained raters, based on neuropsychiatric examinations performed at first visit and other assessments performed within the preceding year. Consensus ratings were assigned in conference. RESULTS Inter-rater correlations of DDR sum of ranks scores for DAT ranged from 0.88 to 0.91, for FTD 0.89-0.96 and for CDNOS 0.85-0.97. Similar correlations were observed of the CDR sum of rank scores for DAT and FTD. Correlations of DDR summary scores for DAT were 0.67-0.91 and for FTD 0.79-0.91, as compared to CDR data: 0.87-0.92 (p<0.0001) and 0.80-0.93 (p<0.0001) for DAT and FTD respectively. In DAT patients the correlation between CDR and DDR summary scores was higher than in FTD patients, whereas correlations based on sum of ranks scores were high in both groups. CONCLUSIONS These preliminary data indicate the DDR measures disability in DAT and FTD, with reliability comparable to the CDR. Convergent validity was demonstrated for the DDR.
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Affiliation(s)
- Chiadi U. Onyike
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
| | - Kelly L. Sloane
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
| | - Shawn F. Smyth
- Division of Movement Disorders, Department of Neurology, Johns Hopkins University School of Medicine
| | - Brian S. Appleby
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
| | - David M. Blass
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
- Abarbanel Mental Health Centre, Bat Yam, Israel
| | - Peter V. Rabins
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
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42
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Abstract
The purpose of this review is to provide a comprehensive update on the genetic causes of frontotemporal lobar degeneration (FTLD). Approximately 40% to 50% of patients diagnosed with FTLD have a family history of a ''related disorder,'' whereas 10% to 40% have an autosomal dominant family history for the disease. At this time, mutations occurring in 2 independent genes located on the same chromosome (MAPT and GRN) have been shown to cause the majority of cases of autosomal dominant FTLD. Specific genetic, molecular, pathological, and phenotypic variations associated with each of these gene mutations are discussed, as well as markers that may help differentiate the 2. In addition, 3 relatively rare, additional genes known to cause familial FTLD are examined in brief. Lastly, genetic counseling issues which may be important to the community clinician are discussed.
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Affiliation(s)
- Tricia M See
- Memory and Aging Center, University of California San Francisco, CA 94143, USA
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43
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Advanced practice nursing: meeting the caregiving challenges for families of persons with frontotemporal dementia. CLIN NURSE SPEC 2010; 24:245-51. [PMID: 20716977 DOI: 10.1097/nur.0b013e3181ecdc32] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Frontotemporal dementia (FTD), once thought to be a rare cause for dementia, is now acknowledged to be the most common presenile (before age 65 years) cause of dementia. Frontotemporal dementia is associated with profound changes in behavior, personality, emotions, and cognition. The purpose of this article is to describe 2 cases of patients with FTD to illustrate salient aspects of the caregiving experience. Issues faced by caregivers are organized into 6 categories: diagnosis, behavioral symptoms, function, communication, long-term management and care, and maintenance of the caregiver's emotional and physical health. Examples of interventions directed by advanced practice nurses are described. We suggest that management of FTD requires expertise as scientific advances and discoveries about FTD continually change the landscape of care.
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Meier SL, Charleston AJ, Tippett LJ. Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis. Brain 2010; 133:3444-57. [PMID: 20889583 DOI: 10.1093/brain/awq254] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis without dementia, some with no signs of dysfunction in tasks sensitive to other regions of prefrontal cortex. This demonstration of variability in cognitive integrity supports previous research indicating amyotrophic lateral sclerosis is a heterogeneous disease.
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Affiliation(s)
- Sandra L Meier
- Department of Psychology, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
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45
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Abstract
Patients with memory disorders have severely restricted learning and memory. For instance, patients with anterograde amnesia can learn motor procedures and retain some restricted ability to learn new words and factual information. However, such learning is inflexible and frequently inaccessible to conscious awareness. Here we present a case of patient AC596, a 25-year-old male with severe episodic memory impairments, presumably due to anoxia during a preterm birth. In contrast to his poor episodic memory, he exhibits savant-like memory for calendar information that can be flexibly accessed by day, month, and year cues. He also has the ability to recollect the exact date of a wide range of personal experiences over the past 20 years. The patient appears to supplement his generally poor episodic memory by using memorized calendar information as a retrieval cue for autobiographical events. These findings indicate that islands of preserved memory functioning, such as a highly developed semantic memory system, can exist in individuals with severely impaired episodic memory systems. In this particular case, our patient's memory for dates far outstripped that of normal individuals and served as a keen retrieval cue, allowing him to access information that was otherwise unavailable.
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Affiliation(s)
- Ingrid R Olson
- Department of Psychology, Temple University, Philadelphia, PA 19122, USA.
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46
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Abstract
The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine-rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN.
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Affiliation(s)
- Andrew Bateman
- Endocrine Research Laboratory, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada.
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47
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Mathias JL, Morphett K. Neurobehavioral differences between Alzheimer's disease and frontotemporal dementia: a meta-analysis. J Clin Exp Neuropsychol 2010; 32:682-98. [PMID: 20063255 DOI: 10.1080/13803390903427414] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The differential diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) remains a difficult clinical issue. A recent meta-analysis by Hutchinson and Mathias (2007) found that many cognitive tests do not adequately differentiate between these types of dementia. However, their study did not examine the ability of neurobehavioral scales to distinguish between AD and FTD. The data from 33 studies, published between January 1994 and December 2008, examining the neurobehavioral symptoms of persons with AD (N = 2,305) and FTD (N = 971) were therefore analyzed. Weighted Cohen's d effect sizes, percentage overlap statistics, confidence intervals, and fail-safe Ns were calculated for each scale. The most discriminating measures were the Schedules for Clinical Assessment in Neuropsychiatry and the Scale for Emotional Blunting. The Middelheim Frontality Score and the Frontal Behavior Inventory also had excellent discriminative ability, surpassing the cognitive tests examined previously. Numerous other scales additionally showed large and significant differences between the AD and FTD groups, highlighting the importance of assessing neurobehavioral symptoms in this context. While these latter measures may be useful in providing a clinical profile of patients with dementia, greater overlap in the scores of patients with AD and FTD limits their usefulness in the context of differential diagnosis.
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Affiliation(s)
- Jane L Mathias
- School of Psychology, University of Adelaide, Adelaide, Australia.
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48
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Suárez J, Tartaglia MC, Vitali P, Erbetta A, Neuhaus J, Laluz V, Miller BL. Characterizing radiology reports in patients with frontotemporal dementia. Neurology 2009; 73:1073-4. [PMID: 19786700 DOI: 10.1212/wnl.0b013e3181b9c8a6] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- J Suárez
- University of Puerto Rico School of Medicine
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49
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Krueger CE, Bird AC, Growdon ME, Jang JY, Miller BL, Kramer JH. Conflict monitoring in early frontotemporal dementia. Neurology 2009; 73:349-55. [PMID: 19652138 DOI: 10.1212/wnl.0b013e3181b04b24] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Despite the extensive frontal atrophy and behavioral disinhibition that characterizes behavioral variant frontotemporal dementia (bvFTD), many studies of early bvFTD suggest normal executive functioning (EF). The current study examined cognitive control in patients with bvFTD who otherwise seemed cognitively normal. METHODS Subjects included 7 patients with bvFTD with normal neuropsychological test scores, 7 patients with bvFTD matched for Mini-Mental State Examination score but with impaired neuropsychological test scores, and 14 normal controls. A flanker paradigm and other measures of EF were administered to participants. A semiautomated parcellation program was used to analyze structural MRI scans. RESULTS On the flanker task, multivariate analysis of variance revealed a significant condition X diagnosis interaction. Both bvFTD groups showed a larger congruency effect than normal controls, i.e., they displayed disproportionately reduced speed and accuracy on incongruent trials relative to congruent trials. Imaging data illustrated significant orbitofrontal atrophy in patients with early bvFTD as compared with controls. CONCLUSIONS Patients with behavioral variant frontotemporal dementia (bvFTD) who performed within normal limits on clinical tests of executive functioning demonstrated a select impairment on an experimental test of cognitive control, suggesting a subtle impairment in inhibiting attention or response to the irrelevant stimuli. Measures of neuropsychological functioning sensitive to the ventromedial prefrontal cortex may be useful in early diagnosis of patients with bvFTD. Our understanding of this syndrome may be increased by considering the efficiency of selective inhibition, a fundamental component of executive cognitive control.
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Affiliation(s)
- C E Krueger
- Memory and Aging Center, UCSF Department of Neurology, San Francisco, CA, USA.
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50
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Henry JD, Thompson C, Ruffman T, Leslie F, Withall A, Sachdev P, Brodaty H. Threat perception in mild cognitive impairment and early dementia. J Gerontol B Psychol Sci Soc Sci 2009; 64:603-7. [PMID: 19671637 DOI: 10.1093/geronb/gbp064] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Mild cognitive impairment (MCI) and dementia affect many aspects of emotion processing. Even though the ability to detect threat is a particularly important aspect of emotion processing, no study to date has assessed threat perception in either of these groups. The purpose of the present study was to test whether individuals with MCI (n = 38) and mild dementia (n = 34) have difficulty differentiating between faces and situations normatively judged to be either high or low in threat relative to age-matched controls (n = 34). To achieve this aim, all participants completed 2 danger rating tasks that involved viewing and rating high- and low-danger images. It was also assessed whether threat perception was related to cognitive functioning and emotion recognition. The results indicated that all 3 groups were accurately, and comparably, able to differentiate high from low-danger faces. However, the dementia group had difficulties differentiating high from low-danger situations, which reflected a bias to overattribute the level of threat posed by normatively judged nonthreatening situations. This difficulty was related to more general cognitive decline.
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Affiliation(s)
- Julie D Henry
- School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia.
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