Baseline cortical amyloid-β levels are associated with subsequent study-partner-rated apathy in community-dwelling older adults

BackgroundApathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) and has been linked to greater levels of AD biomarkers (amyloid-β, tau). However, it is unclear whether early patterns of amyloid deposition may impact development of apathy symptoms in the future.ObjectiveWe sought to examine whether amyloid-β levels, both globally and in brain regions associated with motivation, could predict future apathy symptoms.MethodsParticipants (n = 199, mean age = 79.9) were part of the Harvard Aging Brain Study, a longitudinal observational cohort of individuals without cognitive or psychiatric impairment at baseline. All underwent MRI and Pittsburgh Compound B (PiB)-PET for amyloid-β at baseline and completed questionnaires of self- and study-partner-rated apathy 7.8 ± 1 years later using the Apathy Evaluation Scale. Linear regression models assessed whether regional PiB levels predicted future apathy scores.ResultsHigher baseline cortical PiB levels in a frontal, lateral parieto-temporal, and retrosplenial aggregate were associated with greater study-partner-rated apathy, but not self-rated apathy, and no specific regional associations were observed outside of the aggregate.ConclusionsThese results provide insight into early neurobiological underpinnings of AD-related apathy. Additionally, these data may have clinical implications regarding the risk of developing apathy symptoms in amyloid-β-positive individuals as cognition declines.