Dataset Information

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

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.

SUBMITTER: Sweigart B

PROVIDER: S-EPMC8896199 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Sweigart Benjamin B Andersen Stacy L SL Gurinovich Anastasia A Cosentino Stephanie S Schupf Nicole N Perls Thomas T TT Sebastiani Paola P

Journal of Alzheimer's disease : JAD 20210101 2

<h4>Background</h4>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.<h4>Objective</h4>To determine whether rates of cognitive change differ in carriers of the APOE E2 allele compared to other genotypes.<h4>Methods</h4>We conducted a secondary analysis of data from two ongoing longitudinal cohort studies, the Long Life Family St ...[more]

PMID: 34366332

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Project description:The genetic protective factors for cognitive decline in aging remain unknown. Predicting an individual's rate of cognitive decline-or with better cognitive resilience-using genetics will allow personalized intervention for cognitive enhancement and the optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores (GPS) of cognitive capacity as the genomic indicators for variations of human intelligence, we analyzed the 18-year records of cognitive and behavioral data of 8511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), specifically focusing on the cognitive assessments that were repeatedly administered to the participants with their average ages of 64.5 and 71.5. We identified a significant interaction effect between age and cognitive capacity GPS, which indicated that a higher cognitive capacity GPS significantly correlated with a slower cognitive decline in the domain of immediate memory recall (β = 1.86 × 10-1, p-value = 1.79 × 10-3). The additional phenome-wide analyses identified several associations between cognitive capacity GPSs and cognitive/behavioral phenotypes, such as similarities task (β = 1.36, 95% CI = (1.22, 1.51), p-value = 3.59 × 10-74), number series task (β = 0.94, 95% CI = (0.85, 1.04), p-value = 2.55 × 10-78), IQ scores (β = 1.42, 95% CI = (1.32, 1.51), p-value = 7.74 × 10-179), high school classrank (β = 1.86, 95% CI = (1.69, 2.02), p-value = 3.07 × 10-101), Openness from the BIG 5 personality factor (p-value = 2.19 × 10-14, β = 0.57, 95% CI = (0.42, 0.71)), and leisure activity of reading books (β = 0.50, 95% CI = (0.40, 0.60), p-value = 2.03 × 10-21), attending cultural events, such as concerts, plays, or museums (β = 0.60, 95% CI = (0.49, 0.72), p-value = 2.06 × 10-23), and watching TV (β = -0.48, 95% CI = (-0.59, -0.37), p-value = 4.16 × 10-18). As the first phenome-wide analysis of cognitive and behavioral phenotypes, this study presents the novel genetic protective effects of cognitive ability on the decline of memory recall in an aging population.

Project description:ObjectiveAn Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ε4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE.MethodsParticipants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ε4 alleles and either a high or low g-score: APOE ε4-/low g-score; APOE ε4-/high g-score; APOE ε4+/low g-score; and APOE ε4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE.ResultsIndividuals in the APOE ε4+/high g-score group exhibited the greatest cognitive decline over time (p<.0001). This risk appeared to be greater than the sum of the effects of either high g-score or APOE ε4 alone. When gene interactions were individually tested with APOE, a statistically significant interaction with CD33 was discovered (p = 0.04) although the interaction was no longer significant when adjusted for multiple comparisons.ConclusionsIndividuals with multiple AD risk genes in addition to having one or more APOE ε4 alleles are at greater risk of cognitive decline than individuals with either APOE ε4 or a high genetic risk score. Among those with one or more APOE ε4 alleles, having one or more copies of the CD33 C (risk) allele may further increase the risk of cognitive decline.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

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