Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.
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.
Small, GW; Ercoli, LM; Silverman, DH; Huang, SC; Komo, S; Bookheimer, SY; Lavretsky, H; Miller, K; Siddarth, P; Rasgon, NL; Mazziotta, JC; Saxena, S; Wu, HM; Mega, MS; Cummings, JL; Saunders, AM; Pericak-Vance, MA; Roses, AD; Barrio, JR; Phelps, ME
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