Associations between white matter integrity of the cingulum bundle, surrounding gray matter regions, and cognition across the dementia continuum

IntroductionPrevious Alzheimer's disease and related dementias (AD/ADRD) research studies have illustrated the significance of studying alterations in white matter (WM). Fewer studies have examined how WM integrity, measured with diffusion tensor imaging (DTI), is associated with volume of gray matter (GM) regions and measures of cognitive function in aged participants spanning the dementia continuum.MethodsMagnetic resonance imaging and cognitive data were collected from 241 Boston University Alzheimer's Disease Research Center participants who spanned from cognitively normal controls to amnestic mild cognitive impairment to having dementia. Primary DTI tracts of interest were the cingulum ventral (CV) and cingulum dorsal (CD) pathways. GM regions of interest (ROIs) were in the medial temporal lobe (MTL), prefrontal cortex, and retrosplenial cortex. Analyses of covariance models were used to assess differences in WM integrity across groups (control, amnestic mild cognitive impairment, and dementia). Multiple linear regression models were used to assess associations between WM integrity and GM volume, and with measures of memory and executive function.ResultsDifferences in WM integrity were shown in both cingulum pathways in participants across the dementia continuum. Associations between WM integrity of both cingulum pathways and volume of selected GM ROIs were widespread. Functionally significant associations were found between WM of the CV pathway and memory, independent of MTL GM volume.DiscussionDifferences in WM integrity of the cingulum bundle and surrounding GM ROI are likely related to the progression of AD/ADRD. Such differences should continue to be studied, particularly in association with memory performance. Key Findings: Differences exist in the white matter integrity of the cingulum bundle between participants who are on the dementia continuum.White matter integrity of the cingulum is associated with gray matter volume.White matter integrity of the cingulum ventral, independent of gray matter volume, may be predictive of memory performance.dagger image