Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer's disease dementia

Objectives: To examine trajectories of depression and apathy over a 5-year follow-up period in (prodromal) Alzheimer's disease (AD), and to relate these trajectories to AD biomarkers. Methods: The trajectories of depression and apathy (measured with the Neuropsychiatric Inventory or its questionnaire) were separately modeled using growth mixture models for two cohorts (National Alzheimer's Coordinating Center, NACC, n = 22 760 and Alzheimer's Disease Neuroimaging Initiative, ADNI, n = 1 733). The trajectories in ADNI were associated with baseline CSF AD biomarkers (Aβ_42, t-tau, and p-tau) using bias-corrected multinomial logistic regression. Results: Multiple classes were identified, with the largest classes having no symptoms over time. Lower Aβ₄₂ and higher tau (ie, more AD pathology) was associated with increased probability of depression and apathy over time, compared to classes without symptoms. Lower Aβ₄₂ (but not tau) was associated with a steep increase of apathy, whereas higher tau (but not Aβ₄₂) was associated with a steep decrease of apathy. Discussion: The trajectories of depression and apathy in individuals on the AD spectrum are associated with AD biomarkers.