Association between polypharmacy and cerebral white matter lesions

White matter lesions (WML) are a common finding in the elderly, associated with a range of symptoms and an elevated risk of cerebrovascular events. Despite their prevalence, the underlying pathological mechanisms of WML remain unclear. Similarly, polypharmacy– defined as the concurrent use of six or more drugs– increases with age. This study aimed to examine a potential association between polypharmacy and WML. The research was performed using data from the population-based Heinz Nixdorf Recall 1000Brains study (n=642, 66.6±6.7 years, 55.3% male). WML were identified in nearly all participants (99.7%), while polypharmacy was present in 18.7% of the study population. On average, participants used 3.2 different drugs (standard deviation 2.8), with individual usage ranging from 0 to 17 drugs. The individual WML burden was assessed using the Fazekas score, with a prevalence of 48.6% for participants scoring 0 or 1, 29.4% for those scoring 2, and 22.0% for those scoring 3. Univariate regression analysis showed an association between WML and polypharmacy (odds ratio (OR) 1.54; 95% confidence interval (CI) 1.21–2.30). However, after adjusting for age, hypertension, and stroke in a multivariate model, the ORfor polypharmacy decreased to 1.22 (95% CI 0.79–1.87). In summary, this study demonstrates an association between polypharmacy and WML. However, its cross-sectional design precludes any conclusions about causality. In clinical practice, the high prevalence of WML in elderly patients warrants attention. Polypharmacy poses multiple challenges and may represent an independent risk factor, making de-prescribing a valuable consideration when appropriate. Additionally, polypharmacy could serve as a clinical indicator of potential brain tissue damage in the form of WML.