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000257341 1001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b0$$eFirst author$$udzne
000257341 245__ $$aMRI-based basal forebrain atrophy and volumetric signatures associated with limbic TDP-43 compared to Alzheimer's disease pathology.
000257341 260__ $$a[Amsterdam]$$bElsevier$$c2023
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000257341 520__ $$aIt is not clear to which degree limbic TDP-43 pathology associates with a cholinergic deficit in the absence of Alzheimer's disease (AD) pathology.Replicate and extend recent evidence on cholinergic basal forebrain atrophy in limbic TDP-43 and evaluate MRI based patterns of atrophy as a surrogate marker for TDP-43.We studied ante-mortem MRI data of 11 autopsy cases with limbic TDP-43 pathology, 47 cases with AD pathology, and 26 mixed AD/TDP-43 cases from the ADNI autopsy sample, and 17 TDP-43, 170 AD, and 58 mixed AD/TDP-43 cases from the NACC autopsy sample. Group differences in basal forebrain and other brain volumes of interest were assessed using Bayesian ANCOVA. We assessed the diagnostic utility of MRI based patterns of brain atrophy using voxel-based receiver operating characteristics and random forest analyses.In the NACC sample, we found moderate evidence for the absence of a difference in basal forebrain volumes between AD, TDP-43, and mixed pathologies (Bayes factor(BF)10 = 0.324), and very strong evidence for lower hippocampus volume in TDP-43 and mixed cases compared with AD cases (BF10 = 156.1). The ratio of temporal to hippocampus volume reached an AUC of 75% for separating pure TDP-43 from pure AD cases. Random-forest analysis between TDP-43, AD, and mixed pathology reached only a multiclass AUC of 0.63 based on hippocampus, middle-inferior temporal gyrus, and amygdala volumes. Findings in the ADNI sample were consistent with these results.A comparable degree of basal forebrain atrophy in pure TDP-43 cases compared to AD cases encourages studies on the effect of cholinergic treatment in amnestic dementia due to TDP-43. A distinct pattern of temporo-limbic brain atrophy may serve as a surrogate marker to enrich samples in clinical trials for the presence of TDP-43 pathology.
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000257341 650_2 $$2MeSH$$aHumans
000257341 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000257341 650_2 $$2MeSH$$aBayes Theorem
000257341 650_2 $$2MeSH$$aBasal Forebrain: diagnostic imaging
000257341 650_2 $$2MeSH$$aBasal Forebrain: pathology
000257341 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000257341 650_2 $$2MeSH$$aAtrophy: pathology
000257341 650_2 $$2MeSH$$aDNA-Binding Proteins: metabolism
000257341 650_2 $$2MeSH$$aCholinergic Agents
000257341 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000257341 650_7 $$2Other$$aAD pathology
000257341 650_7 $$2Other$$aAutopsy
000257341 650_7 $$2Other$$aCholinergic deficit
000257341 650_7 $$2Other$$aImaging signature
000257341 650_7 $$2Other$$aLimbic TDP-43
000257341 650_7 $$2Other$$aMRI
000257341 650_7 $$2NLM Chemicals$$aCholinergic Agents
000257341 7001_ $$0P:(DE-HGF)0$$aGrothe, Michel J$$b1
000257341 7001_ $$aInitiative, Alzheimer's Disease Neuroimaging$$b2$$eCollaboration Author
000257341 773__ $$0PERI:(DE-600)1471408-5$$a10.1016/j.nbd.2023.106070$$gVol. 180, p. 106070 -$$p106070$$tNeurobiology of disease$$v180$$x0969-9961$$y2023
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