TY - JOUR
T1 - Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker
T2 - The MarkVCID Consortium
AU - Luckey, Alison M.
AU - Ghosh, Saptaparni
AU - Wang, Chen Pin
AU - Beiser, Alexa
AU - Bernal, Rebecca
AU - Li, Zhiguang
AU - Mbangdadji, Djass
AU - Fadaee, Elyas
AU - Snoussi, Haykel
AU - Dediós, Angel Gabriel Velarde
AU - Trevino, Hector A.
AU - Goss, Monica
AU - Hillmer, Laura J.
AU - Bauer, Christopher E.
AU - Staffaroni, Adam M.
AU - Stables, Lara
AU - Albert, Marilyn
AU - Himali, Jayandra J.
AU - Mosley, Thomas H.
AU - Forsberg, Lars
AU - Guðnason, Vilmundur
AU - Singh, Baljeet
AU - Singh, Herpreet
AU - Schwab, Kristin
AU - Kramer, Joel H.
AU - Rosenberg, Gary A.
AU - Helmer, Karl G.
AU - Greenberg, Steven M.
AU - Habes, Mohamad
AU - Wang, Danny J.J.
AU - Gold, Brian T.
AU - Lu, Hanzhang
AU - Caprihan, Arvind
AU - Fornage, Myriam
AU - Launer, Lenore J.
AU - Arfanakis, Konstantinos
AU - Seshadri, Sudha
AU - DeCarli, Charles
AU - Maillard, Pauline
AU - Satizabal, Claudia L.
N1 - Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - biomarker
KW - cognitive impairment
KW - diffusion tensor imaging
KW - peak-width of skeletonized mean diffusivity
KW - small vessel disease
KW - vascular contributions to cognitive impairment and dementia
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U2 - 10.1002/alz.14345
DO - 10.1002/alz.14345
M3 - Article
C2 - 39569745
AN - SCOPUS:85210024363
SN - 1552-5260
VL - 20
SP - 8814
EP - 8824
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 12
ER -