Evidence map›Paper›PMID 42294788›Full record

ArticlePsychological medicine2026

Plasma neurofilament light chain and regional brain atrophy mediate the association of neuropsychiatric symptoms with cognition in Alzheimer's disease: evidence from two population-based studies.

Ya-Yu Wang, Huai-Yuan Zhu, Wei Miao, Zhi-Xin Wang, Jia-Jia Qin, Xiao-Han Song, Yue-Hua Wang, Zhong-Wu Sun, Xia Zhou, Xian-Feng Yu and 2 more

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Article in Psychological medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Ya-Yu WangDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.ORCID https://orcid.org/0009-0004-7736-7991
Huai-Yuan ZhuDepartment of Clinical Pharmacy, The https://ror.org/038hzq450First Affiliated Hospital of Henan Medical University, Weihui, China.
Wei MiaoDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Zhi-Xin WangDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Jia-Jia QinDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Xiao-Han SongDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Yue-Hua WangDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Zhong-Wu SunDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Xia ZhouDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Xian-Feng YuDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Xiao-Qun ZhuDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Alzheimer’s Disease Neuroimaging Initiative

Funding

Major Project of Philosophy and Social Science Research in Colleges and Universities of Jiangsu Province 2022AH040159Science Fund for Distinguished Young Scholars of Anhui Province 2108085MH274
6 · The paper itself

Abstract

backgroundNeuropsychiatric symptoms (NPSs) are prevalent in Alzheimer's disease (AD), yet their neurobiological etiology remains elusive. We investigated relationships between NPS subsyndromes, plasma neurofilament light chain (NFL), AD-vulnerable brain atrophy, and cognition.

methodsWe included 146 participants from a Chinese cohort. NPSs were assessed using the Neuropsychiatric Inventory Questionnaire and clustered into four subsyndromes (hyperactivity, psychosis, affective, apathy), each graded by severity (none, mild, severe). Sequential mediation analyses examined whether NPSs influence cognition through NFL and atrophy. Additionally, 1534 ADNI participants were enrolled to (1) replicate mediation effects; (2) examine longitudinal relationships of NPSs with incident cognitive decline; and (3) evaluate cognitive discrimination of NPSs and NFL and onset hazards of NPS subsyndromes.

resultsIn the discovery cohort, global NPSs burden and three subsyndromes (hyperactivity, affective, apathy) were associated with elevated plasma NFL, poorer global cognition and memory, and reduced brain volumes (all

conclusionsBaseline NPSs were cross-sectionally associated with elevated NFL, brain atrophy, and poorer cognition. Sequential mediation models supported a pathway linking NPSs to cognition via NFL and atrophy, though longitudinal evidence did not fully confirm temporal directionality. These hypothesis-generating findings require prospective validation.

Indexed as

Alzheimer DiseaseBrainCognitive DysfunctionNeurofilament ProteinsAgedAged, 80 and overAtrophyCognitionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleNeuropsychological TestsPsychotic Disordersneurofilament protein LNeurofilament ProteinsAlzheimer’s Diseasebrain structurescognitionneurofilament lightneuropsychiatric symptoms

Identifiers

PMID42294788
PMCPMC13280697

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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.