Evidence map›Paper›PMID 40851415›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Late-life emergence of neuropsychiatric symptoms and risk of cognitive impairment in cognitively unimpaired individuals.

Therese H Kim, Elizabeth Head, Craig E L Stark, Lorena Sordo, Katharine A Kirby, Maria G Corona, Michelle McDonnell, Joshua D Grill, David L Sultzer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Neuropsychiatric symptoms preceding cognitive impairment: diagnostic value and clinical relevance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  6. Emergent neuropsychiatric symptoms as preclinical flags of cognitive decline: Clinical implications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  7. Article
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Therese H KimInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.ORCID 0009-0003-1146-6746
Elizabeth HeadInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.
Craig E L StarkInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.
Lorena SordoInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.
Katharine A KirbyCenter for Statistical Consulting, Department of Statistics, University of California, Irvine, Irvine, California, USA.
Maria G CoronaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.
Michelle McDonnellInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.
Joshua D GrillInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.
David L SultzerInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.ORCID 0009-0006-5264-5611

Funding

The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Mathew Mark Blurton-Jones · 2020 to 2026
$27.9M
NIA NIH HHSNIH HHS P30AG066519Roche Diagnostics
6 · The paper itself

Abstract

introductionNeuropsychiatric symptoms (NPS) often precede cognitive impairment. We investigated the longitudinal relationship between emergent, significant NPS and cognitive decline in cognitively unimpaired older adults. We also assessed the combined effect of NPS and Alzheimer's disease (AD) biomarkers on subsequent cognitive impairment.

methodsWe included 190 cognitively unimpaired participants without NPS at baseline and tracked the emergence of significant NPS and conversion to mild cognitive impairment (MCI).

resultsThe average follow-up was 8.1 years, with a maximum of 19 years. Participants with emergent, significant NPS had a 3.92-fold higher risk of cognitive impairment than those without (95% confidence interval 1.51-10.17, P = 0.005). Individuals with NPS and AD biomarkers showed a markedly higher conversion rate to MCI than those with neither risk factor. DISCUSSION: Our findings emphasize the role of emergent, significant NPS as early clinical indicators of cognitive impairment and suggest the potential benefit of incorporating clinical symptoms and neurobiological markers to better predict cognitive course. HIGHLIGHTS: We investigated the association between emergent neuropsychiatric symptoms (NPS) and conversion to mild cognitive impairment (MCI). One hundred ninety cognitively unimpaired individuals were followed for an average of 8.1 years. Emergent NPS increased the risk of conversion to MCI > 3-fold. After emergent NPS, cognitive test performance declined. The co-occurrence of NPS and high cerebrospinal fluid phosphorylated tau181 amplified the risk of MCI.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedAged, 80 and overBiomarkersDisease ProgressionFemaleHumansLongitudinal StudiesMaleNeuropsychological TestsRisk Factorstau ProteinsBiomarkerstau ProteinsAlzheimer's diseasecerebrospinal fluid biomarkersGeriatric Depression Scalelongitudinal cohort studymild behavioral impairmentMild Behavioral Impairment Checklistmild cognitive impairmentNeuropsychiatric Inventoryphosphorylated tau181

Identifiers

PMID40851415
PMCPMC12375875

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.