BEST FELLOW PAPER: Assessing the Impact of Overactive Bladder Medications on Cognition

Objectives: To evaluate the association of overactive bladder medications on cognitive function among individuals with prospective longitudinal cognitive assessments.

Methods: We evaluated a population-based cohort of cognitive aging individuals 50 years and older, who had serial cognitive assessments from October 2004 through December 2021. Those with dementia at baseline were excluded. Periodic validated cognitive assessments were performed in accordance with the Mayo Clinic Study of Aging protocol at roughly 15-month intervals. Anticholinergic overactive bladder medications were grouped by traditional anticholinergic medications and anticholinergic medications with potentially less CNS exposure (i.e. trospium, fesoterodine, or darifenacin), and compared to no anticholinergic overactive bladder medication exposure (control group). We fit linear mixed effects models with time-dependent exposures to assess the association between overactive bladder anticholinergic medication exposure and subsequent trajectories of cognitive z-scores. Models were adjusted for known factors associated with cognitive decline including sociodemographic features, clinical comorbidities, and genetic factors (apolipoprotein e4 allele status).

Results: We included 5872 participants with a median follow-up of 6.4 years (IQR 3.2, 9.2), including a median of 6 cognitive assessment visits (IQR 3, 8). Amongst study subjects, 443 were exposed to traditional anticholinergic medications, 60 to ‘CNS sparing’ medications, and 5369 had no exposure at baseline or during available follow-up. On multivariable analyses, exposure to any anticholinergic overactive bladder medication was significantly associated with deterioration in longitudinal cognitive scores in the language (p=0.01) and attention assessments (p=0.007) compared to the control cohort. There was no statistically significant change in the rate of deterioration in memory (p= 0.11) or visuospatial (p=0.19) assessments, as well as global z-score (p=0.06). In subgroup analysis, ‘traditional anticholinergic’ medication exposure was associated with worse attention (p=0.01) scores than non-exposed participants. There was no significant association with change in memory (p= 0.35), language (p=0.3), or visual (p=0.58) assessments, or global score (p=0.12). Exposure to ‘CNS sparing’ anticholinergic medications was associated with a deterioration in the language (p=0.006) assessments than controls, but not in assessments of memory (p=0.06), attention (p=0.08), visuospatial (p=0.08) or global z-score (p=0.08). Among female participants, traditional anticholinergic medication exposure was associated with worse global (p=0.02) and visuospatial (p=0.03) scores than non-exposed participants, but this association was not identified for CNS sparing anticholinergic medications (global: p=0.15, visuospatial: p=0.95).

Conclusions: In adults, exposure to anticholinergic overactive bladder medications was associated with worse cognitive scoring in the language and attention domains when compared to non-exposed participants. Among female participants exposure to traditional anticholinergic medication was associated with adverse rate of global cognitive decline and visuospatial scores, whereas exposure to an anticholinergic OAB medication with potentially less CNS exposure was not. Further study of anticholinergic medication subtypes is needed to guide patient counseling and treatment selection.