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@ARTICLE{Schumacher:276279,
author = {Schumacher, Julia and Teipel, Stefan and Storch, Alexander},
title = {{A}ssociation of {A}lzheimer's and {L}ewy body disease
pathology with basal forebrain volume and cognitive
impairment.},
journal = {Alzheimer's research $\&$ therapy},
volume = {17},
number = {1},
issn = {1758-9193},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2025-00258},
pages = {28},
year = {2025},
abstract = {Degeneration of the basal forebrain cholinergic system is a
hallmark feature shared by Alzheimer's disease (AD) and Lewy
body disease (LBD) whereas hippocampus atrophy is more
specifically related to AD. We aimed to investigate the
relationship between basal forebrain and hippocampus
atrophy, cognitive decline, and neuropathology in a large
autopsy sample.Data were obtained from the National
Alzheimer's Coordinating Center (NACC). Basal forebrain and
hippocampus volumes were extracted using an established
automated MRI volumetry approach. Associations of regional
volumes with pathological markers (Braak stage, CERAD score,
and McKeith criteria for LB pathology) and cognitive
performance were assessed using Bayesian statistical
methods.We included people with autopsy-confirmed pure AD (N
= 248), pure LBD (N = 22), and mixed AD/LBD (N = 185).
Posterior basal forebrain atrophy was most severe in mixed
AD/LB pathology compared to pure AD (Bayes factor against
the null hypothesis BF10 = 16.2) or pure LBD (BF10 = 4.5).
In contrast, hippocampal atrophy was primarily associated
with AD pathology, independent of LB pathology (pure AD vs.
pure LBD: BF10 = 166, pure AD vs. mixed AD/LBD: BF10 = 0.11,
pure LBD vs. mixed AD/LBD: BF10 = 350). Cognitive
performance was more impaired in AD pathology groups, with
Braak stage being the strongest predictor. Hippocampal
volume partially mediated this relationship between tau
pathology and cognitive impairment, while basal forebrain
volume had a limited role in mediating the relationship
between pathological burden and cognitive outcomes.In a
heterogeneous autopsy sample, AD and LB pathology both
contribute to cholinergic basal forebrain degeneration
whereas hippocampus atrophy is more specifically related to
AD pathology. Cognitive deficits are primarily associated
with tau pathology which is partly mediated by hippocampus,
but not basal forebrain atrophy.},
keywords = {Humans / Alzheimer Disease: pathology / Alzheimer Disease:
diagnostic imaging / Lewy Body Disease: pathology / Lewy
Body Disease: diagnostic imaging / Female / Male / Cognitive
Dysfunction: pathology / Cognitive Dysfunction: diagnostic
imaging / Aged / Basal Forebrain: pathology / Basal
Forebrain: diagnostic imaging / Aged, 80 and over / Atrophy:
pathology / Magnetic Resonance Imaging / Hippocampus:
pathology / Hippocampus: diagnostic imaging / Organ Size},
cin = {AG Storch / AG Teipel},
ddc = {610},
cid = {I:(DE-2719)5000014 / I:(DE-2719)1510100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39865328},
doi = {10.1186/s13195-025-01678-x},
url = {https://pub.dzne.de/record/276279},
}