The goal of this project is to understand how changes in the functional integrity of specific memory systems account for age-related changes in memory abilities that ultimately manifest themselves in Alzheimer's disease (AD). We hypothesize that (a) healthy aging involves a life-long decline in the function of a fronto-striatal memory system critical for perceptual- motor speed, executive components of working memory, and strategic memory performance; (b) mild cognitive impairment in aging involves late-onset declines in the functions of a medial temporal-lobe memory system critical for declarative/explicit memory performance; (c) AD involves further decline in the medial temporal-lobe memory system; and (d) aging and AD do not affect an occipital-lobe memory system that mediate visual implicit memory. To test the specific brain-behavior predictions of this theoretical framework, we shall identify 32 subjects in each of four groups: (a) younger subjects ages 30-50; (b) 65-older with intact cognitive function; (c) 65-older with mild cognitive impairment; 9d) 65- older a=with early-stage AD. Subjects will be selected from a well- characterized cohort of male and female members of Catholic religious orders who have consented to annual neurological and neuropsychological examinations and to brain autopsy in the event of death. Subjects will be given a set of memory tasks that probe the functional integrity of the three memory systems. Also, frontal-lobe and hippocampal function will be measured directly by functional magnetic resonance scanning (fMRI) as subjects perform memory asks. These studies will provide some of the first direct evidence about the brain-behavior basis of changes in memory performance due to healthy or diseased aging. Also, they provide an opportunity to discern nascent AD at a time when the disease may be treatable.
Showing the most recent 10 out of 197 publications
