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Observational Study
. 2021 Jun 29;77(25):3145-3156.
doi: 10.1016/j.jacc.2021.04.075.

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

Zhen Zhou  1 , Joanne Ryan  2 , Michael E Ernst  3 , Sophia Zoungas  2 , Andrew M Tonkin  2 , Robyn L Woods  2 , John J McNeil  2 , Christopher M Reid  4 , Andrea J Curtis  2 , Rory Wolfe  2 , Jo Wrigglesworth  2 , Raj C Shah  5 , Elsdon Storey  2 , Anne Murray  6 , Suzanne G Orchard  2 , Mark R Nelson  7 ; ASPREE Investigator Group
Affiliations
Observational Study

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

Zhen Zhou et al. J Am Coll Cardiol. .

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.

Keywords: aged; cognitive function; dementia; hydroxymethylglutaryl CoA reductase inhibitors; statins.

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Conflict of interest statement

Funding Support and Author Disclosures The ASPREE trial was supported by a grant (U01AG029824) from the National Institute on Aging and the National Cancer Institute at the National Institutes of Health, by grants (334047 and 1127060) from the National Health and Medical Research Council of Australia, and by Monash University and the Victorian Cancer Agency. Dr. Tonkin has received research support or honoraria from Merck, Pfizer, and Amgen; has received support from Bayer for materials in the ASPREE trial; and has received National Health and Medical Research Council (NHMRC) grant support for the STAREE trial. Dr. Zoungas has received NHMRC and Australian Heart Foundation research funding as the principal investigator of the STAREE trial; and has received payment to the institution (Monash University) from Eli Lilly Australia, Boehringer-Ingelheim, Merck Sharp & Dohme Australia, AstraZeneca, Novo Nordisk, Sanofi, and Servier for consultancy work outside the submitted work. Dr. Nelson has received honoraria from Sanofi and Amgen; has received support from Bayer for materials in ASPREE; and has received NHMRC grant support for STAREE. Dr. Reid is funded through a NHMRC Principal Research Fellowship. Dr. Shah serves as a noncompensated member of the board of directors of the Alzheimer’s Association, Illinois Chapter; receives research support to his institution, Rush University Medical Center, for his role as a site principal investigator or site subinvestigator for industry-initiated clinical trials and research studies of AD sponsored by Amylyx Pharmaceuticals, Eli Lilly, Genentech, Lundbeck, Merck, Navidea Biopharmaceuticals, Novartis Pharmaceuticals, Roche Holdings, and Takeda Development Center Americas; and is a member of the steering committee of the PREVENTABLE clinical trial. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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