Prescription medications and co‐morbidities in late middle‐age are associated with lower executive function: Results from WRAP

Background Aging is often accompanied by the accumulation of chronic illnesses such as diabetes, cardiovascular disease or hypertension and a corresponding increase in use of medications to manage these conditions. Polypharmacy (use of multiple prescription medications) is a growing health concern and has been associated with poorer clinical outcomes in older adults. This study investigates associations between comorbidities, polypharmacy and longitudinal cognitive performance in an Alzheimer’s disease (AD) risk‐enriched cohort, the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Method Eligible WRAP participants included 1039 (free of dementia or clinical impairment not due to mild cognitive impairment (MCI) and with >=2 visits with cognitive composites, self‐reported health history, and concurrent medication records. Sums of prescribed medications and self‐reported co‐morbidities (include self‐ report over the lifetime) (Table 1) were calculated for each visit and converted to z‐scores for use in mixed effects models of cognition (covariates: age, gender, education, WRAT III reading recognition, practice and study site). Linear mixed effects analyses first examined whether associations between medications, comorbidities and cognitive z‐scores varied across cognitive domains of working memory, immediate recall, delayed recall, executive function, and a preclinical Alzheimer’s cognitive composite (PACC3) before examining associations with each cognitive composite. In secondary analyses, we examined whether number of medications and comorbidities interacted with each other or modified age trajectories. Result Sample characteristics are shown in Table 2 overall and by gender (mean(sd) baseline age=58.99(6.60)). More comorbidities were associated with more prescription medications (Figure 1). More comorbidities and medications were associated with lower executive function (β = ‐0.11, p=.002; β = ‐0.07, p = 0.047; Table 3); using z‐scores of 10 th and 90 th centile with model parameters, those with low co‐morbidities and medications performed an average of 0.39 SD higher than those elevated on both (Figure 2). Conclusion Associations between medications, comorbidities, and executive function suggest that persons with more comorbidities and medications may be either at increased risk of reaching clinical levels of impairment earlier than healthier, less medicated peers, or may have potentially reversible clinical impairment. Researchers should be aware of the possibility that medication use and comorbidity may impact cognitive performance (and by extension, adjudicated cognitive status).