Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2017; 8(6): 286-296
Published online Jun 15, 2017. doi: 10.4239/wjd.v8.i6.286
Statin use and cognitive function in middle-aged adults with type 1 diabetes
Karen A Nunley, Trevor J Orchard, Christopher M Ryan, Rachel Miller, Tina Costacou, Caterina Rosano
Karen A Nunley, Trevor J Orchard, Christopher M Ryan, Rachel Miller, Tina Costacou, Caterina Rosano, Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213, United States
Author contributions: Nunley KA, Orchard TJ, Costacou T and Rosano C contributed to study conception and design; Nunley KA, Ryan CM, Miller R and Costacou T contributed to data acquisition, analysis, and interpretation; Nunley KA, Orchard TJ, Ryan CM, Miller R, Costacou T and Rosano C contributed to writing, editing, reviewing, and final approval of manuscript.
Supported by National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) grants, Nos. R01 DK089028, PI (to Rosano C); R37 DK034818-25, PI (to Orchard TJ); and R21 DK082900, PI (to Costacou T).
Institutional review board statement: The study was reviewed and approved by the University of Pittsburgh Institutional Review Board.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No authors report a conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Karen A Nunley, PhD, MS, Visiting Assistant Research Professor, Department of Epidemiology, University of Pittsburgh, 5138 South Parran Hall, 130 N De Soto St., Pittsburgh, PA 15213, United States. kan62@pitt.edu
Telephone: +1-412-3833913 Fax: +1-412-6247397
Received: November 4, 2016
Peer-review started: November 6, 2016
First decision: November 30, 2016
Revised: February 17, 2017
Accepted: May 3, 2017
Article in press: May 5, 2017
Published online: June 15, 2017
Processing time: 222 Days and 22.6 Hours
Abstract
AIM

To test associations between statin use and cognitive impairment in adults with childhood-onset type 1 diabetes (T1D).

METHODS

In 2010-13, n = 108 middle-aged participants from ongoing observational Pittsburgh Epidemiology of Diabetes Complications Study underwent neurocognitive assessment (mean age and T1D duration of 49 and 41 years, respectively). All were diagnosed with childhood-onset (i.e., prior to age 18) T1D between 1950 and 1980 and were seen within one year of diagnosis at Children’s Hospital of Pittsburgh. Self-reported statin use (yes/no and if yes, name of statin) was collected biennially from parent study baseline (1986-1988) to time of neurocognitive testing. Logistic regression models tested associations between statin use groups and cognitive impairment (defined as having two or more cognitive test scores 1.5SD or worse than published norms) while linear regression models tested associations between statin use groups and cognitive domain z-scores (domains: Verbal IQ, memory, executive function, psychomotor speed, and visuo-construction). All models controlled for education and age. To address confounding by indication, models were repeated using a propensity score for statin use.

RESULTS

Of the 108 participants, 51 reported never using statins. Median duration of statin use among the 57 ever users was 6 years. These 57 ever statin users were split to create two groups (≤ or > median years of statin use): 1-6 years (n = 25), and 7-12 years (n = 32). Compared with never users, using statins 1-6 years tripled the odds of cognitive impairment (OR = 3.16; 95%CI: 0.93-10.72; P = 0.06) and using statins 7-12 years almost quintupled the odds of cognitive impairment (OR = 4.84; 95%CI: 1.63-14.44; P = 0.005). Compared with never users, using statins 1-6 or 7-12 years was related to worse performance in the memory domain (β = -0.52; P = 0.003, and -0.39; P = 0.014, respectively). Adjusting for coronary artery disease, low density lipoprotein cholesterol, and Apo E4 status did not substantially alter results, and none of these covariates were significantly related to cognitive outcomes (all P > 0.05). Propensity score analyses support that associations between poor cognitive outcomes and statin use were not due merely to confounding by indication.

CONCLUSION

Statin use was associated with cognitive impairment, particularly affecting memory, in these middle-aged adults with childhood-onset T1D, whom at this age, should not yet manifest age-related memory deficits.

Keywords: Type 1 diabetes; Cognitive impairment; Memory; Statin use; Cohort study

Core tip: Animal and cell culture studies show that statins can damage cerebral gray and white matter, thereby affecting cognitive function. Findings from human studies remain controversial; early observational studies reported that statin use negatively affected cognition, especially memory, while more recent studies have not replicated these findings. Even though statins are widely prescribed for people with type 1 diabetes (T1D), only one study to date has examined whether statin use is related to cognitive impairment in this patient population. We propose that deleterious effects statins may exert on cognition may be more pronounced in people with T1D, as these individuals are already at an increased risk of cognitive impairment due to long-term exposure to metabolic dysregulation.