Cerebrovascular support for cognitive processing in hypertensive patients is altered by blood pressure treatment

Abstract

Hypertension is associated with mild decrements in cognition. In addition, regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults, who, compared with normotensive subjects, manifest greater correlation in blood flow response across task-related brain regions. Here, we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class. Treatment with lisinopril, an angiotensin-converting enzyme blocker, known to enhance vasodilative responsivity, was compared with treatment with atenolol, a beta-blocker. Untreated hypertensive volunteers (n=28) were randomly assigned and treated for 1 year. Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide, a vasodilator, were assessed pretreatment and posttreatment. Peripheral brachial artery dilation during reactive hyperemia was also measured. Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection. Brachial artery flow-mediated dilation increased with treatment. No differences between medications were observed. In brain regions active in memory processing, however, regional cerebral blood flow responses were more highly correlated after treatment. Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension. This greater correlation among active brain regions, which is present as well in untreated hypertensive relative to normotensive volunteers, may represent compensation in the face of less region-specific responsivity in individuals with hypertension.

Figure 1

Study Design and Participant flow. Initial consent to participate was obtained from 81 volunteers. During screening and initial testing attrition occurred due to lack of interest (n=14), medical exclusion (n=18) or claustrophobia in MRI (n=4). After randomization to a drug treatment, one participant from each drug group failed to meet treatment expectations within the 1-year treatment and was withdrawn from the study. Due largely to participant refusal, arterial catheterization was not performed to obtain quantitative blood flow on 15 of the completing participants. Among those with complete blood flow data, 6 did not receive acetazolamide due either to sulfide sensitivity or inability to complete the PET session, e.g., due to back pain.

Figure 2

Scatter diagrams of the relationship between dorsolateral prefrontal and posterior parietal areas before and after treatment. Data from one extreme participant is omitted, pre treatment correlation =.61; post treatment correlation =.86.