Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer's and non-Alzheimer's dementia

Abstract

Background: Neuropsychiatric symptoms (NPS) have been reported to be useful in predicting incident dementia among cognitively normal older persons. However, the literature has not been conclusive on the differential utilities of the various NPS in predicting the subtypes of dementia. This study compared the risks of Alzheimer's and non-Alzheimer's dementia associated with the various NPS, among cognitively normal older persons. Methods: This cohort study included 12,452 participants from the Alzheimer's Disease Centers across USA, who were ≥ 60 years and had normal cognition at baseline. Participants completed the Neuropsychiatric Inventory-Questionnaire at baseline and were followed up almost annually for incident dementia (median follow-up = 4.7 years). Symptom clusters of NPS - as identified from exploratory and confirmatory factor-analyses - were included in the Cox regression to investigate their associations with incident dementia. Results: The various NPS showed independent yet differential associations with incident dementia. Although psychotic symptoms were rarely endorsed by the participants, they predicted much higher risk of dementia (HR 3.6, 95% CI 2.0-6.4) than affective symptoms (HR 1.5, 95% CI 1.2-1.8) or agitation symptoms (HR 1.6, 95% CI 1.3-2.1). Psychotic symptoms predicted all dementia subtypes, while affective and agitation symptoms differentially predicted some subtypes. Across dementia subtypes, psychotic symptoms had relatively higher risk estimates than affective or agitation symptoms, with the risk estimates being particularly high in non-Alzheimer's dementia. Conclusions: Among cognitively normal individuals, the presence of NPS may warrant greater clinical vigilance as precursors to dementia and its subtypes. The findings highlight the need for further research to enrich our understanding on the neurobiological links between various NPS and dementia subtypes. They may also change the clinical approach in managing late-life psychotic symptoms, requiring a greater emphasis on dementia surveillance in the diagnostic criteria of late-life psychotic disorders.