Dataset Information

Effects of the APOE ?4 allele and education on cognitive function in Japanese centenarians.

ABSTRACT: Apolipoprotein E (APOE) ?4 allele and education have been reported to affect the cognitive function in young-old adults. However, the effects and interactions of the ?4 allele and education on cognitive function in very old age, particularly in centenarians, are not well known. We studied 542 Japanese centenarians. Using the data in total of 452 participants (74 men and 378 women, mean age 103.6 ± 3.2 years) who were genotyped and assessed cognitive function with the Mini-Mental States Examination (MMSE), we examined the effects and interactions of the ?4 allele and education on the MMSE score. First, we coded education as three levels: low, middle, and high based on the formal educational levels (analysis 1). Second, to clarify the modifying effect of education, we adopted a new coding for education into two levels, considering a periodical background (around 1900) of gender differences in educational attainments (analysis 2). In analysis 1, the main effects of the ?4 allele and education on the MMSE score were significant after adjusting for age. Further, there was a significant three-way interaction effect between the ?4 allele, education, and gender on the MMSE. Analysis 2 showed that the modifying effect of the ?4 allele by education was observed only in women with the ?4 allele. These findings suggest that both the APOE ?4 allele and education appear to be associated with cognitive function even in centenarians, but the interaction between the ?4 allele and education might depend on gender in this cohort.

SUBMITTER: Ishioka YL

PROVIDER: S-EPMC5266218 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Effects of the APOE ε4 allele and education on cognitive function in Japanese centenarians.

Ishioka Yoshiko Lily YL Gondo Yasuyuki Y Fuku Noriyuki N Inagaki Hiroki H Masui Yukie Y Takayama Michiyo M Abe Yukiko Y Arai Yasumichi Y Hirose Nobuyoshi N

Age (Dordrecht, Netherlands) 20160824 5-6

Apolipoprotein E (APOE) ε4 allele and education have been reported to affect the cognitive function in young-old adults. However, the effects and interactions of the ε4 allele and education on cognitive function in very old age, particularly in centenarians, are not well known. We studied 542 Japanese centenarians. Using the data in total of 452 participants (74 men and 378 women, mean age 103.6 ± 3.2 years) who were genotyped and assessed cognitive function with the Mini-Mental States Examinati ...[more]

PMID: 27558117

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Project description:BackgroundSubjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD.MethodsA total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD.ResultsCompared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers.ConclusionsIndividuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD.Trial registrationClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Project description:Background: Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of APOE-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of APOE-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment. Methods: We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, n = 167) subjects and subjects with significant memory concern (SMC, n = 96), early mild cognitive impairment (EMCI, n = 146), late cognitive impairment (LMCI, n = 138), and AD (n = 121). Subjects were further categorized according to the APOE-ε4 allele carrier status. The main effects of APOE-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, APOE-ε4 status, and cognitive performance. Results: We found that APOE-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. APOE-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, APOE-ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did. Conclusion: Our results confirmed the effect of APOE-ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.

Dataset Information

Effects of the APOE ?4 allele and education on cognitive function in Japanese centenarians.

Publications

Effects of the APOE ε4 allele and education on cognitive function in Japanese centenarians.

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