Structural Gray and White Matter Correlates of Awareness in Alzheimer’s Disease

Abstract

Background: Unawareness of disease is a common feature of Alzheimer’s disease (AD), but few studies explored its neural correlates. Additionally, neural correlates according to the object of awareness are unexplored. Objective: To investigate structural brain correlates in relation to different objects of awareness. Methods: 27 people with AD underwent MRI scanning on a 3T Siemens Prisma. T1-MPRAGE was used to investigate cortical thickness and white matter microstructure was defined by DTI as fractional anisotropy, mean, axial, and radial diffusivity. Preprocessing used FreeSurfer6.0, ExploreDTI, and FSL-TBSS. Awareness of disease, cognitive deficits, emotional state, relationships, and functional capacity were assessed with the short version of the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia. Voxel-wise correlations between brain structure and awareness were determined by FSL-PALM. Analyses were corrected for multiple comparisons using Threshold Free Cluster Enhancement and FWE. Results: Lower left hemisphere cortical thickness was related to poorer disease awareness uncorrected and corrected for age, sex, and MMSE. In the uncorrected model, mainly right-sided, but also left temporal lower cortical thickness was related to decreased awareness of cognitive deficits. Correcting for age, sex, and MMSE eliminated correlations for the right hemisphere, but extensive correlations in the left hemisphere remained. For white matter integrity, higher right hemisphere MD was related to lower cognitive awareness deficits, and lower FA was related to lower functional capacity awareness. Conclusion: Findings suggest that extensive regions of the brain are linked to self-awareness, with particular frontal and temporal alterations leading to unawareness, in agreement with theoretical models indicating executive and mnemonic forms of anosognosia in AD.