Abstract-Hypertension appears to alter brain morphology, as well as the cerebrovascular support for information processing. Because these effects might reflect progressive effects of essential hypertension on the brain, we asked whether structural and functional brain indices would predict the success of pharmacological treatment of hypertension among 45 previously unmedicated individuals. After initial structural MRI and functional positron emission tomography imaging, subjects were randomly assigned in a double-blind fashion for treatment for 1 year with either lisinopril or atenolol. Systolic and diastolic blood pressure decreases after treatment stabilization were correlated to a pretreatment index of brain aging (combined ratings of ventricle and sulcal size and white matter hyperintensities) and the pretreatment change in regional cerebral blood flow during working memory in the thalamus and posterior parietal regions of interest. In multiple regression analyses, the structural brain index and the blood flow response in the thalamus predicted 20% of the variance in the systolic blood pressure response to treatment controlling for pretreatment blood pressure, age, gender, and type and dose of medication. Alcohol use influenced the thalamic response measure, but covariates did not alter the relation between greater indices of brain aging and less successful blood pressure response to treatment. The state of the brain may be an important factor in the remediation of blood pressure. A lthough characteristics placing a person at risk for essential hypertension are well known, predictors of blood pressure (BP) response to pharmacological treatment, other than current BP, have received less attention. 1,2 Once hypertension management has begun, appropriate clinical management and compliance with the medical regimen are clearly factors in treatment outcome. 3 In addition, different treatment approaches may be more effective with, eg, diastolic hypertension versus isolated systolic hypertension; but clear clinical evidence for this has yet to be established. 4 Cerebrovascular factors are rarely considered as central to disease diagnosis or treatment but are considered only if frank cerebrovascular disease co-occurs with hypertension. 5 Increasing evidence of central nervous system involvement as either a cause or consequence of essential hypertension, 6 -12 however, led us to ask whether brain morphological indices of brain aging or regional cerebral blood flow responsivity would predict BP decline during pharmacological treatment of essential hypertension.A number of factors suggest that cerebral structure and function might relate to success of BP treatment. First, hypertension has been characterized as accelerated aging, and aging changes in the brain are well established. [13][14][15][16] Second, hypertension has been related to changes in both brain structure and cerebrovascular responsivity during information processing. 6,9,[17][18][19] Third, hypertension in mid-to-late life is associated with mild cognit...