Abstract
BACKGROUND
Peak-width of skeletonized mean diffusivity (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 white matter hyperintensities.
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.
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This post is Copyright: Alison M. Luckey,
Saptaparni Ghosh,
Chen‐Pin Wang,
Alexa Beiser,
Rebecca Bernal,
Zhiguang Li,
Djass Mbangdadji,
Elyas Fadaee,
Haykel Snoussi,
Angel Gabriel Velarde Dediós,
Hector A. Trevino,
Monica Goss,
Laura J. Hillmer,
Christopher E. Bauer,
Adam M. Staffaroni,
Lara Stables,
Marilyn Albert,
Jayandra J. Himali,
Thomas H. Mosley,
Lars Forsberg,
Vilmundur Guðnason,
Baljeet Singh,
Herpreet Singh,
Kristin Schwab,
Joel H. Kramer,
Gary A. Rosenberg,
Karl G. Helmer,
Steven M. Greenberg,
Mohamad Habes,
Danny J. J. Wang,
Brian T. Gold,
Hanzhang Lu,
Arvind Caprihan,
Myriam Fornage,
Lenore J. Launer,
Konstantinos Arfanakis,
Sudha Seshadri,
Charles DeCarli,
Pauline Maillard,
Claudia L. Satizabal | November 21, 2024