Biological validation of peak‐width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium

Nov 21, 2024Alzheimer's & dementia : the journal of the Alzheimer's Association

Biological confirmation of peak-width of skeletonized mean diffusivity as a marker for vascular cognitive impairment and dementia

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Abstract

Higher was associated with lower general cognition (Beta -0.8, P < 0.001).

PSMD, a marker derived from neuroimaging, reflects cerebral small vessel disease.
The relationship between PSMD and cognitive function was observed in a sample of 396 participants and replicated in three additional cohorts.
The findings indicate that PSMD may provide insights into cognitive impairment independent of other factors like age and education.
PSMD accounted for cognitive status beyond the influence of .

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BACKGROUND: (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure of general cognitive function using linear regression models adjusting for confounders.

RESULTS: Higher PSMD was associated with lower general cognition in MarkVCID-1 independent of age, sex, education, and intracranial volume (Beta [95% confidence interval], -0.8 [-1.2, -0.4], P < 0.001). These findings were replicated in independent samples. Furthermore, PSMD explained cognitive status above and beyond .

DISCUSSION: Our biological validation work supports the pursuit of larger clinical validation studies evaluating PSMD as a susceptibility/risk biomarker of small vessel disease contributing to cognitive impairment and dementia.

HIGHLIGHTS: Peak-width of skeletonized mean diffusivity (PSMD) is a novel small vessel disease neuroimaging biomarker. A prior instrumental validation study demonstrated that PSMD is a robust biomarker. This biological validation study shows that high PSMD relates to worse cognition. PSMD explains cognitive function above and beyond white matter hyperintensities. Future clinical validation will assess PSMD as a vascular contribution to cognitive impairment and dementia biomarker in clinical trials.

Key numbers

-0.8

Decrease in Cognitive Function

Beta coefficient from MarkVCID-1 cohort analysis.

396

Participants in MarkVCID-1

Total number of participants analyzed in the study.

1.8%

Variance Explained by

Percentage of variance in cognitive function explained by in MarkVCID-1.

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Biological validation of peak‐width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium

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