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Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ?4 allele.

ABSTRACT: We have previously demonstrated cross-sectional differences in magnetic resonance imaging (MRI) measurements of white matter myelin and gray matter in infants with or without the apolipoprotein ?4 allele, a major genetic risk factor for late-onset Alzheimer's disease (AD). In this study, we sought to compare longitudinal MRI white matter myelin and cognitive-behavioral changes in infants and young children with and without this allele. Serial MRI and cognitive tests were obtained on 223 infants and young children, including 74 ?4 carriers and 149 non-carriers, 2-68 months of age, matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated brain mapping algorithms and non-linear mixed models were used to characterize and compare trajectories of white matter myelin and cognitive-behavioral test scores. The APOE ?4 carriers had statistically significant differences in white matter myelin development, in the uncinate fasciculus, temporal lobe, internal capsule and occipital lobe. Additionally, ?4 carriers had a slightly greater rate of development in early learning composite a surrogate measure of IQ representative of expressive language, receptive language, fine motor, and visual skills, but displayed slightly lower non verbal development quotient scores a composite measure of fine motor and visual skills across the entire age range. This study supports the possibility that ?4 carriers have slightly altered rates of white matter and cognitive development in childhood. It continues to raise questions about the role of APOE in human brain development and the relevance of these developmental differences to the predisposition to AD.

SUBMITTER: Remer J

PROVIDER: S-EPMC7779366 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ε4 allele.

Remer Justin J Dean Douglas C DC Chen Kewei K Reiman Rebecca A RA Huentelman Matthew J MJ Reiman Eric M EM Deoni Sean C L SCL

NeuroImage 20200818

We have previously demonstrated cross-sectional differences in magnetic resonance imaging (MRI) measurements of white matter myelin and gray matter in infants with or without the apolipoprotein ε4 allele, a major genetic risk factor for late-onset Alzheimer's disease (AD). In this study, we sought to compare longitudinal MRI white matter myelin and cognitive-behavioral changes in infants and young children with and without this allele. Serial MRI and cognitive tests were obtained on 223 infants ...[more]

PMID: 32822813

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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

Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ?4 allele.

Publications

Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ε4 allele.

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