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

By Willem S Eikelboom, Esther van den Berg, Ellen Singleton, Sara J. Baart, Michiel Coesmans, Annebet E. Leeuwis, Charlotte E. Teunissen, Bart NM van Berckel, Yolande A.L. Pijnenburg, Philip Scheltens, Wiesje M van der Flier, Rik Ossenkoppele, Janne M. Papma

Posted 20 Feb 2021
medRxiv DOI: 10.1101/2021.02.18.21251064

ObjectiveTo investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid-{beta} positive individuals across the Alzheimers disease (AD) clinical spectrum. MethodsWe included 1,524 amyloid-{beta} 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). ResultsNPS were prevalent across all clinical AD stages (NPI total score [&ge;]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 {beta}:-0.18-0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI ({beta}:-0.32- 0.36, FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage ({beta}:-0.13-0.44, FDR-adjusted p>0.05). ConclusionNPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.

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