Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations

ABSTRACT Objective To investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid- β positive individuals across the Alzheimer’s disease (AD) clinical spectrum. Methods We included 1,524 amyloid- β positive individuals from the Amsterdam Dementia Cohort with subjective cognitive decline (SCD, n=113), mild cognitive impairment (MCI, n=321), or dementia (n=1,090). We measured NPS with the neuropsychiatric inventory (NPI), examining total scores and the presence of specific NPI-items. Cognition was assessed across five cognitive domains and with the MMSE. We examined trajectories including model based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time-points (subsample n=520, Mean=1.8 [SD=0.7] years follow-up). Results NPS were prevalent across all clinical AD stages (NPI total score ≥1 81.4% in SCD, 81.2% in MCI, 88.7% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range β :-0.18–0.11, FDR-adjusted p 0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage ( β :-0.13–0.44, FDR-adjusted p >0.05). Conclusion NPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.