Distinct brain atrophy patterns in Lewy body disease: The impact and interaction of comorbid neuropathologies revealed by voxel-based morphometry

BackgroundIt has become evident that various different neuropathologies including Alzheimer's disease neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC), and argyrophilic grain disease (AGD) coexist in patients with Lewy body disease (LBD). However, the effect of these comorbidities on brain atrophy remains understudied.ObjectiveThis study aimed to explore the morphological impacts of comorbidities using voxel-based morphometry (VBM).MethodsThirty-four individuals with a neuropathological diagnosis of LBD were included. Antemortem whole-brain 3D-T1-weighted images were preprocessed using Computational Anatomy Toolbox 12. Associations between gray matter (GM) atrophy and specific comorbid neuropathology, as well as interactions among them, were analyzed using VBM.ResultsNeurofibrillary tangle (NFT) pathology exhibited inverse correlations with GM volumes of the right temporal, bilateral frontal lobes, and left posterior cingulate gyrus. Neuritic plaque (NP) pathology-related GM atrophy was localized to the left posterior cingulate gyrus and parts of the parietal lobes. LATE-NC exhibited inverse correlations mainly in the left temporal lobe and left-dominant limbic lobes including the hippocampi. AGD pathology-related GM atrophy was predominant in the left-dominant limbic lobes and left temporal pole. Small vessel disease (SVD) scores were inversely correlated with GM volumes in the left frontal lobe and bilateral cerebellar hemispheres. Interactions between NFT and LATE-NC were limited to limbic and temporal lobes, while interactions between NFT and NP, SVD and NFT or LATE-NC showed more posterior-dominant distributions.ConclusionsVBM analyses revealed distinct atrophy patterns reflective of isolated neuropathologies. Furthermore, the study suggests that interactions between neuropathologies may influence brain atrophy patterns.