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Dementia is strongly associated with atrophy of medial temporal lobe structures even after accounting for neuropathologies
Author(s) -
Woodworth Davis C.,
SheikhBahaei Nasim,
Scambray Kiana Alexis,
Phelan Michael,
Corrada Maria M.M.,
Kawas Claudia H.,
Sajjadi S. Ahmad
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046160
Subject(s) - dementia , atrophy , neuropathology , hippocampal sclerosis , dementia with lewy bodies , pathology , white matter , psychology , temporal lobe , medicine , alzheimer's disease , voxel based morphometry , neuroscience , magnetic resonance imaging , disease , radiology , epilepsy
Background Brain atrophy is associated with various neuropathologies as well as clinical status of dementia. However, few studies have examined if dementia has an independent effect on brain atrophy. In this study, we examined the pattern of atrophy associated with dementia while accounting for the most common dementia‐related neuropathologies. Method We used data from the National Alzheimer’s Coordinating Center (NACC) (09/2005‐03/2017) and identified 129 participants with suitable 3D‐T1w MRI and autopsy data. We determined dementia status at visit closest to MRI. We used the following dichotomized neuropathological variables in our analysis: Alzheimer’s disease neuropathology, hippocampal sclerosis, Lewy Bodies, cerebral amyloid angiopathy, atherosclerosis, gross infarcts, microinfarcts, and micro/macro hemorrhages. We used the Computational Anatomy Toolbox (CAT12) to segment the T1w scans into tissue types and generate gray matter density maps. First, we performed a voxel‐based morphometry (VBM) analysis to identify regions associated with dementia. We further explored this relationship by analyzing the volumes of the identified regions of interest (ROI). Also, to examine the association of dementia with global measures of atrophy, we assessed the relation of dementia with total gray matter, white matter, and cerebrospinal fluid. We used multiple linear regression models of density/volumes in relation to dementia while adjusting for neuropathologies, sex, age, education, years from MRI to death, and intracranial volume. Result Table‐1 summarizes participant characteristics. VBM showed that grey matter atrophy of hippocampus and surrounding structures had the strongest association with dementia (Figure‐1). Therefore, we selected the hippocampus, amygdala, and medial temporal cortex for ROI analysis. We found strong associations with dementia for volumes of the hippocampus, amygdala, and medial temporal cortex (P<0.0001 and semi‐partial correlations≥0.25 for each, Table‐2). Dementia status accounted for more variance in atrophy in these structures (∼8%) compared with all demographic and neuropathological variables; the only exception was hippocampal sclerosis which accounted for more variance in hippocampal atrophy (10%, Table‐3). Conclusion Even after accounting for the most common neuropathologies, dementia still had the strongest association with atrophy of medial temporal lobe structures. This suggests that atrophy of the hippocampus and medial temporal lobe is most related to clinical dementia as opposed to Alzheimer's disease neuropathology.