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APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND.

ABSTRACT: OBJECTIVE:Dementia is a debilitating illness with a disproportionate burden in patients with type 2 diabetes (T2D). Among the contributors, genetic variation at the apolipoprotein E locus (APOE) is posited to convey a strong effect. This study compared and contrasted the association of APOE with cognitive performance and cerebral structure in the setting of T2D. RESEARCH DESIGN AND METHODS:European Americans from the Diabetes Heart Study (DHS) MIND (n = 754) and African Americans from the African American (AA)-DHS MIND (n = 517) were examined. The cognitive battery assessed executive function, memory, and global cognition, and brain MRI was performed. RESULTS:In European Americans and African Americans, the APOE E4 risk haplotype group was associated with poorer performance on the modified Mini-Mental Status Examination (P < 0.017), a measure of global cognition. In contrast to the literature, the APOE E2 haplotype group, which was overrepresented in these participants with T2D, was associated with poorer Rey Auditory Verbal Learning Test performance (P < 0.032). Nominal associations between APOE haplotype groups and MRI-determined cerebral structure were observed. CONCLUSIONS:Compared with APOE E3 carriers, E2 and E4 carriers performed worse in the cognitive domains of memory and global cognition. Identification of genetic contributors remains critical to understanding new pathways to prevent and treat dementia in the setting of T2D.

SUBMITTER: Palmer Allred ND

PROVIDER: S-EPMC5127235 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND.

Palmer Allred Nicholette D ND Raffield Laura M LM Hardy Joycelyn C JC Hsu Fang-Chi FC Divers Jasmin J Xu Jianzhao J Smith S Carrie SC Hugenschmidt Christina E CE Wagner Benjamin C BC Whitlow Christopher T CT Sink Kaycee M KM Maldjian Joseph A JA Williamson Jeff D JD Bowden Donald W DW Freedman Barry I BI

Diabetes care 20161004 12

<h4>Objective</h4>Dementia is a debilitating illness with a disproportionate burden in patients with type 2 diabetes (T2D). Among the contributors, genetic variation at the apolipoprotein E locus (APOE) is posited to convey a strong effect. This study compared and contrasted the association of APOE with cognitive performance and cerebral structure in the setting of T2D.<h4>Research design and methods</h4>European Americans from the Diabetes Heart Study (DHS) MIND (n = 754) and African Americans ...[more]

PMID: 27703028

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Project description:ImportanceCognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature.ObjectiveTo determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD.Design, setting, and participantsWe studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE ε2/ε3/ε4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene.Main outcomes and measuresNine variables derived from 7 psychometric tests.ResultsThe APOE ε4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 × 10(-6); corrected P [Pc] = 6.0 × 10(-5)), Delayed Recall (P = .001; Pc = .009), and Recognition Discrimination Index (P = .004; Pc = .04); a semantic verbal fluency test (P = .002; Pc = .02); the Letter-Number Sequencing Test (P = 1 × 10(-5); Pc = 9 × 10(-5)); and Trail Making Test B minus Trail Making Test A (P = .002; Pc = .02). In a subset of 645 patients without dementia, the APOE ε4 allele was associated with lower scores on the HVLT-R Total Recall (P = .005; Pc = .045) and the semantic verbal fluency (P = .005; Pc = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests.Conclusions and relevanceOur data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE ε4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD.

Dataset Information

APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND.

Publications

APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND.

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