TY - JOUR
T1 - Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease
AU - Small, Gary W.
AU - Ercoli, Linda M.
AU - Silverman, Daniel H.S.
AU - Huang, S. C.
AU - Komo, Scott
AU - Bookheimer, Susan Y.
AU - Lavretsky, Helen
AU - Miller, Karen
AU - Siddarth, Prabha
AU - Rasgon, Natalie L.
AU - Mazziotta, John C.
AU - Saxena, Sanjaya
AU - Wu, H. M.
AU - Mega, Michael S.
AU - Cummings, Jeffrey L.
AU - Saunders, Ann M.
AU - Pericak-Vance, Margaret A.
AU - Roses, Allen D.
AU - Barrio, Jorge R.
AU - Phelps, Michael E.
PY - 2000/5/23
Y1 - 2000/5/23
N2 - 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.
AB - 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.
KW - Age-associated memory impairment
KW - Apolipoprotein E
KW - Cerebral glucose metabolism
KW - Positron emission tomography
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U2 - 10.1073/pnas.090106797
DO - 10.1073/pnas.090106797
M3 - Article
C2 - 10811879
AN - SCOPUS:12944259210
VL - 97
SP - 6037
EP - 6042
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 11
ER -