Hippocampal subfield deformation shows unique patterns associated with amyloid‐beta, TDP‐43, and PHF‐tau burden

Ashley Heywood, Julie A Schneider, David A Bennett, Konstantinos Arfanakis, Faisal Beg, Lei Wang
2020 Alzheimer's & Dementia  
Alzheimer's dementia (AD) is the most common form of dementia in adults over the age of 65, however, current diagnostic tools need to be improved. The relationships between clinical syndromes and pathological causes are complex, which makes accurate diagnosis difficult. The goals are to develop an in vivo hippocampal surface atlas from structural MRI that is predictive of postmortem β-amyloid, paired helical filament (PHF-tau) neurofibrillary tangles (NFTs) and transactive response DNAbinding
more » ... otein-43 (TDP-43) neuropathologies. Method: Using a sample of 101 older adults from two longitudinal cohort studies conducted by the Rush Alzheimer's Disease Center, we utilized hippocampal shape analysis of ante-mortem T1-weighted sMRI to generate surfaces for the whole hippocampus and zones approximating the underlying subfields using a previously developed automated image-segmentation pipeline (Freesurfer-Initiated Large Deformation Diffeomorphic Metric Mapping; FSLDDMM). Multivariate linear regression models were constructed to examine the relationship between shape and pathology measures while accounting for covariates which include co-existing pathologies and other neuropathological variables (hippocampal sclerosis, Lewy bodies, gross infarcts, atherosclerosis, arteriosclerosis, and cerebral amyloid angiopathy). These relationships were mapped onto hippocampal surface locations. In a previous sample of 42 subjects from the same cohort, univariate models were not able to be examined due to low power. Result: A significant and unique pattern of deformation for each neuropathology when accounting for covariates were seen. Specifically, β-amyloid was associated with a significant inward deformation in zones approximating the subiculum, where PHF-tau NFTs were associated with a significant inward deformation along the left hippocampal tail within the subiculum. TDP-43 inclusions were associated with a significant inward deformation in the body of the hippocampus along the CA1/subiculum border. Results were corrected for multiple comparisons using the random field theory (RFT) with a family-wise error rate (FWER) < 0.05. Conclusion: These results indicate a unique pattern of deformation due to individual neuropathology, after accounting for covariates. With the presented increased sample
doi:10.1002/alz.039864 fatcat:kpvcyv6n2jghxcqft3lynhubni