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Summary
This summary is machine-generated.

Cerebrovascular disease (CeVD) biomarkers, including diffusion MRI measures, show earlier progression than white matter hyperintensities (WMH). These findings enable earlier detection and intervention for vascular contributions to cognitive impairment (VCI).

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Area of Science:

  • Neuroimaging
  • Neurology
  • Biomarker Discovery

Background:

  • Cerebrovascular disease (CeVD) is a common co-pathology with Alzheimer's Disease, but its operationalization for estimating vascular contributions to cognitive impairment (VCI) is limited.
  • Novel diffusion MRI markers (FA, FW, PSMD, ARTS) and white matter hyperintensities (WMH) are proposed as surrogates for early and late CeVD changes, respectively.
  • Characterizing the temporal progression of these CeVD biomarkers is crucial for accurate staging and clinical assessment.

Purpose of the Study:

  • To characterize the temporal progression of novel diffusion MRI markers and WMH for enhanced CeVD biomarker staging.
  • To establish reliable cut-points for classifying normal/abnormal CeVD biomarkers in relation to VCI.
  • To investigate the early detection potential of diffusion MRI markers compared to WMH.

Main Methods:

  • Utilized CeVD biomarker data from 3,953 Mayo Clinic Study of Aging participants, with an 80-20 training-testing split for cut-point estimation.
  • Classified participants into VCI+ and VCI- groups using Fazekas scale and Clinical Dementia Rating (CDR) criteria.
  • Employed nonlinear mixed-effects (NLME) models on longitudinal data from 2,047 participants to analyze temporal biomarker progression, accounting for covariates and random effects.

Main Results:

  • Diffusion MRI biomarkers (FW, PSMD, ARTS) demonstrated consistent progression approximately 10 years earlier than WMH.
  • Whole-brain diffusion MRI measures showed high correlation with WMH, indicating synchronized progression with a time offset.
  • The regional genu measure (interhemispheric disconnection) exhibited earlier and steadier progression with lower correlation to WMH.

Conclusions:

  • Established cut-points for diffusion MRI markers using VCI classification, with the 'accuracy young referent' criterion outperforming others.
  • Diffusion MRI markers' earlier progression highlights their potential for early detection of CeVD and VCI.
  • These findings support improved clinical assessment and targeted interventions for CeVD by leveraging advanced neuroimaging techniques.