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

TL;DR

Diffusion kurtosis imaging reveals early brain changes in people with mild cognitive impairment who have amyloid buildup, potentially aiding early Alzheimer's detection.

Contribution

This study shows that mean kurtosis from DKI can detect cortical microstructural changes linked to amyloid pathology before atrophy occurs.

Findings

Aβ-positive MCI patients had higher cortical mean kurtosis in specific brain regions compared to controls and Aβ-negative MCI.

Mean kurtosis correlated with Aβ burden in parietal and temporal cortices, even without cortical atrophy.

Mean diffusivity showed weaker and less consistent associations with Aβ compared to mean kurtosis.

Abstract

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.

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).

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 11C-PiB PET imaging. Cortical atrophy, hippocampal volume, and white matter hyperintensities (WMH) were also evaluated.

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.

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.

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