Association Between APOE Alleles and Change of Neuropsychological Tests in the Long Life Family Study

Abstract

Background: The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective: To test whether APOE genotype is associated with change of cognitive function in older adults. Methods: We used Bayesian hierarchical models to test the association between APOE alleles and change of cognitive function. Six longitudinally collected neuropsychological test scores were modelled as a function of age at enrollment, follow-up time, gender, education, field center, birth cohort indicator (≤1935, or >1935), and the number of copies of ɛ2 or ɛ4 alleles. Results: Out of 4,587 eligible participants, 2,064 were male (45.0%), and age at enrollment ranged from 25 to 110 years, with mean of 70.85 years (SD: 15.75). We detected a significant cross-sectional effect of the APOE ɛ4 allele on Logical Memory. Participants carrying at least one copy of the ɛ4 allele had lower scores in both immediate (–0.31 points, 95% CI: –0.57, –0.05) and delayed (–0.37 points, 95% CI: –0.64, –0.10) recall comparing to non-ɛ4 allele carriers. We did not detect any significant longitudinal effect of the ɛ4 allele. There was no cross-sectional or longitudinal effect of the ɛ2 allele. Conclusion: The APOE ɛ4 allele was identified as a risk factor for poorer episodic memory in older adults, while the APOE ɛ2 allele was not significantly associated with any of the cognitive test scores.

Studying the Interplay Between Apolipoprotein E and Education on Cognitive Decline in Centenarians Using Bayesian Beta Regression

“…Our findings are consistent with previous studies that showed a decline of cognitive function with older age in multiple domains (Harada et al, 2013), and the negative effect of APOE e4 on cognitive decline in centenarians (Arosio et al, 2017;Du et al, 2020). There is some evidence that, among centenarians, the e2 allele confers protection from cognitive decline (Kim et al, 2017;Sebastiani et al, 2020), in addition to increasing the chance for longevity (Sebastiani et al, 2019a) and conferring protection from aging-related diseases (Wolters et al, 2019;Kuo et al, 2020).…”

Interactive association of posttraumatic stress disorder, apolipoprotein ε4 genotype, and age on cognitive functioning

“…Although the association between APOE ε4 and long-term memory has been established, [14][15][16][17][18] the extent to which APOE ε4 may impact other domains of cognitive functioning is commonly studied. Some studies indicate that APOE ε4 carriers exhibit deficits in psychomotor speed, 19,20 attention, 21,22 working memory, [21][22][23] and learning 16,[24][25][26] compared to non-carriers. However, some studies did not observe a significant effect of APOE ε4 on psychomotor speed and attention.…”

Bayesian Variable Selection Utilizing Posterior Probability Credible Intervals

“…It yields results with parsimonious parameters with practical meaning and can achieve computational efficiency. In addition to the application example in this paper, we have also implemented this proposed algorithm in analyzing the association between familial longevity and cognitive decline, and the association between APOE allele and cognitive decline in the Long Life Family Study (LLFS) Andersen et al 2020; Du et al (2020). Method CI DIC CI DIC CI DIC CI DIC CI DIC CI DIC CI DIC CI DIC Correct Model 100 100 100 3 100 100 99 9 100 100 100 25 74 87 100 37 1 Mismatch 0 0 0 30 0 0 0 32 0 0 0 36 26 13 0 43 2 Mismatch 0 0 0 37 0 0 1 34 0 0 0 27 0 0 0 18…”