Identification of Alzheimer disease risk by functional magnetic resonance imaging.
BACKGROUND
Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials.


OBJECTIVE
To determine whether functional magnetic resonance imaging can reliably distinguish risk groups for AD among cognitively normal middle-aged adults.


METHODS
Cross-sectional case-control study.


METHODS
University of California, San Diego, Alzheimer Disease Research Center participants and San Diego community volunteers.


METHODS
Twenty cognitively normal individuals (10 high risk and 10 low risk), aged 58 to 65 years, were divided into 2 groups based on the presence or absence of the apolipoprotein E epsilon4 allele and a positive family history of AD.


METHODS
Word pairs were presented in a blocked design alternating between conditions of novel pairs, repeated pairs, and fixation. Whole-brain differences in blood oxygenation level-dependent brain responses between conditions were compared across risk groups.


RESULTS
Compared with the low-risk group, the high-risk group showed many areas of differential blood oxygenation level-dependent response in regions commonly associated with AD pathology (eg, the left medial temporal lobe). Furthermore, different patterns of association between left medial temporal lobe activity and memory performance were demonstrated.


CONCLUSIONS
Results support a theory of up-regulation in neuronal memory systems in people at risk for AD many years before the typical age at disease onset. They further demonstrate that functional magnetic resonance imaging is a viable technique to identify persons at risk for AD.
Fleisher
Adam S
AS
Department of Neurosciences, University of California, San Diego, La Jolla 92037, USA. afleisher@ucsd.edu
Houston
Wes S
WS
Eyler
Lisa T
LT
Frye
Susan
S
Jenkins
Cecily
C
Thal
Leon J
LJ
Bondi
Mark W
MW
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000502:physiology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000592:standards* / Q000639:trends; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000175:diagnosis / Q000503:physiopathology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D015854:Up-Regulation / Q000502:physiology