Supplemental Materials Eikelboom et al. Neuropsychiatric and cognitive symptoms across the Alzheimer's disease clinical spectrum

The objective of this study was 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. In this single-center observational study, we included all individuals who visited the Alzheimer Center Amsterdam and had 1) a clinical diagnosis of subjective cognitive decline (SCD), mild cognitive impairment (MCI), or probable AD dementia, and 2) were amyloid-β positive (A+). We measured NPS with the Neuropsychiatric Inventory (NPI), examining total scores and the presence of specific NPI domains. 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). We included 1,524 amyloid-β positive individuals from the Amsterdam Dementia Cohort with A+ SCD (n=113), A+ MCI (n=321), or A+ AD dementia (n=1,090). NPS were prevalent across all clinical AD stages (≥1 NPS 81.4% in SCD, 81.2% in MCI, 88.7% in dementia; ≥1 clinically relevant NPS 54.0% in SCD, 50.5% in MCI, 66.0% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all AD 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 to 0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI (range β=-0.32 to 0.36, all FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage (range β=-0.13 to 0.44, all FDR-adjusted p>0.05). NPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.