ArticleResearch square2026
Cholinergic Basal Forebrain Atrophy Accelerates Cognitive Decline via Cortical Thinning: The Moderating Role of Amyloid-β Pathology in Preclinical Alzheimer's Disease.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Degeneration of the cholinergic basal forebrain (cBF) is a hallmark of early neurodegeneration in Alzheimer's disease (AD). While cBF atrophy has been linked to cognitive decline, the extent to which cortical thinning mediates this association, particularly in preclinical AD, remains unclear. Furthermore, the influence of amyloid-β (Aβ) pathology on these relationships warrants further investigation. This study analyzed longitudinal MRI and PIB-PET data from 230 cognitively normal older adults in the Harvard Aging Brain Study, with a mean follow-up of six years. FreeSurfer was used to quantify cBF volume and cortical thickness, while cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite-5 (PACC5). Linear mixed-effects models evaluated longitudinal associations between cBF atrophy, cortical thinning, and cognitive decline. Mediation analyses assessed whether cortical thinning mediated the relationship between cBF degeneration and cognitive decline, and the moderating effect of Aβ burden was examined. Progressive cortical thinning in multiple cognition-related regions was significantly associated with longitudinal cBF atrophy. Mediation analysis revealed that cortical thinning accounted for approximately 44% of the association between cBF degeneration and cognitive decline. These effects were more pronounced in Aβ-positive individuals, suggesting a synergistic interaction between amyloid pathology and cholinergic degeneration. These findings indicate that cBF atrophy accelerates cognitive decline by driving cortical thinning, with Aβ pathology further exacerbating these effects. This study enhances understanding of the structural mechanisms underlying cognitive decline in preclinical AD and highlights potential early intervention targets.
Identifiers
What OpenQuestion holds
Registered trials
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.