Diffusion kurtosis imaging detects cortical microstructural alterations in amyloid-positive MCI patients.

Background: Alzheimer's disease (AD) is characterized by early accumulation of amyloid-β (Aβ) plaques and tau pathology which precede overt neurodegeneration and cognitive decline. Detecting microstructural brain changes associated with Aβ deposition before the onset of atrophy is critical for early diagnosis and intervention. Objective: This study investigates whether diffusion kurtosis imaging (DKI) can detect early microstructural alterations in cortical and subcortical gray matter (GM) associated with Aβ pathology in individuals with mild cognitive impairment (MCI). Methods: Using DKI-derived metrics-mean kurtosis (MK) and mean diffusivity (MD) - we assessed cortical and subcortical microstructure in 67 participants (23 cognitively normal [CN], 44 MCI, including 29 Aβ-positive). Aβ burden was quantified using Results: Aβ-positive MCI patients exhibited significantly elevated cortical MK, particularly in the left lateral temporal lobe and right precuneus, compared to both CN and Aβ-negative MCI groups. MK positively correlated with Aβ burden in parietal and temporal cortices, even in the absence of cortical atrophy. In contrast, MD showed weaker and less consistent associations with Aβ and was more strongly influenced by age. No significant subcortical MK or MD differences were observed. Conclusion: Elevated MK in Aβ-positive MCI patients suggests that DKI can detect early microstructural changes associated with the presence of amyloid pathology before the onset of cortical atrophy. MK may serve as a promising non-invasive biomarker for identifying prodromal AD and monitoring disease progression.