Title: Ante-mortem basal forebrain atrophy in pure limbic TAR DNA-binding protein 43 pathology compared with pure Alzheimer pathology Teipel SJ, Grothe MJ Ref: Eur Journal of Neurology, :, 2022 : PubMed
BACKGROUND: Currently, the extent of cholinergic basal forebrain atrophy in relatively pure limbic TAR DNA-binding protein 43 (TDP-43) pathology compared with relatively pure Alzheimer's disease (AD) is unclear. METHODS: We compared ante-mortem MRI based atrophy of the basal forebrain and medial and lateral temporal lobe volumes between 10 autopsy cases with limbic TDP-43 pathology and 33 cases with AD pathology on post-mortem neuropathologic examination from the ADNI cohort. For reference, we studied MRI volumes from cognitively healthy, amyloid PET negative people (n = 145). Group differences were assessed using Bayesian ANCOVA. In addition, we assessed brain-wide regional volume changes using partial least-squares regression (PLSR). RESULTS: We found extreme evidence (Bayes factor (BF)(01) > 600) for a smaller basal forebrain volume in both TDP-43 and AD cases compared with amyloid-negative controls, and moderate evidence (BF(01) = 4.9) that basal forebrain volume was not larger in TDP-43 than in AD cases. The ratio of hippocampus to lateral temporal lobe volumes discriminated between TDP-43 and AD cases with an accuracy of 0.78. PLSR showed higher grey matter in lateral temporal lobes and cingulate and precuneus, and reduced grey matter in precentral and postcentral gyri and hippocampus in TDP-43 compared with AD cases. CONLCUSIONS: Atrophy of the cholinergic basal forebrain appears to be similarly pronounced in cases with limbic TDP-43 pathology as in AD. This suggests that a clinical trial of the efficacy of cholinesterase inhibitors in amyloid-negative cases with amnestic dementia and an imaging signature of TDP-43 pathology may be warranted.
        
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Teipel SJ, Grothe MJ (2022) Ante-mortem basal forebrain atrophy in pure limbic TAR DNA-binding protein 43 pathology compared with pure Alzheimer pathology Eur Journal of Neurology
Teipel SJ, Grothe MJ (2022) Eur Journal of Neurology