Normal human aging is typically characterized by a mild decline in cognition, particularly for memory and executive system function. Of interest, some individuals evidence virtually no change in cognition with age. Others evidence a marked decline, but not to the level of Alzheimer's disease or other dementia state. To date, the neurobiological basis of so called """"""""successful"""""""" vs. """"""""unsuccessful"""""""" aging remains unclear. The cumulative findings from this program have moved us closer to the belief that the degradation of forebrain white matter may play the key role in the cognitive decline of normal aging. Accordingly, Project 1 will continue to serve two roles: In the first, we will continue using a comprehensive set of tasks to assess cognition in our cohort of 42 monkeys (12 young, 18 middle aged and 12 old) using a cross-sectional design. This will allow us to help identify not only the emergence of the initial impairment in cognition, but in consort with the other 3 projects, to narrow our search for the neurobiological alterations that underlie these cognitive changes. In our second role, we will conduct, for the first time we believe, a behavioral longitudinal study in the aged rhesus monkey. Early middle age monkeys (N=12) will be tested at six time points over a period of 4.5 yrs when they reach at age of 18-20 years (a time frame roughly equivalent to 14 human years) This range covers a point when monkeys evidence no impairment to a point when 2/3 show either mild or marked impairment. This will allow us to track the natural history of cognitive decline and permit the unique opportunity to assess retrograde memory loss and its relationship to anterograde memory and new learning, an important but difficult variable to assess in human aging research. Volumetric MRI, DTI, CSF, and other measures will be conducted in parallel to identify in vivo, possible neurobiologic correlates of decline. The proposed longitudinal study is also an important first step for possible future intervention studies that will target pathogenic proteins and genes now being identified in the aging brain.
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