Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

ARTICLE HIGHLIGHTS

Research background

Alzheimer’s disease (AD) is a neurodegenerative disease with severe cognitive dysfunction. The prominent clinical manifestations are memory loss, confusion of thinking and logic, and abnormal mental behavior. At present, it is also inclined to think that AD is a chronic inflammatory disease mediated by abnormal autoimmune function. Mononuclear RNA sequencing and transcriptomics analysis show that the abnormal changes in microglia in the brain of AD patients induce a series of abnormal immune function. The activation of abnormal inflammasome represented by nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor protein 3 (NLRP3) inflammasome mediates the secretion of many immune inflammatory factors and subsequent cascades of chronic cascades reactions in immune inflammation. The amyloid β (Aβ) peptide produced by abnormal neurons precipitates and aggregates outside the cell. The hyperphosphorylation of tau protein can also easily cause aggregation, leading to neuron and nerve synaptic dysfunction and cell death, especially small glial cells. Reactive proliferation of glial cells often causes secondary cytopathological reactions in diseased brain regions.

Research motivation

The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important. The ratio of NLR in blood is an important systemic inflammatory biomarker. NLR is calculated by absolute counting of neutrophils divided by absolute counts of lymphocytes. NLR has been reported to be increased in diabetes, hypertension, myocardial infarction. stroke and some tumor patients, which may be a new index to evaluate the prognosis of these patients. The detection of T lymphocytes, B lymphocytes and natural killer cells in blood by flow cytometry can evaluate whether the immune function of AD patients is abnormal. Combined with the detection of relevant biochemical markers and EEG wave indexes by cranial magnetic spectroscopy (MRS), it has great clinical significance for the early diagnosis and prognosis evaluation of AD patients. As far as we know, little research work has been carried out in this regard.

Research objectives

To explore the correlation between abnormal immune function and adverse prognostic factors in AD patients, and hope to find some valuable clues.

Research methods

A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020. Collect cognitive dysfunction performance characteristics, laboratory test data and neuroimaging data from medical records within 24 h of admission, including MMSE score, drawing clock test, blood T lymphocyte subsets, and NLR, disturbance of consciousness, extrapyramidal symptoms, electroencephalogram (EEG) and head nucleus MRS and other data. Multivariate logistic regression analysis was used to determine independent prognostic factors. the modified Rankin scale (mRS) was used to determine whether the prognosis was good. The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.

Research results

Univariate analysis showed that abnormal cellular immune function, extrapyramidal symptoms, obvious disturbance of consciousness, abnormal EEG, increased NLR, abnormal MRS, and complicated pneumonia were related to the poor prognosis of AD patients. Multivariate logistic regression analysis showed that the decrease in the proportion of T lymphocytes in the blood after abnormal cellular immune function (odd ratio: 2.078, 95% confidence interval: 1.156-3.986, P < 0.05) was an independent risk factor for predicting the poor prognosis of AD. The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score (r = 0.578, P < 0.05).

Research conclusions

The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD. It is suggested that the proportion of T lymphocytes less than 55% should be used as the cut-off threshold for predicting the poor prognosis of AD. In addition, MRS combined with EEG detection is also worthy of recognition in predicting the poor prognosis of AD. Yet the early and continuous drug treatment that improve cognitive function is associated with a good prognosis.

Research perspectives

It is speculated that the decline of cellular immune function is not only closely related to the onset of AD, but also has a greater relationship with the poor prognosis of AD. There is increasing evidence that the occurrence of AD is closely related to slow immune inflammation, and the changes of lymphocytes in the blood may be directly related to this slow immune inflammation. In a word, this research still has some valuable findings in predicting the correlation between abnormal cellular immune function and poor prognosis in AD patients.