Evaluating the Repurposing Potential of Statins: Association Between Statin Use and Cognitive Decline in Patients With Mild-to-Moderate Alzheimer’s Disease
Author(s)
Wei Fang Chao, MS, Hsiu-Ting Chien, PhD, Chin-Hsien Lin, PhD, Fang-Ju (Irene) Lin, RPh, PhD.
Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
OBJECTIVES: Statins are hypothesized to have neuroprotective properties and have been proposed as potential repurposing agents for Alzheimer’s disease (AD). This study aimed to evaluate the association between statin initiation and cognitive decline in patients with mild-to-moderate AD.
METHODS: We conducted a retrospective cohort study using electronic health records from a multicenter hospital system. Adults aged ≥65 years with mild-to-moderate AD who initiated cholinesterase inhibitors (CHEIs) between January 2007 and December 2022 were identified. The exposure of interest was the initiation of statin therapy following CHEI treatment. The primary outcome was time to cognitive disease progression, measured by the annualized rate of change in Mini-Mental State Examination (MMSE) or Clinical Dementia Rating (CDR) scores. Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted using Cox proportional hazards models. Baseline confounding was addressed through propensity-score matching (up to 1:4) and alignment on time since CHEI initiation. Covariates included age, sex, low-density lipoprotein cholesterol (LDL-C) levels, baseline MMSE/CDR scores, comorbidities, and concomitant medications.
RESULTS: In the interim analysis, 256 patients who initiated statins post-CHEI were matched to 1,000 non-initiators.. The ITT analysis indicated no statistically significant association between statin initiation and cognitive progression (HR: 1.06; 95% CI: 0.83-1.35). Similar findings were observed in the PP analysis accounting for treatment discontinuation (HR: 1.05; 95% CI: 0.82-1.33). Subgroup and sensitivity analyses are in progress to assess potential effect modifiers and residual confounding.
CONCLUSIONS: Our interim findings do not support a significant association between statin initiation and slowed cognitive decline in patients with mild-to-moderate AD. Future work will explore heterogeneous treatment effects and refine confounding adjustment to better elucidate the repurposing potential of statins in this population.
METHODS: We conducted a retrospective cohort study using electronic health records from a multicenter hospital system. Adults aged ≥65 years with mild-to-moderate AD who initiated cholinesterase inhibitors (CHEIs) between January 2007 and December 2022 were identified. The exposure of interest was the initiation of statin therapy following CHEI treatment. The primary outcome was time to cognitive disease progression, measured by the annualized rate of change in Mini-Mental State Examination (MMSE) or Clinical Dementia Rating (CDR) scores. Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted using Cox proportional hazards models. Baseline confounding was addressed through propensity-score matching (up to 1:4) and alignment on time since CHEI initiation. Covariates included age, sex, low-density lipoprotein cholesterol (LDL-C) levels, baseline MMSE/CDR scores, comorbidities, and concomitant medications.
RESULTS: In the interim analysis, 256 patients who initiated statins post-CHEI were matched to 1,000 non-initiators.. The ITT analysis indicated no statistically significant association between statin initiation and cognitive progression (HR: 1.06; 95% CI: 0.83-1.35). Similar findings were observed in the PP analysis accounting for treatment discontinuation (HR: 1.05; 95% CI: 0.82-1.33). Subgroup and sensitivity analyses are in progress to assess potential effect modifiers and residual confounding.
CONCLUSIONS: Our interim findings do not support a significant association between statin initiation and slowed cognitive decline in patients with mild-to-moderate AD. Future work will explore heterogeneous treatment effects and refine confounding adjustment to better elucidate the repurposing potential of statins in this population.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO110
Topic
Clinical Outcomes, Epidemiology & Public Health
Topic Subcategory
Clinical Outcomes Assessment
Disease
Mental Health (including addition), Neurological Disorders