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Observational Study
. 2021;83(2):853-860.
doi: 10.3233/JAD-201205.

APOE E2/E2 Is Associated with Slower Rate of Cognitive Decline with Age

Benjamin Sweigart  1 , Stacy L Andersen  2 , Anastasia Gurinovich  3 , Stephanie Cosentino  4   5 , Nicole Schupf  4   5 , Thomas T Perls  2 , Paola Sebastiani  3
Affiliations
Observational Study

APOE E2/E2 Is Associated with Slower Rate of Cognitive Decline with Age

Benjamin Sweigart et al. J Alzheimers Dis. 2021.

Abstract

Background: The E4 allele of the APOE gene is known to be associated with cognitive impairment. However, a limited number of studies have examined the association between the E2 allele and longitudinal changes of cognitive function.

Objective: To determine whether rates of cognitive change differ in carriers of the APOE E2 allele compared to other genotypes.

Methods: We conducted a secondary analysis of data from two ongoing longitudinal cohort studies, the Long Life Family Study (LLFS) and New England Centenarian Study (NECS). We included participants who had APOE genotyping data, data from longitudinal administrations of the Telephone Interview for Cognitive Status (TICS), and age, sex, and education available. We assessed whether cognitive change as measured by rate of decline in TICS score differed among people with different APOE genotypes. We used a hierarchical mixed effect model with APOE genotypes, their interactions with age, and potential confounders.

Results: After adjusting for sex and education, in carriers of the common E3/E3 genotype, TICS score decreased by 0.15 points per year of age. In those with the E2/E2 genotype, TICS score decreased by 0.05 points per year of age, a significantly slower rate of decline (p = 0.017). We observed no protective effect of the E2/E3 genotype on cognitive decline.

Conclusion: These results suggest a protective effect of the E2/E2 genotype on a measure of global cognitive function.

Keywords: Apolipoproteins E; cognitive aging; cognitive dysfunction; genetics.

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Conflict of interest statement

CONFLICT OF INTEREST/DISCLOSURE STATEMENT: The authors have no conflict of interest to report.

Figures

Figure 1
Figure 1
Observed and predicted TICS scores by age and genotype. Connected points represent observed TICS scores for an individual. The solid line shows the predicted TICS score based on a model using age, genotype, and an age–genotype interaction term as predictors.
See this image and copyright information in PMC

References

    1. Floris M, Olla S, Schlessinger D, Cucca F (2018) Genetic-Driven Druggable Target Identification and Validation. Trends Genet 34, 558–570. - PMC - PubMed
    1. Belloy ME, Napolioni V, Greicius MD (2019) A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward. Neuron 101, 820–838. - PMC - PubMed
    1. Yamazaki Y, Zhao N, Caulfield TR, Liu C-C, Bu G (2019) Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nature Reviews Neurology 15, 501–518. - PMC - PubMed
    1. Suri S, Heise V, Trachtenberg AJ, Mackay CE (2013) The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2. Neuroscience & Biobehavioral Reviews 37, 2878–2886. - PubMed
    1. Sebastiani P, Gurinovich A, Nygaard M, Sasaki T, Sweigart B, Bae H, Andersen SL, Villa F, Atzmon G, Christensen K, Arai Y, Barzilai N, Puca A, Christiansen L, Hirose N, Perls TT (2019) APOE Alleles and Extreme Human Longevity. J Gerontol A Biol Sci Med Sci 74, 44–51. - PMC - PubMed

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