MRI-based basal forebrain atrophy and volumetric signatures associated with limbic TDP-43 compared to Alzheimer's disease pathology.

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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)

CONCLUSION

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.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest ST participated in scientific advisory boards of Roche Pharma AG, Biogen, Grifols, and MSD, and is member of the Independent Data Safety and Monitoring Board of the study ENVISION (Biogen). MG reports no conflicts of interest.