DOI: 10.1002/dad2.70379 ISSN: 2352-8729

Polypharmacy is associated with lower progression from MCI to Alzheimer's disease, with sex‐specific patterns across drug classes

Mar García‐Zamora, Juan Pardo, Miriam Esteve, Alejandro Martinez‐Gracia, Consuelo Cháfer‐Pericás, Antonio Falcó

Abstract

INTRODUCTION

Polypharmacy is often considered harmful in older adults, yet several cardiovascular and psychiatric drugs target modifiable dementia risk factors. We examined the association between polypharmacy and progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), overall and by sex.

METHODS

In a retrospective cohort of 4557 adults ≥ 50 years with MCI, followed for a mean of 68.7 months, polypharmacy was defined as ≥ 5 medications. Cox models adjusted for age and sex estimated hazard ratios (HRs), including sex‐stratified analyses.

RESULTS

Polypharmacy may be associated with lower likelihood of progression to AD. Sex‐stratified analyses suggested differences: antidiabetics, antithrombotics, sedatives, and antidepressants were mainly associated with lower progression in women; antihypertensives in men; anxiolytics, antipsychotics, and antidementia drugs in both sexes.

DISCUSSION

These observational findings indicate possible associations between medication use and MCI to AD progression, with potential sex‐specific patterns, but causality cannot be inferred. Unmeasured factors and limited covariate adjustment may contribute.

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