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@ARTICLE{Teipel:257341,
      author       = {Teipel, Stefan and Grothe, Michel J},
      collaboration = {Initiative, Alzheimer's Disease Neuroimaging},
      title        = {{MRI}-based basal forebrain atrophy and volumetric
                      signatures associated with limbic {TDP}-43 compared to
                      {A}lzheimer's disease pathology.},
      journal      = {Neurobiology of disease},
      volume       = {180},
      issn         = {0969-9961},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2023-00410},
      pages        = {106070},
      year         = {2023},
      note         = {CC BY-NC-ND},
      abstract     = {It 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.},
      keywords     = {Humans / Alzheimer Disease: pathology / Bayes Theorem /
                      Basal Forebrain: diagnostic imaging / Basal Forebrain:
                      pathology / Magnetic Resonance Imaging / Atrophy: pathology
                      / DNA-Binding Proteins: metabolism / Cholinergic Agents /
                      DNA-Binding Proteins (NLM Chemicals) / AD pathology (Other)
                      / Autopsy (Other) / Cholinergic deficit (Other) / Imaging
                      signature (Other) / Limbic TDP-43 (Other) / MRI (Other) /
                      Cholinergic Agents (NLM Chemicals)},
      cin          = {AG Teipel},
      ddc          = {570},
      cid          = {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:36898615},
      doi          = {10.1016/j.nbd.2023.106070},
      url          = {https://pub.dzne.de/record/257341},
}