Are Drugs that Cause Dysbiosis Longitudinally Associated with Cognitive Scores, Cognitive Impairment, & Dementia?

Abstract Recent research has examined how the microbiome may influence cognitive outcomes; however, there is a paucity of research understanding how medication associated with dysbiosis may be associated with cognitive changes. This study used data from the Health and Retirement Study and the Prescription Drug Study subset for adults 51 and older (n=3,898). Continuous (0-27) and categorical (cognitively normal=12-27; cognitive impairment=7-11; and dementia=0-6) cognitive outcomes were used. Prescriptions utilized were proton pump inhibitors, antibiotics, selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, antihistamines, and a summed dose-response measure. Linear mixed models (LMM) and generalized linear mixed models (GLMM) were used for continuous and binary outcomes. For the LMM model, the main effect for those taking one medication was insignificant; however, the interaction with time showed a significant decrease over time (β: -0.07; 95% confidence interval (CI): -0.14, 0.01). The mean cognitive score was lower for those taking two or more medications (β: -1.48; 95% CI: -2.70, -0.25), although the interaction with time was insignificant. GLMM results showed those taking two or medications had odds that are 612% larger (odds ratio (OR): 7.12; 95% CI: 3.03, 16.71) of going from cognitively healthy to dementia but the interaction with time showed decreased odds over time (OR: 0.92; 95% CI 0.86, 0.97). For cognitive impairment, those who took two or more medications had odds that were 45% larger (OR: 1.45; 95% CI: 1.05, 2.00) of going from cognitively healthy to cognitively impaired. This study indicated a dose-response aspect to taking medications on cognitive outcomes.