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Regional cingulum disruption, not gray matter atrophy, detects cognitive changes in amnestic mild cognitive impairment subtypes.

Amnestic mild cognitive impairment (aMCI), which has a high risk of progression to Alzheimer's disease (AD), can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. We investigated the integrity of regional gray matter and segments of the cingulum bundle with diffusion spectrum imaging tract-specific analysis, and their relationships to neuropsychological functioning, in 46 individuals with aMCI (S-aMCI n = 24; M-aMCI n = 22) and 36 healthy controls (HC). Results demonstrated that although both aMCI groups were impaired on all memory measures relative to HCs, the M-aMCI group demonstrated worse performance on paired association memory and on selective executive function relative to the S-aMCI group. The two aMCI groups did not show significant atrophy in regional gray matter indices as compared to the HC group, but the M-aMCI group showed significant disruption in white matter of the left anterior and inferior cingulum bundles relative to the S-aMCI and HC groups. Furthermore, disruption in the inferior cingulum bundles was significantly associated with executive function and attention/processing speed in all aMCI participants above and beyond the contribution of bilateral hippocampal volumes. Overall, these results indicate that the degeneration of cingulum fibers did not appear to arise from degeneration of the corresponding cerebral cortex. It also suggests relatively greater sensitivity of a white matter biomarker and comprehensive neuropsychological evaluation over gray matter biomarkers in early detection of AD.