Dataset Information

Apolipoprotein ?4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

ABSTRACT: Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ?4 allele of apolipoprotein E (APOE ?4) is a well-established risk factor for Alzheimer's disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ?4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ?4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ?4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ?4 and being Chinese. The APOE ?4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (Puncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (Puncorrected<0.01), all regions that are associated with neurodegeneration in AD. After correction for multiple testing, the left cuneus remained significantly associated with the interaction effect (PFWE = 0.05). Our study suggests there is a differential effect of APOE ?4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ?4 effects on the brain in diverse populations.

SUBMITTER: Yokoyama JS

PROVIDER: S-EPMC4349764 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

Yokoyama Jennifer S JS Lee Allen K L AK Takada Leonel T LT Busovaca Edgar E Bonham Luke W LW Chao Steven Z SZ Tse Marian M He Jing J Schwarz Christopher G CG Carmichael Owen T OT Matthews Brandy R BR Karydas Anna A Weiner Michael W MW Coppola Giovanni G DeCarli Charles S CS Miller Bruce L BL Rosen Howard J HJ

PloS one 20150304 3

Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer's disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia ...[more]

PMID: 25738563

Similar Datasets

Project description:ImportanceApolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects.ObjectiveUsing APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE ε4 carriers.Design, setting, and participantsParticipants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE ε4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination.Main outcomes and measuresWe stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE ε4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE ε4 carriers.ResultsAmong white APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE ε4 carriers. Among black APOE ε4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience.Conclusions and relevanceAlthough APOE ε4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE ε4 carriers.

Dataset Information

Apolipoprotein ?4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

Publications

Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets