Association of Lacunes with Risk Factors, Cognition, and Atrophy: The Multi-Ethnic Study of Atherosclerosis (MESA).
Authors
Affiliations (13)
Affiliations (13)
- 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.
- Department of Neurology, University of Miami, Miami, Florida.
- Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
- Harvard Medical School, Boston, Massachusetts.
- Department of Neurology, UCLA David Geffen School of Medicine and West LA Veterans Affairs Medical Center, Los Angeles, California.
- Department of Epidemiology, University of Washington, Seattle, Washington.
- AI2D Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia.
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
- Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
- Department of Neurology, University of Washington, Seattle, Washington.
- Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
- Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas.
Abstract
Lacunes are 3-15 mm cavities originating from small perforating artery disease and are a hallmark of cerebral small vessel disease (cSVD). Prior prevalence studies relied on manual rating, which is prone to inter-rater variability and cannot quantify volume. We applied deep learning to quantify lacunes in a diverse community-based cohort. In this cross-sectional analysis of 1,038 Multi-Ethnic Study of Atherosclerosis (MESA) participants, with longitudinal cognitive follow-up, we quantified lacunes, confirmed them with a trained rater, and classified them as deep or lobar. Regression models examined associations of lacunes with cardiovascular risk factors, other small vessel disease lesions, brain atrophy, and cognition. Structural equation modeling evaluated whether deep lacune burden mediated associations of age or Framingham All-Cardiovascular Disease (CVD) Risk Score with atrophy and cognition. Overall, 182 participants (17.5%) had at least one lacune (deep: 9.2%; lobar: 9.6%). Hispanic participants had lower lacune burden than White participants. Age, Framingham All-CVD Risk Score, PREVENT 10-year Total CVD Risk Score, and hypertension were associated with overall and deep lacunes, while lobar lacunes showed no associations. Deep lacunes were associated with white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds, as well as SPARE-BA, SPARE-AD, and cortical and hippocampal atrophy. Deep lacunes were cross-sectionally associated with decreased global cognition and language/semantic performance, and longitudinally with accelerated executive function decline independent of count. Deep lacune burden significantly mediated associations of age and Framingham All-CVD Risk Score with SPARE-AD, SPARE-BA, and global cognition. In this multi-ethnic community-based cohort, deep lacune burden demonstrated stronger associations with vascular risk, other cerebral small vessel disease markers, brain atrophy, and longitudinal executive function decline than lobar burden. By providing a continuous measure of lesion volume, automated quantification captured information beyond lacune count.