CEREBROVASCULAR FUNCTION IN AGING AND ALZHEIMER'S DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The aim of this pilot study is to test the central hypothesis that cerebrovascular function is compromised in patients at the early state of Alzheimer's disease (AD) as compared to healthy subjects of the same age. Specifically, we will test the following hypotheses: (1) Cerebral autoregulation, as quantified by changes in cerebral blood flow in response to changes in arterial pressure, is impaired in patients with AD. (2) Brain oxidative metabolic reserve, as quantified by the magnitude of increase in oxygen extraction fraction (OEF) in response to acute brain hypoperfusion, is attenuated in patients at the early stage of Alzheimer's disease. RESEARCH PLAN AND METHODS: This pilot study will explore specifically (1) whether cerebral autoregulation, brain oxidative metabolic reserve, and the brain neuronal activation-blood flow coupling relationship are impaired in patients at the early stage of AD, and (2) whether cerebrovascular function deteriorates rapidly associated with rapid cognitive decline observed in these patients. Twelve subjects (4 each early AD, healthy elderly, and healthy young) will be studied. 3D Magnetic Resonance images (MRI) will be acquired using a GE/Elscint Prestige 2-Tesla system. Positron emission tomography (PET) images will be acquired using a CTI Siemens HR+ whole body PET scanner in 3D mode. Cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen will be measured. CLINCAL RELEVANCE: Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting millions of the elderly in the United States and around the world. Research into mechanisms of the disease may lead to better diagnosis and treatment for these individuals.