MacIntosh BJ, Shirzadi Z, Atwi S, et al. - In this cross-sectional study, researchers examined the contributions of metabolic and vascular risk factors (MVRFs) to regional cerebral blood flow (CBF) and verbal learning & memory among middle-aged adults. Partial least squares (PLS) analysis was used to develop latent risk factor profiles and investigate their correlations to CBF in 93 regions of interest among 451 individuals of the Coronary Artery Risk Development in Young Adults. This multivariate analysis exhibited relative to obesity (higher BMI and waist circumference), dysregulated glucose homeostasis (higher fasting glucose, oral glucose tolerance, and higher fasting insulin), and adverse fasting lipid profile (lower high-density lipoprotein cholesterol and higher triglycerides), regional CBF was lower. It was discovered in a sensitivity analysis that important associations between MVRFs and CBF were significant in the hypertension-medicated subgroup. In a mediation model, the PLS-based MVRFs profile was related to memory performance (rey auditory verbal learning test), nevertheless, CBF was not an important mediator of this correlation. Thus, the results define an adverse midlife metabolic profile that may make the stage for incipient dementia and add to widespread variations in CBF.