Parallel changes in cognition, neuropsychiatric symptoms, and amyloid in cognitively unimpaired older adults and those with mild cognitive impairment.

Introduction: Alzheimer's disease (AD) diagnosis centers on cognitive impairment despite other early indicators like neuropsychiatric symptoms (NPSs) and amyloid beta (Aβ) accumulation. This study examined how cognition, NPS, and Aβ changes are interrelated over time in individuals without dementia.

Methods: Participants were 1247 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 and -3 cohorts with at least 48 months of follow-up. Cognitive domains were assessed via ADNI composite measures, NPS via the neuropsychiatric inventory, and Aβ via standardized uptake value ratio (SUVR) composite scores. Co-occurring changes were evaluated with parallel process models.

Results: NPS was longitudinally associated with performance in each cognitive domain. Negative baseline Aβ-cognition associations were observed in three cognitive domains. No Aβ-NPS associations were observed.

Discussion: This study demonstrated strong longitudinal relationships between NPS and cognition in preclinical and prodromal stages of AD. Future studies should incorporate NPS into models of disease trajectories to improve early detection and prediction of disease progression.

Highlights: Co-occurring changes in Aβ, cognition, and neuropsychiatric symptoms are understudied. We found relationships between neuropsychiatric symptoms and cognition. We found baseline, but not longitudinal, Aβ and cognition associations. Changes in neuropsychiatric symptoms should be included in early detection models of ADRD.