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

Abstract

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.

Figure 1

Participant enrolment and exclusion details. MCI, mild cognitive impairment.

Figure 2

Kaplan–Meier curves on the risk of progression to severe dementia, focusing only on the individual NPSs that had been identified to be significant in the current study. For AD, this is based on the presence of seven significant NPSs (namely, depression, anxiety, apathy, delusions, hallucinations, irritability and motor disturbance). For non-AD, this is based on the presence of two significant NPSs (namely, delusions and hallucinations).

Figure 3

A directed acyclic graph to explain the apparent association between NPSs in early dementia and progression to severe dementia.