title: APOE modifies the association between Aβ load and cognition in cognitively normal older adults.
abstract: OBJECTIVE
  To determine the relationship between β-amyloid (Aβ) load as measured by [(11)C]-Pittsburgh compound B (PiB) PET and cognitive function in cognitively normal older adults.
  
  
  METHODS
  We studied 408 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through March 2011. The participants underwent PiB PET and neuropsychometric testing within 6 months. The association between PiB retention and cognitive function was measured by partial correlation and an interaction with APOE status was tested using linear regression after adjusting for age, sex, and education.
  
  
  RESULTS
  Higher PiB retention was associated with cognitive performance (Spearman partial r = -0.18; p < 0.01), specifically the memory, language, attention/executive, and visual-spatial processing domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status on linear regression analysis even after controlling for the differences in the distribution of PiB values among APOE ε4 carriers and noncarriers (p = 0.02). Cognitive performance was associated with the Aβ deposition in the frontal, temporal, and parietal lobe association cortices in APOE ε4 carriers on SPM analysis (p < 0.001).
  
  
  CONCLUSIONS
  There is a modest association between PiB retention and cognitive function in cognitively normal older adults and this relationship between Aβ load and cognitive function is modified by APOE status. Whereas Aβ load is associated with greater cognitive impairment in APOE ε4 carriers, the cognitive function in APOE ε4 noncarriers is influenced less by the Aβ load, suggesting that APOE isoforms modulate the harmful effects of Aβ on cognitive function.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA. kantarci.kejal@mayo.edu
authors.forename: K
authors.initials: K
authors.lastname: Kantarci
authors.forename: V
authors.initials: V
authors.lastname: Lowe
authors.forename: S A
authors.initials: SA
authors.lastname: Przybelski
authors.forename: S D
authors.initials: SD
authors.lastname: Weigand
authors.forename: M L
authors.initials: ML
authors.lastname: Senjem
authors.forename: R J
authors.initials: RJ
authors.lastname: Ivnik
authors.forename: G M
authors.initials: GM
authors.lastname: Preboske
authors.forename: R
authors.initials: R
authors.lastname: Roberts
authors.forename: Y E
authors.initials: YE
authors.lastname: Geda
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D056344:Executive Function / Q000502:physiology; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011597:Psychomotor Performance / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E