Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults

Abstract

Background and purpose: The purpose of this study was to investigate whether the Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness are associated with cortical volume and thickness.

Methods: Consecutive subjects participating in a prospective cohort study of aging and mild cognitive impairment enriched for vascular risk factors for atherosclerosis underwent structural MRI scans at 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). Multiple linear regression was used to determine the association of Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness with cortical volume and thickness.

Results: One hundred fifty-two subjects (82 men) were aged 78 (±7) years, 94 had a clinical dementia rating of 0, 58 had a clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was 28±2. Framingham Cardiovascular Risk Profile score was inversely associated with total gray matter volume and parietal and temporal gray matter volume (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely associated with parietal and total cerebral gray matter thickness (adjusted P<0.03). Carotid artery intima-media thickness was inversely associated with thickness of parietal gray matter only (adjusted P=0.04). Including history of myocardial infarction or stroke and radiological evidence of brain infarction, or apolipoprotein E genotype did not alter relationships with Framingham Cardiovascular Risk Profile or carotid artery intima-media thickness.

Conclusions: Increased cardiovascular risk was associated with reduced gray matter volume and thickness in regions also affected by Alzheimer disease independent of infarcts and apolipoprotein E genotype. These results suggest a "double hit" toward developing dementia when someone with incipient Alzheimer disease also has high cardiovascular risk.

Figure 1

Scatterplots showing the relationships between Freesurfer regional volumes and FCRP. FCRP and volumes were regressed on age, gender, magnet strength, intracranial volume, and cognitive status, and the residuals were plotted against each other. The slope of the line of best fit is the same as the regression coefficient for FCRP in the linear models that included history and evidence of vascular injury. When there are significant differences due to evidence and/or history of vascular injury, regression lines offset by the estimated difference are plotted. A: FCRP and parietal gray matter volume, illustrating effect of history of vascular injury, evidence of vascular injury, and combined effect of history and evidence of vascular injury. B: FCRP and total gray matter volume, illustrating effect of history of vascular injury.