APOE modifies the association between Aβ load and cognition in cognitively normal older adults

Kejal M Kantarci, Val Lowe, S. A. Przybelski, S. D. Weigand, M. L. Senjem, R. J. Ivnik, G. M. Preboske, Rosebud O Roberts, Yonas Endale Geda, Bradley F Boeve, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack

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Abstract

Objective: To determine the relationship between β-amyloid (Aβ) load as measured by [ 11C]- 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)232-240
Number of pages9
JournalNeurology
Volume78
Issue number4
DOIs
StatePublished - Jan 24 2012

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Cognition
Linear Models
Parietal Lobe
Sex Education
Frontal Lobe
Temporal Lobe
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Pittsburgh
Amyloid
Cognitive Function
Protein Isoforms
Language
Regression Analysis
Retention (Psychology)
Population
Carrier

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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APOE modifies the association between Aβ load and cognition in cognitively normal older adults. / Kantarci, Kejal M; Lowe, Val; Przybelski, S. A.; Weigand, S. D.; Senjem, M. L.; Ivnik, R. J.; Preboske, G. M.; Roberts, Rosebud O; Geda, Yonas Endale; Boeve, Bradley F; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.

In: Neurology, Vol. 78, No. 4, 24.01.2012, p. 232-240.

Research output: Contribution to journalArticle

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abstract = "Objective: To determine the relationship between β-amyloid (Aβ) load as measured by [ 11C]- 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). Conclusion: 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.",
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AU - Lowe, Val

AU - Przybelski, S. A.

AU - Weigand, S. D.

AU - Senjem, M. L.

AU - Ivnik, R. J.

AU - Preboske, G. M.

AU - Roberts, Rosebud O

AU - Geda, Yonas Endale

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

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N2 - Objective: To determine the relationship between β-amyloid (Aβ) load as measured by [ 11C]- 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). Conclusion: 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.

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