White matter microstructure and motor function in amnestic mild cognitive impairment and Alzheimer's dementia

Introduction Up to 30% of amnestic mild cognitive impairment (aMCI) subjects exhibit motor dysfunction. However, the relationship between white matter microstructural connectivity (SC) and motor function across the Alzheimer's disease (AD) spectrum remains unclear. This study investigated 1) white matter microstructural differences among cognitively unimpaired (CU) individuals, those with aMCI, and those with mild AD; and 2) associations between white matter microstructure and motor performance. Methods Participants (CU = 68, aMCI = 44, AD = 34) underwent diffusion- and T1-weighted MRI. Whole-brain SC was assessed using weighted streamline count from probabilistic tractography between regions of the Brainnetome atlas. A subset (n = 103) also completed motor assessments (finger tapping, grip strength, spiral tracing, sequence learning). Group differences and AFD–motor associations were evaluated using threshold-free network-based statistics, corrected for multiple comparisons. Results Compared with CU participants, those with AD exhibited reduced SC in 268 connections, predominantly involving the temporal lobe, thalamus, and hippocampus. Compared with aMCI, AD participants showed reduced SC in three connections linking frontal, parietal, and temporal regions. No significant SC differences were observed between CU and aMCI, and SC was not associated with motor performance. Conclusion White matter SC is affected in AD, particularly in medial temporal lobe regions that are known to be affected early in the disease. Absence of differences between CU and aMCI, and small differences between aMCI and AD suggests that SC changes appear later in the disease course. The lack of SC-motor associations could reflect lack of variation in motor behavior in the sample.