Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease

Gary W. Small, Linda M. Ercoli, Daniel H.S. Silverman, S. C. Huang, Scott Komo, Susan Y. Bookheimer, Helen Lavretsky, Karen Miller, Prabha Siddarth, Natalie L. Rasgon, John C. Mazziotta, Sanjaya Saxena, H. M. Wu, Michael S. Mega, Jeffrey L. Cummings, Ann M. Saunders, Margaret A. Pericak-Vance, Allen D. Roses, Jorge R. Barrio, Michael E. Phelps

Research output: Contribution to journalArticlepeer-review

644 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6037-6042
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
StatePublished - May 23 2000
Externally publishedYes


  • Age-associated memory impairment
  • Apolipoprotein E
  • Cerebral glucose metabolism
  • Positron emission tomography

ASJC Scopus subject areas

  • Genetics
  • General


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