Association Of Ε4 Research Articles

Effects of ApoE in the Panama aging research initiative: A community‐dwelling older adults’ cohort in Panama

AbstractBackgroundThe Panama Aging Research Initiative (PARI) is a longitudinal study of more than 800 adults aged 60 years and older. The objective of this analysis consists of identifying the effects of Apolipoprotein E (ApoE) gene as a risk factor for sporadic Alzheimer’s disease (AD), with elevated risk for ε4‐carriers and reduced risk for ε2‐carriers.MethodOur ongoing community‐based cohort (n = 400) has undergone clinical interviews, neuropsychological testing, and assessments of frailty at two time points (14‐29 months apart). Fasting blood draws were obtained for measurements of genetic and blood‐based biological markers. DNA was extracted from whole blood and (ApoE) genotyping (n = 330) was conducted according to standardized PCR procedures. We will examine whether ε2 and ε4 are associated with differential rates of normal cognitive aging, and whether associations of ε4 with cognitive decline are modified by sex, education or other health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and frailty.ResultOur study evaluate whether ApoE ε2, ε3 and ε4 allele frequency is a significant factor associated with cognition and daily function in elderly individuals. Specifically, we focus on evaluating the frequency of ApoE ε4 expression as a risk for cognitive impairment. Together these results contribute to our understanding of the risk factors of cognitive outcomes among Hispanic populations outside the US.ConclusionLittle is known about the factors associated to cognitive health at old age in Central American populations. Genetic biomarkers could be used as a tool for diagnostic testing. It is expected that ApoE‐ε4 polymorphism will correlate with cognitive deficit among the elderly population and those at risk for cognitive impairment.

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

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). 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. 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 noncarriers. The influence of ε4 on cognitive aging did not differ by sex, nor was it modified by smoking or exercise. 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. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Apolipoprotein E genotype impact on memory and attention in older persons: the moderating role of personality phenotype.

To determine if phenotypic personality traits modify the association of Apolipoprotein E (APOE) genotypes with different domains of cognitive function. Cross-sectional. 172 non-demented older adults were administered the NEO-Five Factor Inventory (NEO-FFI), a battery of neuropsychological tests assessing memory, attention, executive function, language, and visuospatial ability, and underwent APOE genotyping. Multivariate (multiple-dependent variable) regression models predicting cognitive domains tested APOE interactions with personality traits, adjusting for age, sex, and education. The APOE ε4 allele showed small to modest main effects on memory and executive function (1/3 SD deficits for carriers, p<.05), with ε2 status evidencing minimal and non-significant benefit. Neuroticism interacted with both ε2 and ε4 alleles in associations with attention scores (p=.001), with ε2 benefits and ε4 deficits being marked at high Neuroticism (Mean [M] covariate-adjusted Z-score=.39 for ε2, -.47 for ε4). The association of ε4 with memory was moderated by Conscientiousness (p<.001), such that ε4 memory deficits were apparent at low Conscientiousness (M=-.56), but absent at high levels of Conscientiousness. Weaker patterns (p<.05) also suggested ε4-related detriments in executive function only at lower Conscientiousness, and ε2 memory benefits only at higher Openness. Conscientiousness and Neuroticism moderate APOE associations with memory and executive function. As such, they may be useful phenotypic markers in refining the prognostic significance of this polymorphism. Effect-modifying personality traits also provide clues about behavioral and psychological factors that influence the cognitive impact of APOE. Copyright © 2017 John Wiley & Sons, Ltd.

Associations of APOE ε4 With Health and Financial Literacy Among Community-Based Older Adults Without Dementia.

Older adults often exhibit low health and financial literacy, but the reasons why remain unclear. One possibility is that those older adults at high risk for developing dementia demonstrate low literacy even in the absence of marked cognitive impairment. We therefore examined associations of health and financial literacy with the APOE ε4 allele, the chief genetic risk factor for Alzheimer's disease, among older adults without dementia. Participants were 487 older adults without dementia enrolled in the Rush Memory and Aging Project (mean age = 83, mean years of education = 15, 77% female, 91% non-Hispanic White). Participants underwent APOE genotyping and assessments of cognition, health literacy, and financial literacy. Health and financial literacy scores were also averaged into a total literacy score. ε4 was associated with lower total and health literacy, with a trend toward an association with lower financial literacy, after adjustment for age, sex, and education. Associations of ε4 with lower total and health literacy persisted after further adjustment for global cognitive function and 5 specific cognitive domains. ε4 affects literacy even in the absence of clinical dementia and does so relatively independent of performance on traditional cognitive tests.

APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis

ObjectivesCerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the ε4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both...

Genetic associations with brain microbleeds

We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of >100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I² and χ² statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. Only the APOE ε2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the ε3/ε3 genotype, carriers of the ε4 allele (ε4+) were statistically significantly more likely to have BMBs in any location (ε4+ vs ε3/ε3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (ε4+ vs ε3/ε3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of ε4+ genotypes with strictly lobar BMBs was reasonably robust to potential publication and reporting biases. Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy.

The Apolipoprotein E ε4 Allele Is Unlikely to Be a Major Risk Factor of Age-Related Macular Degeneration in Chinese

Apolipoprotein E (ApoE) is a major transporter of lipids and cholesterol in the nervous system. Age-related macular degeneration (ARMD), characterized by drusen containing lipids, was reported to show a lower frequency of the ApoE ε4 allele than control subjects. We sought to examine the association of this polymorphism with ARMD in Hong Kong Chinese. Among 98 ARMD subjects, the frequency of ε4 carriers showed a trend toward a decrease compared to controls, but it was not significant (11.2 vs. 15.0%, p < 0.52). The association of ε4 with an apparent reduced risk of ARMD was reported previously in the exudative form of the disease, however among 39 exudative ARMD patients there was also no significant difference in ε4 frequency (12.8%, p < 0.93). The lack of a statistically significant effect of ε4 may be due to the lower frequency of ε4 in Chinese than Europeans. Thus we cannot exclude a possible effect of this allele on ARMD risk, but we can conclude that this allele is likely not a major factor influencing ARMD risk in the Chinese.