Epidemiology of potentially inappropriate medication use and risk for mild cognitive impairment and dementia among ARIC, Look AHEAD, and MESA

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Project Summary/Abstract Use of potentially inappropriate medications (PIMs) among older adults (age ≥65 years) result in preventable adverse health events, including hospitalization and mortality. Certain individual medications that are classified as PIMs are associated with greater risk for dementia, demonstrated to act on the central and peripheral nervous system and block the action of specific neurotransmitters (e.g., anticholinergics block acetylcholine). Registry- based studies show that PIM use increases over older adulthood for individuals with Alzheimer’s disease and related dementias (AD/RD) and matched healthy controls. However, epidemiology of PIM use over older adulthood has not been assessed in multi-ethnic community-based cohorts or in response to a lifestyle intervention. Because PIM use results in avoidable complications, we need to understand epidemiology of PIM use in response to interventions and in relation to subsequent cognitive complications, respectively. Identifying whether lifestyle interventions can reduce PIM use and prevent mild cognitive impairment and dementia would have major clinical and public health implications. This proposal will leverage data from epidemiological studies and a clinical trial to provide estimates of PIM prevalence, incidence, and longitudinal change among three large multi-ethnic and geographically diverse study populations: the Atherosclerosis Risk in Communities (ARIC) Study, Action for Health in Diabetes Study, and Multi-Ethnic Study of Atherosclerosis. This research will estimate (Aim 1) prevalence of PIM use and factors associated with PIM use, (Aim 2) longitudinal change in PIM use during older adulthood and in response to an intensive lifestyle intervention for weight loss, and (Aim 3) the association between PIM use and incident MCI/dementia and brain pathology. This work is significant and innovative because it will provide estimates of PIM use among multi-ethnic cohorts and a new research resource for Look AHEAD and MESA investigators (characterization of PIM use). This proposal will also assess the effect of a lifestyle intervention on longitudinal change in PIM use and will help disentangle the temporal association between PIM use and AD/RD. We have designed each aim to address a critical gap in our understanding of the epidemiology of PIM use, and potential for interventions in older adulthood to reduce AD/RD-related morbidity and mortality due to PIM use. Our team has the research skills, experience, and resources to address these aims in a rigorous and efficient manner. The findings from this work will provide empirical evidence for treatment strategies to reduce PIM use and prevent AD/RD, and to assess whether PIM use is associated with other aging-related conditions.