PET Scan of Brain Metabolism in Relation to Age and Disease

The Brain Physiology and Metabolism Section (BPMS) of the National Institute on Aging (NIA) and the Clinical Neuroscience Program (CNP) of the National Institute of Neurological Disorders and Stroke (NINDS) propose to study regional brain phospholipid metabolism in young and old normal volunteers and in patients with Alzheimer disease. The method to be employed, developed from animal studies, involves the intravenous injection of a radiolabeled polyunsaturated fatty acid, \[11C\]arachidonic acid and measuring regional brain radioactivity using positron emission tomography (PET). A mathematical model is used to calculate regional brain incorporation coefficients k\* of \[11C\]arachidonate into brain. These reflect brain signal transduction and membrane turnover involving phospholipids and the signal transduction and membrane turnover involving phospholipids and the activation of the enzyme, phospholipase A2. PET also will be used in the same subjects to measure regional cerebral blood flow (rCBF), a marker of brain energy metabolism, with radioactive water (\[150\]H20). The literature reports that rCBF and energy metabolism decline with age and are markedly reduced in Alzheimer disease. We hypothesize that (a) we will be able to quantify and image incorporation of \[11C\]arachidonate into the human brain for the first time, (b) in normal volunteers, k\* for arachidonate will be correlated on a regional basis with rCBF, (c) rCBF will be reduced in the older compared with the younger normal volunteers, and markedly reduced in Alzheimer disease patients compared with the older volunteers (controls), (d) the normal coupling (regression) relation between k\* and rCBF will be disturbed in Alzheimer disease. This protocol originally proposed to measure brain incorporation of two labeled fatty acids, \[11C\]arachidonate and \[11C\]palmitate, as well as rCBF, in young and old normal volunteers, and in patients with Alzheimer disease, Niemann-Pick Type C disease and brain tumors. Eleven patients with Alzheimer disease have been scanned using \[11C\]arachidonate and \[150\]H20, compared with 10 volunteers. The current amendment proposes to use only \[11C\]arachidonate and \[150\]H20 in 16 additional normal volunteers, and to compare the results between old and young groups and patients with Alzheimer disease. A request to study only 16 additional normal volunteers was approved by the NINDS IRB at the Continuing Review in 1999, and has not changed since then.