Neuropathological features associated with basal forebrain atrophy in Alzheimer’s disease

Objective: To study the neuropathological correlates of cholinergic basal
forebrain atrophy as determined using ante-mortem MRI in the Alzheimer’s
disease (AD) spectrum. Methods: We determined associations between basal
forebrain (BF) volume from antemortem MRI brain scans and post-mortem
assessment of neuropathological features, including neuritic plaques,
neurofibrillary tangles (NFT), Lewy body (LB) pathology, and TDP-43, in 64
cases of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.
For comparison, we assessed neuropathological features associated with
hippocampal and parahippocampal gyrus atrophy. In addition to region of
interest-based analysis, we determined the association of
neuropathological features with whole brain grey matter volume using
regionally unbiased voxel-based volumetry. Results: BF atrophy was
associated with Thal amyloid phases (95% confidence interval -0.49 -
-0.01, p=0.049) and presence of LB pathology (95% CI -0.54 - -0.06,
p=0.015), as well as with the degree of LB pathology within the Nucleus
basalis Meynert (NbM) (95% CI -0.54 - -0.07, p=0.025). These effects were
no more significant after false discovery rate (FDR) correction.
Hippocampal atrophy was significantly associated with the presence of
TDP-43 pathology (95% CI 0.61 - -0.17, p=0.003; surviving FDR correction),
in addition to dentate gyrus NFT load (95% CI -0.49 - 0.01, p = 0.044;
uncorrected). Voxel-based analysis confirmed spatially restricted effects
of Thal phases and presence of LB pathology on BF volume. Conclusions:
These findings indicate that neuropathological correlates of regional
atrophy differ substantially between different brain regions that are
typically involved in AD-related neurodegeneration, including different
susceptibilities to common co-morbid pathologies.