Neuropsychiatric symptoms in early stage of Alzheimer's and non-Alzheimer's dementia, and the risk of progression to severe dementia

Age Ageing. 2021 Sep 11;50(5):1709-1718. doi: 10.1093/ageing/afab044.


Background: Neuropsychiatric symptoms (NPSs) in early dementia have been suggested to predict a higher risk of dementia progression. However, the literature is not yet clear whether the risk is similar across Alzheimer's dementia (AD) and non-Alzheimer's dementia (non-AD), as well as across different NPSs. This study examined the association between NPSs in early dementia and the risk of progression to severe dementia, specifically in AD and non-AD, as well as across various NPSs.

Method: This cohort study included 7,594 participants who were ≥65 years and had early dementia (global Clinical Dementia Rating [CDR] = 1). Participants completed Neuropsychiatric-Inventory-Questionnaire at baseline and were followed-up almost annually for progression to severe dementia (global CDR = 3) (median follow-up = 3.5 years; interquartile range = 2.1-5.9 years). Cox regression was used to examine progression risk, stratified by AD and non-AD.

Results: The presence of NPSs was associated with risk of progression to severe dementia, but primarily in AD (HR 1.4, 95% confidence interval [CI]: 1.1-1.6) and not in non-AD (HR 0.9, 95% CI: 0.5-1.5). When comparing across various NPSs, seven NPSs in AD were associated with disease progression, and they were depression, anxiety, apathy, delusions, hallucinations, irritability and motor disturbance (HR 1.2-1.6). In contrast, only hallucinations and delusions were associated with disease progression in non-AD (HR 1.7-1.9).

Conclusions: NPSs in early dementia-especially among individuals with AD-can be useful prognostic markers of disease progression. They may inform discussion on advanced care planning and prompt clinical review to incorporate evidence-based interventions that may address disease progression.

Keywords: Alzheimer’s dementia; advanced dementia; behavioural and psychological symptoms of dementia; dementia progression; non-Alzheimer’s dementia; older people.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / epidemiology
  • Apathy*
  • Cohort Studies
  • Dementia* / diagnosis
  • Dementia* / epidemiology
  • Humans
  • Neuropsychological Tests