title: fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.
abstract: OBJECTIVE
  To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults.
  
  
  METHODS
  Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE epsilon4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions.
  
  
  RESULTS
  Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated.
  
  
  CONCLUSIONS
  The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.
authors.affiliation: University of California San Diego and VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. mbondi@ucsd.edu
authors.forename: Mark W
authors.initials: MW
authors.lastname: Bondi
authors.forename: Wes S
authors.initials: WS
authors.lastname: Houston
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Brown
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002540:Cerebral Cortex / Q000098:blood supply / Q000502:physiology*; D002560:Cerebrovascular Circulation; D003071:Cognition; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006624:Hippocampus / Q000098:blood supply / Q000502:physiology*; D006801:Humans; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D009483:Neuropsychological Tests; D010775:Photic Stimulation; D011379:Prognosis; D012016:Reference Values
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E