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.