Neuropathology of progressive cognitive decline in chronically hypertensive rhesus monkeys

Hypertension is an identified major risk factor for cerebrovascular disease, which is second only to Alzheimer's disease as a cause of dementia in the elderly. In addition, hypertension has been associated with a more subtle, progressive decline in cognitive function for which the neuropathology is not well understood. The present study was undertaken to explore this relationship in an experimental, nonhuman primate model, with hypertension produced by a coarctation of the thoracic aorta. Since prior studies with this model have shown a progressive decline in memory function, similar to that seen in human hypertension, as well as scattered microinfarcts in the cerebral white and gray matter, this study was designed to explore the relationship between these two. In addition to microinfarcts, the hypertensive monkeys with the highest arterial blood pressure also showed minute areas of focal gliosis without infarction. The number of these focal lesions showed a significant correlation with the severity of the hypertension, but not with the behavioral deficit. For four of these hypertensive monkeys, immunostaining demonstrated a pervasive, widespread activation of microglial cells and astroglial cells in the white matter as well as evidence of leaks in the blood-brain barrier, providing a more logical substrate for the cognitive decline.