Polypharmacy and risk of dementia progression in older adults with mild cognitive impairment: A longitudinal cohort study

INTRODUCTION Polypharmacy is common in older adults with mild cognitive impairment (MCI), but its impact on cognitive decline is unclear. Studies on the association between polypharmacy and cognitive outcomes have yielded inconsistent evidence. The objective of this study was to assess the association between polypharmacy and the risk of progression from MCI to dementia. METHODS We conducted a longitudinal cohort study of 237 older adults with MCI in Taiwan. Polypharmacy was defined as the concurrent use of ≥5 prescription medications. Cognitive function was assessed annually using the Clinical Dementia Rating scale. Cox proportional hazards regression models were used to evaluate the association between polypharmacy and dementia risk, adjusting for demographic and clinical covariates. Subgroup analyses examined the effects of different medication counts and specific medications on dementia progression. RESULTS Among 237 participants, 108 (45.6%) had polypharmacy, and 89 were diagnosed with dementia during a median follow‐up of 34 months (interquartile range: 16.7 to 52.6 months). Kaplan–Meier analysis showed a higher dementia‐free survival probability in the polypharmacy group ( p = 0.005). Cox regression analysis revealed that polypharmacy was significantly associated with a reduced risk of MCI progression to dementia (hazard ratio [HR] = 0.49, 95% confidence interval [CI]: 0.31 to 0.78) after adjusting for covariates. Medication counts ranging from ≥5 to ≥8 were significantly associated with a reduced dementia risk, without a clear cut‐off. Further analysis suggested that antihypertensive and lipid‐modifying drugs were associated with a reduced risk of dementia progression. CONCLUSION Our findings suggest that polypharmacy is associated with a lower risk of progression to dementia in people with MCI, highlighting the importance of medication appropriateness over medication count. Future research should optimize pharmacological strategies to balance the risks and benefits of polypharmacy in older adults with MCI. Highlights Polypharmacy was linked to reduced dementia risk in older adults with MCI. No clear medication threshold (≥5 to ≥8) for dementia risk reduction was found. Specific medications were associated with a lower risk of dementia progression. The importance of medication purpose and type over medication count is highlighted. Future studies should optimize pharmacological strategies in older adults with MCI.