THE AGING RHESUS MONKEY: PATTERNS OF COGNITIVE IMPAIRMENT IN NORMAL AGING AND CEREBROVASCULAR DISEASE
M.B. MOSS
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118
It is only in the last 25 years that significant strides have been taken toward the development of primate models of normal human aging and age-related disease. Together with advances in the fields of molecular biology, neuroimaging and behavioral neuroscience, these models have emerged as potentially important components in our understanding of the age-related cognitive decline in humans. This presentation will cover recent advances from two research programs in our Department that are aimed toward the understanding of the neural basis of cognitive decline that occurs in normal aging and in hypertensive cerebrovascular disease. As a core component of our studies in a primate model of normal aging, we have assessed monkeys ranging from 5 to 35 years of age on a battery of neuropsychological tests adapted from those used in human studies. These include tasks of visual recogntion memory, spatial memory and executive system function. Groups are stratified into young adults (5-9 yrs), late middle aged (15-19 yrs), early senescent (20-24 yrs), advanced aged (25-29yrs) and the oldest old (30+ yrs) and a profile of cognitive function is determined for each age group. In addition to obtaining a cognitive profile across cognitve domains for each age group , using a core set of behavioral measures and prinicipal component analyses, we have established a composite score of cogntive function for each animal in our study. The findings to date indicate that not only is aging accompanied by a decline in overall cognitive function, but also that the profile of impairment changes with age. The overall scores are also used to assess possible relationships with a series of other neurobiological outcome variables. We have conducted similar behavioral studies in our model of hypertensive cerebrovascular disease. The model is based on human epidemiological studies showing that the incidence of hypertension in the adult population of the United States is approximatly 25% affecting over 60 million people and that the incidence of hypertension increases with age to the extent that nearly 2 of evey 3 people over the age of 65 may evidence this condition. We assessed the effects of hypertension on memory function in a group of adult male rhesus monkeys with hypertension that was induced by surgical coarctation of the thoracic aorta. Based on direct arterial blood pressure measurements, hypertensive monkeys were classified as having either significant hypertension (systolic pressure >150mm/Hg) or borderline hypertension (135 to 149 mm/Hg). The main finding of this study demonstrated that significant hypertension, but not borderline hypertension in otherwise healthy young adult monkeys, produces a significant and progressive impairment in memory function. Our studies in both programs have led to some intriguing notions about the role of inflammation in cognitive decline in both normal aging and hypertensive cerebrovascular disease. (Supported by NIH grants R37-AG17609 and P01-AG00001).
Key words:
primate, memory, aging, hypertension, cognition
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