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

Liew, Tau Ming

doi:10.1093/ageing/afab044

Cited by 38Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

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

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Liew, Tau Ming·2021·Age and Ageing

DOI 10.1093/ageing/afab044PMC PMC8437074

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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.

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The most common symptoms of AD are short-term memory loss, followed by progressive impairment in implicit and explicit memory, and neuropsychiatric symptoms with eventual loss of ability to perform basic daily duties.
“The most common symptoms of AD are short-term memory loss, which is followed by a progressive impairment in both implicit and explicit memory. Those who have the condition also exhibit neuropsychiatric symptoms, and with time, they lose their ability to perform basic daily duties [24,25,26,27,28].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [24]
AD is categorized into three stages: mild, moderate, and severe.
“AD is categorized into three stages: mild, moderate, and severe [24,25,26,27,28].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [24]

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Additional file 2 of The reporting of neuropsychiatric symptoms in electronic health records of individuals with Alzheimer’s disease: a natural language processing study
Eikelboom, W. S., Singleton, E. H., van den Berg, E., de Boer, C., Coesmans, M., Goudzwaard, J. A., Vijverberg, E. G. B., Pan, M., Gouw, C., Mol, M. O., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26589027
Additional file 1 of The reporting of neuropsychiatric symptoms in electronic health records of individuals with Alzheimer’s disease: a natural language processing study
Eikelboom, W. S., Singleton, E. H., van den Berg, E., de Boer, C., Coesmans, M., Goudzwaard, J. A., Vijverberg, E. G. B., Pan, M., Gouw, C., Mol, M. O., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26589024
Additional file 1 of Systemic and central nervous system neuroinflammatory signatures of neuropsychiatric symptoms and related cognitive decline in older people
Clark, C., Richiardi, J., Maréchal, B., Bowman, G. L., Dayon, L., & Popp, J. (2022) · Figshare · doi:10.6084/m9.figshare.19921025
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Liew, T. M., Yip, K. F., Narasimhalu, K., Ting, S. K. S., Li, W., Tay, S. Y., & Koay, W. I. (2026) · medRxiv · doi:10.64898/2026.01.16.26344274
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The Progression of Neuropsychiatric Symptoms in Alzheimer’s Disease During a Five-Year Follow-Up: Kuopio ALSOVA Study
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Authors: Liew, T. M.
Affiliations: National University of Singapore (SG)
Corresponding author: Liew, Tau Ming
ORCID: Liew, Tau Ming
Venue: Age and Ageing
Publisher: Oxford University Press (OUP)
Published: 2021-03-25
Volume: 50
Issue: 5
Pages: 1709-1718
ISSN: 0002-0729 (ISSN-L)
1468-2834
DOI: 10.1093/ageing/afab044
PMC: PMC8437074
OpenAlex: W3136920246
Cited by: 38
References: 59
Citations by year: 2026: 4 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 1
FWCI: 4.66
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Age and Ageing (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: NIH (U01 AG016976)
National Medical Research Council (NMRC/CSSSP/0014/2017, NMRC/Fellowship/0030/2016)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords: neuropsychiatric symptoms, Alzheimer's disease, non-Alzheimer's dementia, dementia progression, early-stage dementia, prognostic factors, depression, anxiety, apathy, delusions, hallucinations, irritability, motor disturbances, Clinical Dementia Rating, advance care planning
MeSH terms: Alzheimer Disease, Dementia, Humans, Neuropsychological Tests, Cohort Studies, Apathy

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

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