Altered PET functional brain responses in cognitively intact elderly persons at risk for Alzheimer disease (carriers of the epsilon4 allele).
OBJECTIVE
Few previous studies have investigated the association between APOE genotype and brain activation during performance of cognitive tasks in healthy middle-aged and elderly subjects, and the results have been mixed. The authors investigated APOE-mediated differential brain activation in a group of healthy elderly subjects.


METHODS
Using H215O positron emission tomography (PET), they imaged 32 healthy subjects (26 non-epsilon4 carriers and 6 epsilon4 carriers) performing a serial shape-recognition memory task under two conditions: Simple Demand (SD), in which one shape was presented in each study trial, and Titrated Demand (TD), in which study list length was adjusted so that each subject recognized words at approximately 75% accuracy. Multiple-regression analyses were performed, with the "activation" difference (TD-SD PET counts) as the dependent variable and the APOE genotype (presence versus absence of the epsilon4 allele) as the independent variable.


RESULTS
Compared with non-carriers, epsilon4 carriers exhibited significantly decreased TD-SD activation differences in the left superior temporal, right superior frontal, left postcental, left precuneus, and posterior cingulate gyrus because epsilon4 carriers (versus non-carriers) showed increased activation during the SD and decreased activation during the TD condition.


CONCLUSIONS
Patterns of brain activation during a nonverbal memory task differed as a function of APOE genotype and, therefore, of genetic risk for Alzheimer disease (AD). Differences in activation were not a reflection of task difficulty, but indicate memory-related altered cognitive processing. Brain regions with decreased activation in the epsilon4 subjects may result from subclinical incipient AD pathology and/or APOE-related neurophysiologic heterogeneity.
Scarmeas
Nikolaos
N
Departments of Neurology,College of Physicians and Surgeons of Columbia University Medical Center; 622 West 168th St., PH 19th floor; New York, NY 10032, USA. ns257@columbia.edu
Habeck
Christian
C
Anderson
Karen E
KE
Hilton
John
J
Devanand
Davangere P
DP
Pelton
Gregory H
GH
Tabert
Matthias H
MH
Flynn
Joseph
J
Park
Aileen
A
Ciappa
Alejandra
A
Tycko
Benjamin
B
Stern
Yaakov
Y
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000502:physiology*; D049268:Positron-Emission Tomography; D012016:Reference Values; D012307:Risk Factors; D012691:Serial Learning / Q000502:physiology; D014706:Verbal Learning / Q000502:physiology*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E