Original Investigation
Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults

https://doi.org/10.1016/j.jacc.2021.04.075Get rights and content
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Abstract

Background

The neurocognitive effect of statins in older adults remain uncertain.

Objectives

The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.

Methods

This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer’s disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer’s disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified.

Results

Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02).

Conclusions

In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials.

Key Words

aged
cognitive function
dementia
hydroxymethylglutaryl CoA reductase inhibitors
statins

Abbreviations and Acronyms

3MS
Modified Mini-Mental State Examination
AD
Alzheimer’s disease
CI
confidence interval
CVD
cardiovascular disease
HR
hazard ratio
LDL-C
low-density lipoprotein cholesterol
MCI
mild cognitive impairment

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