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.
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.
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Who cites it
6 citing papers in PubMed.
- MRI-derived periventricular diffusivity contextualizes plasma pTau217 associations with Alzheimer pathology: a discovery-validation study.Research square · 2026Article
- Long-Term Cognitive and Functional Outcomes of Anesthesia and Surgery in Patients with Dementia.Healthcare (Basel, Switzerland) · 2026Review
- Correspondence of Basal Forebrain Resting-State Functional Connectivity and Cerebral Glucose Metabolism Alterations With Neurotransmitter Maps in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- Neuroprotective Effects of Two N-Benzylamides in Models of Oxidative Stress, Neurite Outgrowth and Neurodegeneration.Oxidative medicine and cellular longevity · 2026Article
- Sleep and stress as modifiable drivers of Alzheimer's disease.NPJ dementia · 2026Review
- Exercise-induced modulation of astrocyte in Alzheimer's disease: mechanisms and therapeutic implications.Frontiers in physiology · 2026Review
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Authors and funding
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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.
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