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Lookup NU author(s): Emeritus Professor David Brooks
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2026 Nielsen, Parbo, Ismail, B. Dalby, Tietze, Brændgaard, Gottrup, Brooks, Østergaard and Eskildsen.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 11C-PiB PET imaging. Cortical atrophy, hippocampal volume, and white matter hyperintensities (WMH) were also evaluated. 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.
Author(s): Nielsen RB, Parbo P, Ismail R, B Dalby R, Tietze A, Braendgaard H, Gottrup H, Brooks DJ, Ostergaard L, Eskildsen SF
Publication type: Article
Publication status: Published
Journal: Frontiers in Dementia
Year: 2026
Volume: 4
Online publication date: 06/01/2026
Acceptance date: 02/12/2025
Date deposited: 02/02/2026
ISSN (electronic): 2813-3919
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/frdem.2025.1725754
DOI: 10.3389/frdem.2025.1725754
Data Access Statement: The raw data supporting the conclusions of this article is available here: https://doi.org/10.6084/m9.figshare.30850301.
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