Medication self-administration (MSA) and awareness of MSA: life-relevant markers of cognitive impairment

Project summary/abstract It is well-understood that life-relevant changes in independence occur as early warnings of lost cognitive resilience, and eventually Alzheimer's Disease and related dementias (ADRD). We and others demonstrated that medication self-administration (MSA) provides exactly the opportunity needed for early identification of ADRD. However, several knowledge gaps hinder routine assessment of this critical health self-management skill in current care. We lack studies directly comparing self-reported measures and objective, convenient MSA assessments in the general population. In addition, the impact of CVD and cognitive risk factors on MSA errors and MSA overestimation, strong predictors of memory performance and daily life functional independence, is unclear. To address these challenges, we propose to perform an objective MSA assessment in the Framingham Heart Study. This cohort has well-characterized cognitive assessment for up to three decades. An estimated 1185 surviving participants from the second-generation and Omni 1 Framingham Heart Study cohorts are expected to participate as part of their 11th /6th comprehensive health examination, starting September 2025. Our central hypothesis is that MSA errors and self- overestimation are early indicators of disabling brain and behavior changes. In Aim 1, we will cross-sectionally associate MSA errors and MSA self-overestimation, using the Hopkins Medication Schedule and a visual vertical scale, with behavioral- (neuropsychological performance) and brain-based ADRD biomarkers (atrophy, white matter change). In Aim 2, we will associate MSA assessment with a trajectory of cognitive decline on the Mini-Mental State (MMSE) and neuropsychological testing, as occurs in ADRD. In Aim 3, we will establish whether MSA assessment predicts greater care needs and life-relevant disability, examining the Allocation of Caregiver Time Survey, ER visits and hospitalizations, physical activities, and physical performance. MSA assessment is brief and feasible, with potentially greater public health value value than standard generic cognitive screening. We expect that our study will establish a role for objective MSA assessment in geriatric and cognitive care, and we also expect our research results to improve the MSA assessment standard used in pharmaceutical trials that enroll the aged.