title: Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.
abstract: 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.
authors.affiliation: Center on Aging and Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024, USA. gsmall@mednet.ucla.edu
authors.forename: G W
authors.initials: GW
authors.lastname: Small
authors.forename: L M
authors.initials: LM
authors.lastname: Ercoli
authors.forename: D H
authors.initials: DH
authors.lastname: Silverman
authors.forename: S C
authors.initials: SC
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Komo
authors.forename: S Y
authors.initials: SY
authors.lastname: Bookheimer
authors.forename: H
authors.initials: H
authors.lastname: Lavretsky
authors.forename: K
authors.initials: K
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Siddarth
authors.forename: N L
authors.initials: NL
authors.lastname: Rasgon
authors.forename: J C
authors.initials: JC
authors.lastname: Mazziotta
authors.forename: S
authors.initials: S
authors.lastname: Saxena
authors.forename: H M
authors.initials: HM
authors.lastname: Wu
authors.forename: M S
authors.initials: MS
authors.lastname: Mega
authors.forename: J L
authors.initials: JL
authors.lastname: Cummings
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
authors.forename: M E
authors.initials: ME
authors.lastname: Phelps
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D011581:Psychological Tests; D012307:Risk Factors; D014055:Tomography, Emission-Computed
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E