Effects of hypertension and age on cerebrovasculature and cognition in the monkey
Farris, Chad William
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Cognitive impairments in memory and executive function are commonly observed with aging in humans. Age-related cognitive decline is exacerbated by hypertension, but it is less clear whether hypertension can lead to cognitive impairment in young adults. Rhesus monkeys evidence cognitive impairment with age that parallels that seen in humans and have been established as an appropriate animal model to examine the neurobiological basis of age-related cognitive decline. The development of a technique to produce chronic hypertension in the monkey has permitted the expansion of this model to evaluate the effects of hypertension in both young adult and aged monkeys. We used this model to examine whether hypertension alone is sufficient to cause impairment in learning and memory in the young adult. In order to gain a better understanding of the etiology of cognitive decline with hypertension or age, we then evaluated the integrity of cerebral microvasculature in hypertensive and in aged cognitively characterized rhesus monkeys using magnetic resonance imaging to measure cerebral blood volume (CBV) and image analysis on serial brain sections immunohistochemically stained for type IV collagen to quantify the microvasculature. Lastly, we utilized dynamic R2-star mapping to assess hippocampal vasoreactivity to carbon dioxide challenge from early adulthood to old age. The results demonstrated that induction of hypertension in young adult monkeys impaired relearning of a previously learned rule, but not visual recognition memory. Morphological measurement showed an increase in vascularity of the cingulum bundle with age but not in three other preselected areas, but this change did not correlate with cognitive impairments. MRI measurement of CBV in gray matter increased with duration of hypertension, but did not correlate with cognitive function. Functional vasoreactivity to carbon dioxide challenge was reduced in the right hippocampus, but not the left with age. The right hippocampal vasoreactivity, but not left, correlated with performance on two of three hippocampal dependent memory tasks in middle-aged animals. Together, the results of these studies suggest that hypertension in young adulthood can impair some aspects of cognition, and while both structural and functional microvascular alterations occur with aging or hypertension, only functional alterations correlate with cognitive function.
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