Gary W. Small1,2,3,4, Linda M. Ercoli2,4, Daniel Silverman2, S C Huang2, Scott Komo2,4, Susan Y. Bookheimer5,2,4, Helen Lavretsky2,4, Karen J. Miller2,4, Prabha Siddarth2,4, Natalie Rasgon2,4, John C. Mazziotta2, Sanjaya Saxena2, Hui‐Yuan Wu2, Michael S. Mega2, Jeffrey L. Cummings2,4, Ann M. Saunders2, Margaret A. Pericak‐Vance2, Tommy Martinsson2,4, Jorge R. Barrio2,4, Michael E. Phelps2
1Center on Aging and
2Center on Aging and Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024; Departments of Molecular and Medical Pharmacology and Neurology, and Brain Mapping Center, University of California, Los Angeles, CA 90095; Department of Medicine, Duke University Medical Center, Durham, NC 27710; and Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709
3Department of Medicine, Duke University Medical Center, Durham, NC 27710; and
4Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709
5Brain Mapping Center, University of California, Los Angeles, CA 90095;
Tóm tắt
The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.
