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. 2020 Nov 25;6(1):e12108.
doi: 10.1002/trc2.12108. eCollection 2020.

Statin therapy and risk of Alzheimer's and age-related neurodegenerative diseases

Georgina Torrandell-Haro  1   2 , Gregory L Branigan  1   2   3 , Francesca Vitali  1   4   5 , Nophar Geifman  6 , Julie M Zissimopoulos  7 , Roberta Diaz Brinton  1   2   4
Affiliations

Statin therapy and risk of Alzheimer's and age-related neurodegenerative diseases

Georgina Torrandell-Haro et al. Alzheimers Dement (N Y). .

Abstract

Introduction: Establishing efficacy of and molecular pathways for statins has the potential to impact incidence of Alzheimer's and age-related neurodegenerative diseases (NDD).

Methods: This retrospective cohort study surveyed US-based Humana claims, which includes prescription and patient records from private-payer and Medicare insurance. Claims from 288,515 patients, aged 45 years and older, without prior history of NDD or neurological surgery, were surveyed for a diagnosis of NDD starting 1 year following statin exposure. Patients were required to be enrolled with claims data for at least 6 months prior to first statin prescription and at least 3 years thereafter. Computational system biology analysis was conducted to determine unique target engagement for each statin.

Results: Of the 288,515 participants included in the study, 144,214 patients (mean [standard deviation (SD)] age, 67.22 [3.8] years) exposed to statin therapies, and 144,301 patients (65.97 [3.2] years) were not treated with statins. The mean (SD) follow-up time was 5.1 (2.3) years. Exposure to statins was associated with a lower incidence of Alzheimer's disease (1.10% vs 2.37%; relative risk [RR], 0.4643; 95% confidence interval [CI], 0.44-0.49; P < .001), dementia 3.03% vs 5.39%; RR, 0.56; 95% CI, 0.54-0.58; P < .001), multiple sclerosis (0.08% vs 0.15%; RR, 0.52; 95% CI, 0.41-0.66; P < .001), Parkinson's disease (0.48% vs 0.92%; RR, 0.53; 95% CI, 0.48-0.58; P < .001), and amyotrophic lateral sclerosis (0.02% vs 0.05%; RR, 0.46; 95% CI, 0.30-0.69; P < .001). All NDD incidence for all statins, except for fluvastatin (RR, 0.91; 95% CI, 0.65-1.30; P = 0.71), was reduced with variances in individual risk profiles. Pathway analysis indicated unique and common profiles associated with risk reduction efficacy.

Discussion: Benefits and risks of statins relative to neurological outcomes should be considered when prescribed for at-risk NDD populations. Common statin activated pathways indicate overarching systems required for risk reduction whereas unique targets could advance a precision medicine approach to prevent neurodegenerative diseases.

Keywords: Alzheimer's disease; Parkinson's disease; age; amyotrophic lateral sclerosis; bioinformatics; biology pathway analysis; cholesterol; multiple sclerosis; neurodegenerative diseases; statins.

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Conflict of interest statement

Dr Brinton reported receiving grants from the Women's Alzheimer's Movement and the National Institute on Aging during the conduct of the study. No other disclosures were reported.

Figures

FIGURE 1
FIGURE 1
Study design and patient breakdown. Abbreviation: NDD, neurodegenerative disease
FIGURE 2
FIGURE 2
Relative risk of developing NDDs for patients receiving any statin versus individual statins. A, Risk ratio for each NDD based on exposure to any statin. B, Risk ratio for composite NDD group and every NDD for individual statin therapies. Abbreviations: AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; MS, multiple sclerosis; NDD, neurodegenerative diseases; PD, Parkinson's disease; RR, relative risk
FIGURE 3
FIGURE 3
Hazard ratios for propensity score–matched patients for developing NDD, AD, dementia, PD. Abbreviations: AD, Alzheimer's disease; NDD, neurodegenerative diseases; PD, Parkinson's disease
FIGURE 4
FIGURE 4
Gene ontology biological processes analysis: unique versus common. A, Protein‐protein interactors shown are of the highest confidence (STRING score >800). Extended interactome shown in Figure S1 in supporting information. B, Unique and common gene ontology terms of interest for statin clusters. Extended version in Figure S1
See this image and copyright information in PMC

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