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

Nemin Chen; Christina Caruso; Alvaro Alonso; Vimal K Derebail; Abhijit V Kshirsagar; A Richey Sharrett; Nigel S Key; Rebecca F Gottesman; Megan L Grove; Jan Bressler; Eric Boerwinkle; B Gwen Windham; Thomas H Mosley Jr; Hyacinth I Hyacinth

doi:10.1016/j.ensci.2019.100201

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

eNeurologicalSci. 2019 Jul 22:16:100201. doi: 10.1016/j.ensci.2019.100201. eCollection 2019 Sep.

Authors

Affiliations

¹ Department of Epidemiology, University of Pittsburg, Pittsburg, PA, United States of America.
² Aflac Cancer and Blood Disorder Center of Children's Healthcare of Atlanta, Emory Department of Pediatrics, Atlanta, GA, United States of America.
³ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States of America.
⁴ UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
⁵ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
⁶ University of North Carolina, Department of Medicine, Chapel Hill, NC, United States of America.
⁷ Department of Neurology, Johns Hopkins University, Baltimore, MD, United States of America.
⁸ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
⁹ Human Genome Sequencing Center at Baylor College of Medicine, Houston, TX, United States of America.
¹⁰ University of Mississippi Medical Center, Department of Medicine/Geriatrics, Jackson, MS, United States of America.
¹¹ MIND Center, University of Mississippi Medical Center, Jackson, MS, United States of America.

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, P_interaction = 0.05) and over time (z-score = -0.12, P_interaction = 0.04); and with diabetes mellitus leading to a moderately increased risk of dementia (HR = 2.06 [0.89, 4.78], P_interaction = 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.

Keywords: Cerebrovascular disease; Cognitive impairment; Genetic epidemiology; Health disparity; Sickle cell trait.

Abstract

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