Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P=0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P=0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife.

The catechol-o-methyltransferase Val158 Met polymorphism modulates organization of regional cerebral blood flow response to working memory in adults.

This study examined the effect of catechol-o-methyltransferase (COMT) Val(158)Met genotypes on the co-activation of brain areas involved in cognition during a working memory (WM) task. The pattern of concomitant region of interest (ROI) activation during WM performance varied by genotype: Val/Val showing the least and Met/Met the most covariance. There were no differences of performance on the WM task between the COMT genotypes. However, relatively better performance was associated with less concomitance of dorsolateral prefrontal cortex (DLPFC) and cingulate cortex for Val/Val, but more concomitance of DLPFC with AH for Met/Met. Within genotypes WM performance was significantly correlated with rCBF to the amygdala/hippocampus (AH) for Val/Val (r = 0.44, p = 0.009), to the parietal lobe for Val/Met (r = 0.29, p = 0.03), and to the thalamus for Met/Met (r = 0.32, p = 0.04). Different genotypes showed different regional specificity and concomitant activation patterns suggesting that varying dopamine availability induces different brain processing pathways to achieve similar WM performance.

Use of total cerebral blood flow as an imaging biomarker of known cardiovascular risks.

BACKGROUND AND PURPOSE: This study examined whether overall cerebral blood flow was associated with known vascular risk factors, including cardiometabolic risk factors that comprise the metabolic syndrome, carotid artery intima-media thickness, and the Framingham risk score. METHODS: Three separate samples were available for analysis. Two comparable samples were combined to form a primary sample of middle-aged participants (n=576; 30-55 years of age) that completed both a risk factor assessment and a resting brain scan. Samples were recruited via mailings and advertisements within an urban area. Quantitative measures of cerebral blood flow were derived from arterial spin-labeled MRI in this sample and in a validation/generalization sample (n=76; 30-55 years). RESULTS: Cerebral blood flow was inversely associated with cardiometabolic risk indices, that is, associated with lower waist circumference, systolic blood pressure, glucose, and triglyceride and high-density lipoprotein. Moreover, cerebral blood flow was also related to Framingham risk and carotid intima-media thickness. In the validation sample, which used a slightly different brain imaging technique, significant relationships were replicated for cardiometabolic risk, but not for Framingham risk. CONCLUSIONS: Reduced cerebral blood flow seems to be a correlate of vascular disease risk factors associated with cardiometabolic dysregulation. Cerebral blood flow may provide a valid imaging biomarker for cardiovascular risk.

From Brain to Behavior: Hypertension's Modulation of Cognition and Affect.

Accumulating evidence from animal models and human studies of essential hypertension suggest that brain regulation of the vasculature is impacted by the disease. Human neuroimaging findings suggest that the brain may be an early target of the disease. This observation reinforces earlier research suggesting that psychological factors may be one of the many contributory factors to the initiation of the disease. Alternatively or in addition, initial blood pressure increases may impact cognitive and/or affective function. Evidence for an impact of blood pressure on the perception and experience of affect is reviewed vis-a-vis brain imaging findings suggesting that such involvement in hypertensive individuals is likely.