The differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition and mild cognitive impairment

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Abstract

Background: Mild cognitive impairment (MCI) has been related to impairment in cerebrovascular perfusion and microstructural magnetic resonance imaging (MRI) parameters. However, the relationship between cerebrovascular perfusion and microstructure remains understudied, especially within normal-appearing white matter (NAWM). Objective: This study aimed to investigate the differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition (NC) and MCI using multiple MRI measurements within NAWM. Methods: We examined differences between 24 MCI and 55 NC participants in NAWM for cerebrovascular perfusion and microstructural measures, including cerebrovascular reactivity (CVR), cerebral blood flow, arterial transit time (ATT), and intracellular volume fraction (ICVF), isotropic volume fraction, and orientation dispersion index in models adjusted for vascular risk factors including hypertension, glycemic status, and the presence of APOE ε4 allele. Results: In the voxel-wise analyses within NAWM, participants with MCI exhibited lower CVR, prolonged ATT, and lower ICVF. Additionally, ATT and ICVF demonstrated a negative interrelationship in voxel clusters affected by MCI. Conclusions: Impaired ATT and ICVF in NAWM appeared to be closely interlinked in MCI, while CVR served as an independent imaging biomarker. Further investigation into the intrinsic link between ATT and ICVF in NAWM is warranted.

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Kim, D., Yoon, S., Hughes, T. M., Wu, Y. C., Harvey, D., Lipford, M. E., … Jung, Y. (2025). The differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition and mild cognitive impairment. Journal of Alzheimer’s Disease, 108, S293–S305. https://doi.org/10.1177/13872877251360740

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