Hypertension is associated with cognitive decline in elderly persons. We studied asymptomatic hypertensive subjects using brain magnetic resonance (MR) spectroscopy to evaluate metabolite impairments before the appearance of symptoms in patients with different treatment outcomes. In all, 14 healthy controls and 37 asymptomatic hypertensive patients (17 controlled and 20 resistant) underwent brain structural MR and MR spectroscopy of the posterior paralimbic (PPL) area and left frontal white matter. Ischemic burden (IB), global cortical atrophy and microbleeds were analyzed with visual scales. Metabolite ratios involving N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (mI) were computed. Ultrasound measurements, including intima-media thickness, plaques and hemodynamic ratios, were obtained. Intergroup differences in IB, atrophy and metabolite ratios, and the atrophy and IB relationship were assessed with parametric and nonparametric statistical tests. In addition, the impacts of demographic, analytic and clinical factors, ischemia and atrophy, and ultrasound measurements on metabolite ratios were assessed. The significance level was set at P<or=0.05. Higher atrophy scores presented with higher total or frontal IB (P<0.05). However, there was no intergroup difference in atrophy and IB. PPL mI/Cr was increased in resistant hypertension (P<0.021), whereas frontal NAA/Cr (P<0.007) showed opposite trends between controlled (increased ratios) and resistant (decreased ratios) hypertension. Unlike PPL mI/Cr, frontal NAA/Cr showed significant correlations with the lipid profile and ultrasound measurements. PPL mI/Cr increases in resistant hypertension, and frontal NAA/Cr diverges between controlled and resistant hypertension before physical and neuropsychological symptoms appear.