Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network.
Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=-0.063, 95% CI: -0.106, -0.020), anterior cingulate (β=-0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β=-0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=-0.024, 95% CI: -0.062, 0.014) and the hippocampus (β=-0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life.
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, 7201 Wisconsin Avenue, Room 3C309, Bethesda, MD 20814, USA. Electronic address: tad.haight@nih.gov.
Thaddeus J
TJ
Haight
Department of Radiology, University of Pennsylvania, 3600 Market St., Philadelphia, PA 19104, USA.
R Nick
RN
Bryan
Department of Radiology, University of Pennsylvania, 3600 Market St., Philadelphia, PA 19104, USA.
Guray
G
Erus
Department of Radiology, University of Pennsylvania, 3600 Market St., Philadelphia, PA 19104, USA.
Christos
C
Davatzikos
Division of Epidemiology and Community Health, University of Minnesota, 1300 S. 2nd Street, Suite 300, Minneapolis, MN, USA.
David R
DR
Jacobs
Helen Wills Neuroscience Institute, University of California-Berkeley, 132 Barker Hall, Berkeley, CA, USA.
Mark
M
D'Esposito
Department of Medicine, Division of Preventive Medicine, University of Alabama, Medical Towers 614, 1717 11th Avenue South, Birmingham, AL, USA.
Cora E
CE
Lewis
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, 7201 Wisconsin Avenue, Room 3C309, Bethesda, MD 20814, USA.
Lenore J
LJ
Launer
D000465:Algorithms; D001921:Brain / Q000503:physiopathology; D001927:Brain Diseases / Q000503:physiopathology; D062485:Breath Holding; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology* / Q000523:psychology*; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000378:metabolism / Q000503:physiopathology; D050171:Dyslipidemias / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D012307:Risk Factors
D010100:Oxygen
Alzheimer's disease; Neurophysiology; Vascular risk factors