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Cited by 366Dementia and Cognitive Impairment ResearchCancer-related cognitive impairment studiesAlzheimer's disease research and treatments

The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease

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Rosenberg, Paul B., Mielke, Michelle M., Appleby, Brian S., Oh, Esther S., Geda, Yonas E., Lyketsos, Constantine G.·2013·The American Journal of Geriatric Psychiatry
DOI 10.1016/j.jagp.2013.01.006PMC PMC3428504
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Abstract

Objectives Individuals with mild cognitive impairment (MCI) are at high risk of developing dementia and/or Alzheimer disease (AD). Among persons with MCI, depression and anxiety have been associated with an increased risk of incident dementia. We examined whether neuropsychiatric symptoms in MCI increased the risk of incident dementia (all-cause) and incident AD. Design Longitudinal cohort study followed annually (median: 1.58 years). Setting National Alzheimer's Coordinating Center database combining clinical data from 29 Alzheimer's Disease Centers. Participants A total of 1,821 participants with MCI. Measurements 1) Progression to dementia (all-cause) or AD, 2) Neuropsychiatric Inventory Questionnaire (NPI-Q), 3) Geriatric Depression Scale (GDS), 4) Clinical Dementia Rating Global Score and Sum of Boxes, and 5) Mini-Mental State Examination (MMSE). The association of covariates with risk of incident dementia or AD was evaluated with hazard ratios (HR) determined by Cox proportional-hazards models adjusted for age, ethnicity, Clinical Dementia Rating Global Score and Sum of Boxes, and MMSE. Results A total of 527 participants (28.9%) progressed to dementia and 454 (24.9%) to AD. Baseline GDS > 0 was associated with an increased risk of incident dementia (HR: 1.47, 95% CI: 1.17-1.84) and AD (HR: 1.45, 95% CI: 1.14-1.83). Baseline NPI > 0 was associated with an increased risk of incident dementia (HR: 1.37, 95% CI: 1.12-1.66) and AD (HR: 1.35, 95% CI: 1.09-1.66). Conclusions Neuropsychiatric symptoms in MCI are associated with significantly an increased risk of incident dementia and AD. Neuropsychiatric symptoms may be among the earliest symptoms of preclinical stages of AD and targeting them therapeutically might delay transition to dementia.

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  • During the extended preclinical period prior to dementia diagnosis, many patients develop behavioral or neuropsychiatric changes, including agitation, irritability, decreased motivation, loss of empathy, and depression, which increase the risk of transition to mild cognitive impairment and AD.

    “During this extended preclinical period prior to the dementia diagnosis, many patients develop behavioral or neuropsychiatric changes, including agitation, irritability, decreased motivation, loss of empathy, and depression, which increase the risk of transition to mild cognitive impairment and AD.12-14”

    From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [13]

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  • These behavioral changes are associated with increased risk of dementia and AD, suggesting that they contribute to AD pathogenesis.

    “These behavioral changes are associated with increased risk of dementia and AD,13,14 suggesting that they contribute to AD pathogenesis.13,14”

    From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [13]

    The Results and Discussion report that neuropsychiatric symptoms in people with MCI are associated with increased risk of dementia and AD. But the Discussion says the authors cannot infer, without biomarkers or autopsy data, that those symptoms reflect the AD neuropathological process. The paper therefore does not establish that the behavioral changes contribute to AD pathogenesis. (LLM, conf=0.90)

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  • These behavioral changes may be the earliest symptoms of preclinical stages of AD.

    “Thus, these behavioral changes may be the earliest symptoms of preclinical stages of AD.13,14”

    From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [13]

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Research works printed but not linked: 33

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Authors
Rosenberg, P. B., Mielke, M. M., Appleby, B. S., Oh, E. S., Geda, Y. E., & Lyketsos, C. G.
Affiliations
  • Johns Hopkins University (US)
  • Mayo Clinic (US)
ORCID
Venue
The American Journal of Geriatric Psychiatry
Publisher
Elsevier BV
Published
2013-07
Volume
21
Issue
7
Pages
685-695
ISSN
1064-7481 (ISSN-L)
DOI
10.1016/j.jagp.2013.01.006
PMC
PMC3428504
OpenAlex
W2088391242
Cited by
366
References
9
Citations by year
2026: 18 · 2025: 30 · 2024: 41 · 2023: 31 · 2022: 36 · 2021: 29 · 2020: 46 · 2019: 24 · 2018: 21 · 2017: 27 · 2016: 15 · 2015: 20 · 2014: 15 · 2013: 10
FWCI
14.22
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Geriatric Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (K08AG029157, U01AG016976, R01AG039384, AG029157-01A1)
  • National Institute of Mental Health (U01MH066136)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
mild cognitive impairment, neuropsychiatric symptoms, incident dementia, Alzheimer's disease, depression, anxiety, Geriatric Depression Scale, Neuropsychiatric Inventory Questionnaire, dementia risk, preclinical Alzheimer's disease
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Anxiety, Dementia, Depression, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Cohort Studies, Proportional Hazards Models, Disease Progression, Cognitive Dysfunction

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