Evidence map›Paper›PMID 40731233›Full record

ArticleThe journal of prevention of Alzheimer's disease2025

Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer's disease.

Si Cen, Lijuan Wang, Meiling Qiu, Zhongqiang Xu, Li Xu, Rui Bao, Xiaolei Tang, Juanyu Gong, Jinting Wu, Zhiding Shao and 4 more

Abstract read
In one paragraph

Article in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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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

14 authors.

Si CenThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Lijuan WangThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Meiling QiuThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Zhongqiang XuThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Li XuThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Rui BaoThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Radiology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Xiaolei TangThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Translational Medicine Center, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Juanyu GongThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Jinting WuThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Zhiding ShaoThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Tonghua ZhangThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Radiology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China. Electronic address: zth7607@163.com.
Fan YangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: yangfan42001@163.com.
Wencai DingThe Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China; Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China. Electronic address: dingneurology@wnmc.edu.cn.
Harvard Aging Brain Study (HABS)

Funding

Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Hyun-Sik Yang · 2010 to 2026
$50.2M
NIA NIH HHS P01 AG036694
6 · The paper itself

Abstract

backgroundCholinergic basal forebrain (cBF) atrophy is a critical early marker of neurodegeneration in Alzheimer's disease (AD). While cBF degeneration is linked to cognitive decline, the role of cortical thinning in this process, especially during the preclinical phase of AD, remains underexplored. Additionally, the impact of amyloid-β (Aβ) pathology on these relationships warrants further examination.

methodsWe analyzed longitudinal structural MRI and PIB-PET data from 230 cognitively normal older adults enrolled in the Harvard Aging Brain Study, with a mean follow-up of six years. cBF volume and cortical thickness were quantified using FreeSurfer. Cognitive performance was assessed with the Preclinical Alzheimer Cognitive Composite-5 (PACC5). Linear mixed-effects models were used to investigate the longitudinal associations between cBF atrophy, cortical thinning, and cognitive decline. Mediation analyses explored whether cortical thinning mediated the relationship between cBF degeneration and cognitive decline, and the moderating role of Aβ burden was examined.

resultsProgressive cortical thinning in multiple cognition-related regions was significantly associated with cBF atrophy. Mediation analysis revealed that cortical thinning accounted for approximately 44 % of the relationship between cBF degeneration and cognitive decline. These associations were more pronounced in individuals with elevated Aβ, suggesting a synergistic interaction between amyloid pathology and cholinergic system degeneration.

conclusionsOur findings suggest that cBF atrophy accelerates cognitive decline through its impact on cortical thinning, with Aβ pathology further exacerbating these effects. These results highlight the potential of cBF and cortical thinning as early biomarkers for preclinical AD and underscore the importance of targeting cholinergic dysfunction in early intervention strategies.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBasal ForebrainCerebral Cortical ThinningCognitive DysfunctionAgedAged, 80 and overAtrophyCholinergic NeuronsFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMalePositron-Emission TomographyAmyloid beta-PeptidesAmyloid-β PathologyCholinergic basal forebrainCognitive declineCortical thinningPreclinical Alzheimer’s Disease

Identifiers

PMID40731233
PMCPMC12627883

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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.