Meta-analysis of cognitive ability differences by apolipoprotein e genotype in young humans.
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ABSTRACT:
SUBMITTER: Weissberger GH
PROVIDER: S-EPMC6231411 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Meta-analysis of cognitive ability differences by apolipoprotein e genotype in young humans.
Weissberger Gali H GH Nation Daniel A DA Nguyen Caroline P CP Bondi Mark W MW Han S Duke SD
Neuroscience and biobehavioral reviews 20180817
The apolipoprotein (APOE) ε4 allele has been proposed as an example of an antagonistic pleiotropy gene, conferring a beneficial effect on cognition in early life and a detrimental impact on cognition during later years. However, findings on the cognitive associations of the ε4 allele in younger persons are mixed. This PRISMA conforming study aimed to investigate APOE genotype (e4/non-e4) associations across seven cognitive domains (intelligence/achievement, attention/working memory, executive fu ...[more]
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Project description:ImportanceIt is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established.ObjectiveTo determine how sex and APOE genotype affect the risks for developing MCI and AD.Data sourcesTwenty-seven independent research studies in the Global Alzheimer's Association Interactive Network with data on nearly 58 000 participants.Study selectionNon-Hispanic white individuals with clinical diagnostic and APOE genotype data.Data extraction and synthesisHomogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks.Main outcomes and measuresAge-adjusted odds ratios (ORs) and 95% confidence intervals for developing MCI and AD were calculated for men and women across APOE genotypes.ResultsParticipants were men and women between ages 55 and 85 years. Across data sets most participants were white, and for many participants, racial/ethnic information was either not collected or not known. Men (OR, 3.09; 95% CI, 2.79-3.42) and women (OR, 3.31; CI, 3.03-3.61) with the APOE ε3/ε4 genotype from ages 55 to 85 years did not show a difference in AD risk; however, women had an increased risk compared with men between the ages of 65 and 75 years (women, OR, 4.37; 95% CI, 3.82-5.00; men, OR, 3.14; 95% CI, 2.68-3.67; P = .002). Men with APOE ε3/ε4 had an increased risk of AD compared with men with APOE ε3/ε3. The APOE ε2/ε3 genotype conferred a protective effect on women (OR, 0.51; 95% CI, 0.43-0.61) decreasing their risk of AD more (P value = .01) than men (OR, 0.71; 95% CI, 0.60-0.85). There was no difference between men with APOE ε3/ε4 (OR, 1.55; 95% CI, 1.36-1.76) and women (OR, 1.60; 95% CI, 1.43-1.81) in their risk of developing MCI between the ages of 55 and 85 years, but women had an increased risk between 55 and 70 years (women, OR, 1.43; 95% CI, 1.19-1.73; men, OR, 1.07; 95% CI, 0.87-1.30; P = .05). There were no significant differences between men and women in their risks for converting from MCI to AD between the ages of 55 and 85 years. Individuals with APOE ε4/ε4 showed increased risks vs individuals with ε3/ε4, but no significant differences between men and women with ε4/ε4 were seen.Conclusions and relevanceContrary to long-standing views, men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages.
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Project description:ObjectivesIn this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes.MethodsWe used data from the Lothian Birth Cohort 1936 (n at Waves 1-3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes.ResultsBaseline cognitive ability had small-to-moderate negative associations with depressive symptoms (β range = -0.20 to -0.17), neuroticism (β range = -0.27 to -0.23), and allostatic load (β range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (β range = -0.98 to -0.83) and depressive symptoms (β range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load.ConclusionsOur results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline.
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Project description:The human dystrobrevin binding protein 1 (DTNBP1) gene has been linked to risk for schizophrenia. Recent studies indicate that several single nucleotide polymorphisms (SNPs) in the DTNBP1 gene may also influence general cognitive ability in both schizophrenic patients and healthy control subjects. We examined the relationship between DTNBP1 SNPs and general cognitive ability in nonpsychiatric healthy samples via meta-analysis.MEDLINE search (12/31/09) yielded 11 articles examining DTNBP1 variation and general cognitive ability, of which 8 studies had data available encompassing 10 independent cohorts (total n = 7592). The phenotype was defined as either the first principal component score from multiple neuropsychological tests (Spearman's g) or full-scale IQ. Meta-analyses were conducted for nine SNPs for which cognitive data were available from at least three cohorts. For each SNP in each cohort, effect size was computed between major allele homozygotes and minor allele carriers; effect size was then pooled across studies using a random effect model.Pooled effect sizes from two of the nine SNPs (rs1018381 and rs2619522) were -.123 and -.083, ps < .01, respectively, suggesting that the minor allele carriers of these SNPs had lower cognitive ability scores than the major allele homozygotes. Results remained significant after examining heterogeneity among samples and potential publication biases. Other SNPs did not show significant effects on general cognitive ability.Genetic variation in DTNBP1 modestly influences general cognitive ability. Further studies are needed to elucidate the biological mechanisms that may account for this relationship.
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Project description:Neuroimaging research involves analyses of huge amounts of biological data that might or might not be related with cognition. This relationship is usually approached using univariate methods, and, therefore, correction methods are mandatory for reducing false positives. Nevertheless, the probability of false negatives is also increased. Multivariate frameworks have been proposed for helping to alleviate this balance. Here we apply multivariate distance matrix regression for the simultaneous analysis of biological and cognitive data, namely, structural connections among 82 brain regions and several latent factors estimating cognitive performance. We tested whether cognitive differences predict distances among individuals regarding their connectivity pattern. Beginning with 3,321 connections among regions, the 36 edges better predicted by the individuals' cognitive scores were selected. Cognitive scores were related to connectivity distances in both the full (3,321) and reduced (36) connectivity patterns. The selected edges connect regions distributed across the entire brain and the network defined by these edges supports high-order cognitive processes such as (a) (fluid) executive control, (b) (crystallized) recognition, learning, and language processing, and (c) visuospatial processing. This multivariate study suggests that one widespread, but limited number, of regions in the human brain, supports high-level cognitive ability differences. Hum Brain Mapp 38:803-816, 2017. © 2016 Wiley Periodicals, Inc.
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Project description:This study examined the impact of age and apolipoprotein E (APOE) genotype on the rate of cognitive decline in nondemented elderly participants in a simulated Alzheimer's disease (AD) primary prevention treatment trial carried out by the Alzheimer's Disease Cooperative Study.Cognitive tests were administered at baseline and at four subsequent annual evaluations to 417 nondemented participants (172 men, 245 women) between the ages of 74 and 93 (M = 79.13 ± 3.34). APOE genotyping was available for 286 of the participants.Four-year decline was evident on measures of orientation, memory, executive function, and language. Faster decline was evident in APOE ?4+ (a genetic risk factor for AD; n = 73) than in ?4- participants (n = 213), even after controlling for education, gender, ethnicity, and baseline functional and cognitive abilities. This discrepancy increased with age, indicating an Age × Genotype interaction.These results are consistent with population-based studies, and extend the findings to a carefully screened sample that meets inclusion and exclusion criteria for an AD primary prevention trial. The interaction between age and APOE genotype on rate of decline suggests that preclinical disease may be overrepresented in older ?4+ individuals. Thus, APOE genotype and age should be considered in the design of AD primary prevention treatment trials.
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Project description:Purpose/objectivesTo examine the role of apolipoprotein E (APOE) genotype in the cognitive function of postmenopausal women with early-stage breast cancer prior to initiation of adjuvant therapy and over time with treatment.DesignLongitudinal, genetic association study.SettingUrban university cancer center.SampleThree cohorts of postmenopausal women: 37 women with breast cancer receiving chemotherapy and anastrozole, 41 women with breast cancer receiving anastrozole alone, and 50 healthy women.MethodsCognitive function was evaluated three times during a 12-month period using a comprehensive neuropsychological test battery. Participants were genotyped and classified based on the presence or absence of at least one APOE e4 allele. Multiple linear regression was used to determine if APOE genotype accounted for observed variability in cognitive function data.Main research variablesAPOE genotype, breast cancer treatment, and cognitive function.FindingsPerformance or changes in performance on tasks of executive function, attention, verbal learning and memory, and visual learning and memory were found to be influenced by APOE genotype and/or interactions between APOE genotype and study cohort.ConclusionsThe results indicate that cognitive function in postmenopausal women with breast cancer is modified by APOE genotype and the combination of APOE genotype and treatment.Implications for nursingAPOE genotype, along with other biomarkers, may be used in the future to assist nurses in identifying women with breast cancer most at risk for cognitive decline.
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Project description:BackgroundPhthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex differences in cognitive performance are wider with higher phthalate concentrations.MethodsData were collected from PubMed (1998-2022), PROQUEST (1997-2022), and SpringerLink (1995-2022). The study followed the PRISMA process. The included articles were followed by PECO framework. The GRADE applied to assess the certainty of evidence. Of 2422 articles obtained, nine were selected using inclusion criteria. The random-effects model was used to estimate the pooled effects.ResultsOur meta-regression indicated a significant difference between sex differences with age at phthalate concentration assessment (β = -0.25; 95% CI = -0.47, -0.03) and MEHP concentration (β = -0.20; 95% CI = -0.37, -0.03).ConclusionsThe limitation of the current article is it only provides information on intelligence level rather than other aspects of cognitive function. Thus, the sequelae of phthalate exposure on attention and executive function are still unclear. Our analysis shows significant difference between sex differences in cognitive function scores associated with age at phthalate concentration assessment. Girls might be more resilient in cognitive function at a younger age or during lower concentrations of phthalates metabolites.ImpactThis is the first meta-analysis to evaluate the pooled estimates of sex differences in objective cognitive functions among children with phthalate exposure. The female might be a protective factor when exposed to toxic plasticizers while the concentration is low. This study captures the possible role of sex in cognitive functioning and plasticizer exposure through a meta-analysis of children's sex, cognitive scores, and plasticizer exposure.
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Project description:Searching for a neurobiological understanding of human intellectual capabilities has long occupied those very capabilities. Brain gyrification, or folding of the cortex, is as highly evolved and variable a characteristic in humans as is intelligence. Indeed, gyrification scales with brain size, and relationships between brain size and intelligence have been demonstrated in humans [1-3]. However, gyrification shows a large degree of variability that is independent from brain size [4-6], suggesting that the former may independently contribute to cognitive abilities and thus supporting a direct investigation of this parameter in the context of intelligence. Moreover, uncovering the regional pattern of such an association could offer insights into evolutionary and neural mechanisms. We tested for this brain-behavior relationship in two separate, independently collected, large cohorts-440 healthy adults and 662 healthy children-using high-resolution structural neuroimaging and comprehensive neuropsychometric batteries. In both samples, general cognitive ability was significantly associated (pFDR < 0.01) with increasing gyrification in a network of neocortical regions, including large portions of the prefrontal cortex, inferior parietal lobule, and temporoparietal junction, as well as the insula, cingulate cortex, and fusiform gyrus, a regional distribution that was nearly identical in both samples (Dice similarity coefficient = 0.80). This neuroanatomical pattern is consistent with an existing, well-known proposal, the Parieto-Frontal Integration Theory of intelligence [7], and is also consistent with research in comparative evolutionary biology showing rapid neocortical expansion of these regions in humans relative to other species. These data provide a framework for understanding the neurobiology of human cognitive abilities and suggest a potential neurocellular association.
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