Association of sickle cell trait with measures of cognitive function and dementia in African Americans

• Type of Material: Article
• Authors: Nemin Chen, University of Pittsburgh; Christina Caruso, Emory University; Alvaro Alonso, Emory University; Vimal K. Derebail, University of North Carolina; Abhijit V. Kshirsagar, University of North Carolina; A. Richey Sharrett, Johns Hopkins University; Nigel S. Key, University of North Carolina; Rebecca F. Gottesman, Johns Hopkins University; Megan L. Grove, University of Texas Houston; Jan Bressler, University of Texas Houston; Eric Boerwinkle, University of Texas Houston; B. Gwen Windham, University of Mississippi; Thomas H. Mosley, Jr., University of Mississippi; Hyacinth Idu Hyacinth, Emory University
• Language: English
• Date: 2019-09-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ensci.2019.100201
• Title of Journal or Parent Work: eNeurologicalSci
• ISSN: 2405-6502
• Volume: 16
• Start Page: 100201
• End Page: 100201
• Grant/Funding Information: Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I), R01HL087641, R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C.; Additional support for this work was provided by grants to V.K.D. from NIH/NHLBI (5K12HL087097).; Neurocognitive data is collected by U01 HL096812, HL096814, HL096899, HL096902, HL096917.; MRI examinations funded by R01-HL70825.; H.I.H. is currently supported by grants from NIH/NHLBI (U01HL117721, R01HL138423).
• Keywords: Health disparity; Genetic epidemiology; Sickle cell trait; Cerebrovascular disease; Cognitive impairment
• Research Categories: Biology, Neuroscience; Biology, Genetics; Health Sciences, Epidemiology

Abstract

Objective: The incidence and prevalence of cognitive decline and dementia are significantly higher among African Americans compared with non-Hispanic Whites. The aim of this study was to determine whether inheritance of the sickle cell trait (SCT) i.e. heterozygosity for the sickle cell mutation increases the risk of cognitive decline or dementia Among African Americans. Methods: We studied African American participants enrolled in the Atherosclerosis Risk in Communities study. SCT genotype at baseline and outcome data from cognitive assessments at visits 2, 4 and 5, and an MRI performed at visit 5 were analyzed for the association between SCT and risk of cognitive impairment and/or dementia. Results: There was no significant difference in risk factors profile between participants with SCT (N = 176) and those without SCT (N = 2532). SCT was not independently associated with a higher prevalence of global or domain-specific cognitive impairment at baseline or with more rapid cognitive decline. Participants with SCT had slightly lower incidence of dementia (HR = 0.63 [0.38, 1.05]). On the other hand, SCT seems to interact with the apolipoprotein E ε4 risk allele resulting in poor performance on digit symbol substitution test at baseline (z-score = −0.08, Pinteraction = 0.05) and over time (z-score = −0.12, Pinteraction = 0.04); and with diabetes mellitus leading to a moderately increased risk of dementia (HR = 2.06 [0.89, 4.78], Pinteraction = 0.01). Conclusions: SCT was not an independent risk factor for prevalence or incidence of cognitive decline or dementia, although it may interact with and modify other putative risk factors for cognitive decline and dementia.