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
G W
GW
Center on Aging and Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024, USA. gsmall@mednet.ucla.edu
Ercoli
L M
LM
Silverman
D H
DH
Huang
S C
SC
Komo
S
S
Bookheimer
S Y
SY
Lavretsky
H
H
Miller
K
K
Siddarth
P
P
Rasgon
N L
NL
Mazziotta
J C
JC
Saxena
S
S
Wu
H M
HM
Mega
M S
MS
Cummings
J L
JL
Saunders
A M
AM
Pericak-Vance
M A
MA
Roses
A D
AD
Barrio
J R
JR
Phelps
M E
ME
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
D053327:Apolipoprotein E4; D001057:Apolipoproteins E