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000276279 1001_ $$0P:(DE-2719)9002248$$aSchumacher, Julia$$b0$$eFirst author$$udzne
000276279 245__ $$aAssociation of Alzheimer's and Lewy body disease pathology with basal forebrain volume and cognitive impairment.
000276279 260__ $$aLondon$$bBioMed Central$$c2025
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000276279 520__ $$aDegeneration 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.
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000276279 650_2 $$2MeSH$$aHumans
000276279 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000276279 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000276279 650_2 $$2MeSH$$aLewy Body Disease: pathology
000276279 650_2 $$2MeSH$$aLewy Body Disease: diagnostic imaging
000276279 650_2 $$2MeSH$$aFemale
000276279 650_2 $$2MeSH$$aMale
000276279 650_2 $$2MeSH$$aCognitive Dysfunction: pathology
000276279 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000276279 650_2 $$2MeSH$$aAged
000276279 650_2 $$2MeSH$$aBasal Forebrain: pathology
000276279 650_2 $$2MeSH$$aBasal Forebrain: diagnostic imaging
000276279 650_2 $$2MeSH$$aAged, 80 and over
000276279 650_2 $$2MeSH$$aAtrophy: pathology
000276279 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000276279 650_2 $$2MeSH$$aHippocampus: pathology
000276279 650_2 $$2MeSH$$aHippocampus: diagnostic imaging
000276279 650_2 $$2MeSH$$aOrgan Size
000276279 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b1$$udzne
000276279 7001_ $$0P:(DE-2719)9000306$$aStorch, Alexander$$b2$$eLast author$$udzne
000276279 773__ $$0PERI:(DE-600)2506521-X$$a10.1186/s13195-025-01678-x$$gVol. 17, no. 1, p. 28$$n1$$p28$$tAlzheimer's research & therapy$$v17$$x1758-9193$$y2025
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