Distinguishing Early from Late Mild Cognitive Impairment Using Magnetic Resonance Free-Water Diffusion Tensor Imaging

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease. Differentiating early MCI (EMCI) from late MCI (LMCI) is crucial for early diagnosis and intervention. This study used free-water diffusion tensor imaging (fw-DTI) to investigate white matter differences and voxel-based correlations with Mini-Mental State Examination (MMSE) scores. Data from the Alzheimer's Disease Neuroimaging Initiative included 476 healthy controls (CN), 137 EMCI participants, and 62 LMCI participants. Significant MMSE differences were found between the CN and MCI groups, but not between EMCI and LMCI. However, distinct white matter changes were observed: LMCI showed a higher f-index and lower fw-fractional anisotropy (fw-FA) compared to EMCI in several white matter regions. These findings indicate specific white matter tracts involved in MCI progression. Voxel-based correlations between fw-DTI metrics and MMSE scores further supported these results. In conclusion, this study provides crucial insights into white matter changes associated with EMCI and LMCI, offering significant implications for future research and clinical practice.