Independent and combined effects of hypertension and age on cognition and the cerebrovascular system in the rhesus monkey

Little is known about the effect of hypertension on cognition, nor the combined effect of hypertension and age. In order to overcome some confounding variables found in human studies including use of anti-hypertensive medication, varying definitions of hypertension, and cultural and educational biases in cognitive tests, we developed a non-human primate model of untreated hypertension.; Coarctation of the thoracic aorta induced elevated blood pressure. Thirteen young (4--7 years) and fourteen middle-aged (14--19 years) male rhesus monkeys were subdivided into unoperated (normotensive) or coarcted (hypertensive) groups producing a two by two design.; Each monkey was tested on a battery of cognitive tasks five months following the induction of hypertension. The pattern of performance suggests a dissociation between changes seen with age and those due to hypertension. Relative to young normotensive subjects, middle-aged hypertensive subjects were impaired on tasks of learning, recognition memory, spatial and object working memory span, and executive function while middle-aged normotensive and young hypertensive groups generally were not impaired.; Magnetic Resonance Imaging (MRI) with contrast agents and intravenous radioactive tracer studies were employed to assess in-vivo and ex-vivo integrity of the vascular system and blood brain barrier (BBB). Two years after entry into this study, T1 weighted serial MR images were acquired prior to and following an injection of Magnevist (gadopentate dimeglumine), a contrast agent that crosses a disrupted BBB. The volume of the Magnevist enhanced voxels was significantly greater in the middle-aged hypertensive subjects compared to the middle-aged normotensive subjects (p=0.045), providing compelling evidence that the interaction of hypertension and age alters the cerebrovasculature.; To further assess possible BBB disruptions, monkeys were injected with 14C-sucrose, a radioactive tracer. Ex-vivo analysis of brain samples failed to show evidence of tracer leakage into the brain parenchyma, suggesting the BBB is not grossly disrupted.; Collectively, these studies help isolate the individual and combined effects of age and hypertension on cognition and morphology. This non-human primate model of hypertension offers a reliable method to isolate vascular factors and better understand their effects on the brain, while retaining the ability to assess cognitive functions in parallel to those examined in humans.