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ImportancePoor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults.ObjectiveTo examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages.Design, setting, and participantsIn this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had received pseudocontinuous arterial spin labeling magnetic resonance imaging. Cardiovascular risk was measured at 5-year intervals across 5 phases from September 1991 to October 2013. Arterial spin labeling scans were acquired between April 2014 and December 2014. Data analysis was performed from June 2016 to September 2018.ExposuresFramingham Risk Score (FRS) for cardiovascular disease, comprising age, sex, high-density lipoprotein cholesterol level, total cholesterol level, systolic blood pressure, use of antihypertensive medications, cigarette smoking, and diabetes, was assessed at 5 visits.Main outcomes and measuresCerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging.ResultsOf 116 adult participants, 99 (85.3%) were men. At the first examination, mean (SD) age was 47.1 (5.0) years; at the last examination, mean (SD) age was 67.4 (4.9) years. Mean (SD) age at MRI scan was 69.3 (5.0) years. Log-FRS increased with time (B = 0.058; 95% CI, 0.044 to 0.072; P Conclusions and relevanceCardiovascular risk in midlife was significantly associated with lower gray matter perfusion at older ages, but this association was not significant for cardiovascular risk in later life. This finding could inform the timing of cardiovascular interventions so as to be optimally effective.

Original publication




Journal article


JAMA network open

Publication Date





Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.


Humans, Dementia, Cardiovascular Diseases, Spin Labels, Magnetic Resonance Imaging, Longitudinal Studies, Prospective Studies, Cerebrovascular Circulation, Socioeconomic Factors, Adult, Aged, Aged, 80 and over, Middle Aged, England, Female, Male