Journal Article Ppublish
PubMed: 40465677 DOI: 10.1002/alz.70326
Assessing the Global Impact of Brain Small Vessel Disease on Cognition: The Multi-Ethnic Study of Atherosclerosis.
Alzheimers Dement 21(6):e70326
Authors: Sokratis Charisis, Tanweer Rashid, Christina Dintica, Mitzi Gonzales, Hangfan Liu, Jeffrey B Ware, Thomas R Austin, Paul N Jensen, Alison E Fohner, Jordan E Tanley, Jingzhong Ding, José A Luchsinger, Bonnie Sachs, Ilya M Nasrallah, R Nick Bryan, Kathleen M Hayden, David Wolk, Katya Rascovsky, Christos Davatzikos, William T Longstreth, Kristine Yaffe, Sudha Seshadri, Susan R Heckbert, Timothy Hughes, Mohamad Habes
Affiliations
- Neuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
- Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, California, USA.
- Department of Neurology, Cedars Sinai Medical Center, Los Angeles, California, USA.
- Center for Advanced Imaging Research (CAIR), University of Maryland School of Medicine, Baltimore, Maryland, USA.
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- Department of Epidemiology, University of Washington, Seattle, Washington, USA.
- Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
- Department of Medicine, University of Washington, Seattle, Washington, USA.
- Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
- Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, New York, USA.
- Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
- AI2D Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- Department of Social Sciences and Health Policy, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
- Alzheimer's Disease Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- Department of Neurology, University of Washington, Seattle, Washington, USA.
Abstract
INTRODUCTION
We aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.
METHODS
In 892 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we derived perivascular spaces (PVS), white matter hyperintensities (WMH), microbleeds (MB), and white matter fractional anisotropy (FA) and trace (TR). Cognitive function was assessed with a comprehensive neuropsychological battery.
RESULTS
A composite SVD measure was constructed as a linear combination of basal ganglia PVS, thalamus PVS, periventricular WMH, subcortical WMH, and white matter FA and TR, and exhibited associations with worse global and domain-specific cognitive performance. Additionally, SVD mediated the effect of age and cardiovascular disease risk on global cognitive function, both directly and through smaller gray matter (GM) volume.
DISCUSSION
Integrating multiple individual SVD endophenotypes may more accurately reflect the neurobiology of SVD and capture its global impact on cognition. SVD mediates the effects of age and cardiovascular disease risk on cognition through both atrophy-related and non-atrophy-related pathways.
HIGHLIGHTS
Associations between individual magnetic resonance imaging (MRI) markers of brain small vessel disease and cognitive outcomes might not fully capture the global impact of small vessel disease on cognition. We modeled small vessel disease as a latent construct, integrating multiple MRI endophenotypes in strategic brain regions. The small vessel disease construct was associated with worse global and domain-specific cognitive performance. The small vessel disease construct exhibited mediating effects in the relationships of aging and cardiovascular disease risk with cognition through pathways that both involve and are independent of brain atrophy. Integrating information from multiple relevant imaging endophenotypes could open new avenues in small vessel disease research, broadening our understanding of its risk factors and clinical correlates.
MeSH
White Matter, Language, Dementia, Memory, Short-Term, Atrophy, Alzheimer Disease, Aging, Brain, Cardiovascular Diseases, Multiple Chronic Conditions, Magnetic Resonance Imaging, Executive Function, Deep Learning, Diffusion Tensor Imaging, Endophenotypes, Atherosclerosis, Cerebral Small Vessel Diseases, Cognition, Negotiating