Is Sickle Cell Trait Associated With Cognitive Impairment in African Americans?

Analysis of findings from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study found no association between sickle cell trait and cognitive impairment.

An analysis of results from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study shows that sickle cell trait (SCT) is not associated with cognitive impairment in a cohort of African Americans, according to findings reported in EClinicalMedicine.

Researchers hypothesized that adults at least 45 years old who carry SCT and have normal cognitive function would be more likely than SCT-free individuals to develop cognitive impairment over several years of follow-up, because there is a link between cognitive decline and those who have developed sickle cell anemia. “Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait,” researchers said in the abstract.

REGARDS was a longitudinal observational study that investigated racial and geographical variation in acquired cognitive impairment and incidence of stroke in the contiguous United States. Participants were randomly selected by mail, enrolled by telephone, and were visited in their homes between 2003 and 2007. REGARDS enrolled a total of 30,239 black and white Americans who were followed every 6 months.

REGARDS conducted global cognitive function testing using the Six-item Screener (SIS), a validated telephone-administered instrument for global cognitive function that assessed 3-item recall and orientation to year, month, and day of the week, which resulted in scores from 0 to 6 depending on correctly answered questions. A score that was less than or equal to 4 was considered positive for cognitive impairment. The SIS was first administered at baseline and then annually to all participants. The outcome of incident cognitive impairment was defined at the most recent assessment as of April 1, 2015, when the analysis data set was closed.

Participants completed a 3-test battery every 2 years that evaluated measures of learning, memory, and executive function. Validated tests assessed word list learning, delayed recall, semantic fluency, and phonemic fluency.

Black participants with the STC genotype who had available data at baseline and at least 1 follow-up SIS were included in the analysis. Participants who were white, had hemoglobin SS or SC genotype, developed incident stroke, or had baseline cognitive impairment were excluded.

Of the 7743 participants that were followed for a median period of 7.1 years, 85 of 583, or 14.6%, with SCT developed incident cognitive impairment, compared to 902 of 7160, or 12.6%, without SCT. When univariate analysis was conducted, the odds ratio of incident cognitive impairment was found to be 1.18 for those with SCT compared to those without it. The odds ratio was not impacted by adjustment.

Researchers determined that SCT was not associated with incidence of cognitive impairment or with changes over time in test scores included in the 3-test battery.

“In this large contemporary cohort of black Americans, there were no associations of SCT with incidence of cognitive impairment or with changes over time in test scores included in a 3-test battery assessing learning, memory, and semantic and phonemic fluency. These findings suggest that, unlike findings to date in SCA, biological consequences of SCT do not appear to cause cognitive dysfunction,” researchers concluded.

Researchers suggested a detailed study that examines cognitive impairment in a younger cohort of adults or in children should be conducted to confirm their findings.


Cahill CR, Leach, JM, McClure LA, et al. Sickle cell trait and risk of cognitive impairment in African-Americans: the REGARDS cohort [published online May 23, 2019]. EClinicalMedicine. 2019. doi:

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