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Record W4412785839 · doi:10.1002/dad2.70151

Apathy and affective symptoms associated with elevated plasma neurofilament light but not p‐tau181 in Alzheimer's disease

2025· article· en· W4412785839 on OpenAlexfundno aff
Matthew Kang, Dhamidhu Eratne, Samantha M. Loi, Christa Dang, Alexander Santillo, Henrik Zetterberg, Kaj Blennow, Philip B. Mitchell, Malcolm Hopwood, Charles B. Malpas, Dennis Velakoulis

Bibliographic record

VenueAlzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierPfizerNovartis Pharmaceuticals CorporationBiogenEli Lilly and CompanyBristol-Myers SquibbBioClinicaMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeEisaiAlzheimer's AssociationNational Health and Medical Research CouncilFoundation for the National Institutes of Health
KeywordsApathyDiseaseMedicineInternal medicineNeurofilamentAlzheimer's diseasePsychologyClinical psychologyPsychiatryImmunohistochemistry

Abstract

fetched live from OpenAlex

INTRODUCTION: Apathy and affective neuropsychiatric symptoms (NPS) are prevalent in Alzheimer's disease (AD), yet their neurobiological cause is still unclear. We examined associations between plasma neurofilament light chain (NfL) and tau pathology (p-tau181) with apathy and affective symptoms in mild cognitive impairment (MCI) and AD dementia. METHODS: This longitudinal study analyzed data from 781 participants with MCI and AD dementia enrolled in ADNI, with annual blood samples collected over 4 years. NPS were assessed via the Neuropsychiatric Interview (NPI), and biomarker trajectories were analyzed using mixed-effects models. RESULTS: Elevated plasma NfL levels were associated with apathy, anxiety and depression in MCI and AD dementia, with apathy linked to a significantly higher rate of NfL increase, indicating accelerated neurodegeneration. DISCUSSION: Apathy and affective symptoms may indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression. Highlights: Apathy and affective neuropsychiatric symptoms (NPS) are highly prevalent in clinical Alzheimer's disease (AD).The presence of apathy, depression or anxiety was associated with higher plasma levels of neurofilament light chain (NfL).Apathy was associated with an accelerated increase in plasma NfL levels over time.Apathy and affective NPS were not associated with p-tau181 levels in plasma.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.315
Teacher spread0.297 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations2
Published2025
Admission routes1
Has abstractyes

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