Effects of APOE on cognitive aging in community-dwelling older adults.

Abstract

Objective: The apolipoprotein E (APOE) gene is an established risk factor for sporadic Alzheimer’s disease, with elevated risk for ε4-carriers and reduced risk for ε2-carriers. However, it is unclear whether APOE modifies risk for cognitive decline in normal aging. The objective of this study was to determine whether ε2 and ε4 are associated with rates of normal cognitive aging, and whether associations of ε4 with cognitive decline are modified by sex, education or health behaviors (exercise, alcohol consumption, smoking). Method: A community-based sample of 1,393 older adults were genotyped for APOE and underwent cognitive assessment up to seven times over a maximum of period of 27 years. Results: ε2-carriers showed slower executive function decline with age relative to ε3 homozygotes or ε4-carriers, whereas ε4-carriers demonstrated more rapid executive function and verbal fluency decline. Accelerated executive function decline was particularly pronounced in ε4-carriers with lower education. After excluding individuals with cognitive impairment, faster executive function decline was still apparent in ε4-carriers, and the effect of ε4 on episodic memory interacted with alcohol consumption, such that only ε4-carriers who did not drink showed more rapid memory decline than ε4 non-carriers. The influence of ε4 on cognitive aging did not differ by sex, nor was it modified by smoking or exercise. Conclusions: These findings indicate that the ε2 and ε4 alleles have differential effects on cognitive aging, and that negative effects of ε4 may be partly mitigated by behavioral choices.

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

“…Behaviorally, we found that both -APOE4 and +APOE4 individuals performed well on neuropsychological tests as well as our episodic memory task, with greater MoCA scores in +APOE4 individuals. These results largely align with previous studies showing no significant behavioral differences in cognitive performance on the basis of APOE4 status in younger (Taylor et al, 2017) and healthy older adults of similar demographic background (Reas et al, 2019), as well as our previous work using a similar episodic memory task in middle-aged adults at risk of AD (Rajah et al, 2017). However, given the high sensitivity of the MoCA for detecting mild cognitive impairment (Pinto et al, 2019), lower MoCA performance among -APOE4 participants may support theories suggesting that carrying an APOE4 allele may paradoxically benefit cognitive function in early and midlife (Evans et al, 2014).…”

“…Moreover, lifestyle choices (e.g., higher education level, moderate alcohol consumption) may mitigate APOE4 effects and contribute to discrepant reports of its influence on cognitive aging (Reas et al, 2019). Although an investigation of lifestyle factors was beyond the scope of this study, high education among both APOE4 groups, coupled with our participants' eagerness to engage in stimulating activities such as PREVENT-AD, may at least partly explain our lack of observed group differences in behavior and task-related fMRI.…”

Association between Thyroid Hormones, Apolipoprotein E, and Cognitive Function among Cognitively-Normal Elderly Dwellers

“…This could lead to discrepant results between VFT and other tests. This could be supported by a recent study demonstrating that the ε4 allele carriers who were cognitively intact recorded significant decline in executive function, while no statistical association between APOE and verbal fluency was found [ 8 ]. Accordingly, our result can help broaden our knowledge about the interaction between the APOE ε4 allele and TSH significantly affecting SM or even executive components embedded in VFT at least across CN elderly population.…”

“…These areas have been well-established to be involved in memory performance. As implied in this connection, a recent study reported older participants carrying the APOE ε4 allele demonstrated poor performance in VFT, while this correlation did not exist after the exclusion of cognitively-impaired participants [ 8 ]. Other studies illustrated that APOE ε4 allele influenced an episodic memory test as compared with a semantic counterpart [ 34 ].…”

“…Alteration of the thyroid hormonal state has been reported to constitute a risk factor for developing dementia at a later stage of life [ 5 , 6 ]. The Apolipoprotein E (APOE) gene has also been hypothesized to be a risk factor for late-onset AD [ 7 , 8 ]. As a result, research has been conducted to elucidate how these risk factors are correlated with cognitive function, since cognitive impairment was reported to be one of initial symptoms of AD [ 9 ].…”