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Author Notes:

Corresponding author at: Aflac Cancer and Blood Disorder Center, Emory Children's Center, Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, United States of America. hhyacinth@emory.edu

AA and HIH conceived and designed the study.

NC and AA performed data analysis guided by HIH.

NC and CC wrote the initial manuscript draft.

VKD, AK, RS, NK, RFG, MLG, JB, EB, BGW, THM and HIH provided critical reviews of subsequent iterations of the manuscript.

All authors listed contributed enough to merit authorship.

The authors thank the staff and participants of the ARIC study for their important contributions.

The authors have no relevant financial conflict to disclose.


Research Funding:

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.

Neurocognitive data is collected by U01 HL096812, HL096814, HL096899, HL096902, HL096917.

MRI examinations funded by R01-HL70825.

Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.

Additional support for this work was provided by grants to V.K.D. from NIH/NHLBI (5K12HL087097).

H.I.H. is currently supported by grants from NIH/NHLBI (U01HL117721, R01HL138423).


  • Cerebrovascular disease
  • Cognitive impairment
  • Genetic epidemiology
  • Health disparity
  • Sickle cell trait

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

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Journal Title:



Volume 16


, Pages 100201-100201

Type of Work:

Article | Final Publisher PDF


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.

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© 2019 The Authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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