Wendy Wang1, Faye L Norby2, Alvaro Alonso3, Rebecca F Gottesman4, Clifford R Jack5, Michelle L Meyer6, David S Knopman7, Kevin J Sullivan8, Timothy M Hughes9, Kamakshi Lakshminarayan10, Pamela L Lutsey11. 1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States. Electronic address: wang5694@umn.edu. 2. Center for Cardiac Arrest Prevention, Department of Cardiology, Cedars-Sinai Smidt Heart Institute, Los Angeles, California, United States. Electronic address: faye.norby@cshs.org. 3. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States. Electronic address: alvaro.alonso@emory.edu. 4. Department of Neurology, Johns Hopkins University, Baltimore, Maryland, United States. Electronic address: rgottesm@jhmi.edu. 5. Department of Radiology, Mayo Clinic, Rochester, Minnesota. Electronic address: jack.clifford@mayo.edu. 6. Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States. Electronic address: michelle_meyer@med.unc.edu. 7. Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States. Electronic address: knopman@mayo.edu. 8. Department of Medicine: The MIND Center, University of Mississippi Medical Center, Jackson, Mississippi, United States. Electronic address: ksullivan3@umc.edu. 9. Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States. Electronic address: tmhughes@wakehealth.edu. 10. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, United States. Electronic address: laksh004@umn.edu. 11. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States. Electronic address: lutsey@umn.edu.
Abstract
OBJECTIVE: Elevated carotid intima-media thickness (cIMT) and carotid plaque are markers of arterial injury and may be linked to structural brain injury. We hypothesized cIMT or presence of carotid plaque at midlife are associated with presence of infarcts and cerebral microbleeds, greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late-life. METHODS: We included 1,795 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 57±6 years, 57% female, 23% Black) with carotid ultrasounds in 1990-1992 and brain MRI scans in 2011-2013. Weighted linear regression was used for brain volume outcomes, while logistic regression was used for infarcts and cerebral microbleeds. RESULTS: After multivariable adjustments, the highest cIMT quintile was associated with smaller deep gray matter (β [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (β [95% CI]: -0.10 [-0.20, -0.01]) in late-life. Similarly, those with carotid plaque had smaller regional brain volumes than those without (βs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep gray matter and temporal-parietal meta ROI). No significant relations were observed with WMH volume, infarcts, or cerebral microbleeds. CONCLUSION: Over a median follow-up of 21 years, greater midlife cIMT and presence of carotid plaque were associated with smaller deep gray matter volume and cortical volume in a meta ROI involving temporal and parietal lobe regions typically involved in neurodegeneration, including Alzheimer's disease, in later life. Contrary to our hypothesis, associations between measures of arterial injury and markers of vascular brain injury were null.
OBJECTIVE: Elevated carotid intima-media thickness (cIMT) and carotid plaque are markers of arterial injury and may be linked to structural brain injury. We hypothesized cIMT or presence of carotid plaque at midlife are associated with presence of infarcts and cerebral microbleeds, greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late-life. METHODS: We included 1,795 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 57±6 years, 57% female, 23% Black) with carotid ultrasounds in 1990-1992 and brain MRI scans in 2011-2013. Weighted linear regression was used for brain volume outcomes, while logistic regression was used for infarcts and cerebral microbleeds. RESULTS: After multivariable adjustments, the highest cIMT quintile was associated with smaller deep gray matter (β [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (β [95% CI]: -0.10 [-0.20, -0.01]) in late-life. Similarly, those with carotid plaque had smaller regional brain volumes than those without (βs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep gray matter and temporal-parietal meta ROI). No significant relations were observed with WMH volume, infarcts, or cerebral microbleeds. CONCLUSION: Over a median follow-up of 21 years, greater midlife cIMT and presence of carotid plaque were associated with smaller deep gray matter volume and cortical volume in a meta ROI involving temporal and parietal lobe regions typically involved in neurodegeneration, including Alzheimer's disease, in later life. Contrary to our hypothesis, associations between measures of arterial injury and markers of vascular brain injury were null.
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