This project pursues three main aims through the study of resting and activated regional cerebral blood flow (rCBF) in early and late stage Alzheimer's Disease (AD). The research is based on findings concerning cerebral activity and responsivity in sensory-motor and association cortex in AD. (1) A proposed quantitative marker for early AD, based on the ratio of RCBF in posterior temporal-parietal to that in sensory motor cortex will be evaluated in a prospective study of 60 suspected early AD patients, the stage most difficult to diagnose clinically. (2) These patients will also be used in studies attempting to """"""""capture"""""""" and investigate the period of increased cerebral response to mentally demanding tasks previously noted in a subgroup of well performing AD patients. This increased activity is hypothesized to reflect successful compensation to the degenerative processes accompanying early AD. The early AD patients will undergo successive studies of cortical flow under both simple sensory-motor tasks, aimed at preserved perirolandic cortex, and more complex cognitive tasks, aimed at association cortex. Based on previous data, approximately 75% of the patients screened are expected to become well defined AD cases, thus providing a substantial database on early changes in mild AD as well as permitting a retrospective assessment and refinement of the proposed RCBF marker. It is hypothesized that, as AD progresses, there is a curvilinear relationship between changes in performance and CBF related increases in association cortex and that decline of the activation response, following the period in which a peak occurs, signals the more debilitating stage of the disease. The end of effective compensation may mark the onset of more severe psychological and social problems as well as perhaps mark the end of a critical period during which AD is most responsive to therapeutic intervention. (3) A series of 30 moderately to severely impaired patients, recruited in prior years, will be followed into later stage AD to assess the effects of severe parenchymal degeneration on CO2 tests of vascular reactivity - especially in posterior association areas where vascular reserve appears unaffected in earlier stages of AD. This data is of potential diagnostic value in assessing dementia patients with questionable etiology. Late AD patients will also have RCBF studied during simple sensory-motor tasks to further evaluate the compensatory reactivity hypothesis in a situation where AD may be affecting rolandic cortex as well. Resting state RCBF will be measured with both 133Xe clearance and 99mTc HM-PAO SPECT. Task related activation will be assessed with 133Xe cortical flow studies. Combined, the aims offer theoretical information concerning performance changes and compensatory reactivity in degenerative dementia as well as data of clinical use in confirming early AD.
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