Sickle Cell Trait Doesn’t Predict Cognitive Decline in African Americans, Study Finds

African Americans who inherit one sickle cell gene and one normal gene —  a condition known as sickle cell trait — are not at greater risk of cognitive decline or dementia. However, such genetic composition may influence other risk factors for cognitive impairment, researchers report.

The study with that finding, “Association of sickle cell trait with measures of cognitive function and dementia in African Americans,” was published in eNeurologicalSci.

In comparison to non-Hispanic whites, African Americans are significantly more affected by cognitive decline and dementia.

Sickle cell anemia has been associated with cognitive dysfunction, perhaps due, in part, to abnormal narrowing of the blood vessels. Increasing evidence suggests that some complications of sickle cell anemia also might affect those with sickle cell trait (SCT) — when a person inherits one abnormal hemoglobin gene and one normal gene, which is present in 8% (about 3.5 million) African Americans.

Researchers set out to determine whether inheritance of the sickle cell trait increases the risk of cognitive decline or dementia among African Americans.

To do so, they studied 2,708 African Americans enrolled in the Atherosclerosis Risk in Communities (ARIC) study. Researchers used the subjects’ genetic, cognitive and magnetic resonance imaging (MRI) data to look for an association between sickle cell trait and risk of cognitive impairment or dementia.

Regarding cognitive function, scientists evaluated global and domain-specific cognition, particularly delayed word recall, digit symbol substitution, and word fluency.

Results revealed there was no difference in risk factor profile between individuals with sickle cell trait (176) and those without it (2,532). Importantly, having an abnormal hemoglobin gene was not independently associated with a higher prevalence of global or domain-specific cognitive impairment, or with a more rapid cognitive decline. Sickle cell trait also was not associated with significant differences in cerebral volume.

“We also observed that non-diabetic participants with SCT had a 55% lower incidence of dementia compared to those without SCT. On the other hand, among participants with diabetes mellitus, those with SCT had approximately a two-fold higher risk of developing dementia compared to those without SCT, thus suggesting a possible interaction between SCT and diabetes mellitus,” the team stated.

Overall, individuals with sickle cell trait had a lower incidence of dementia compared to subjects without SCT. However, that was not significant statistically.

Studies indicate that at least one copy of the ε4 allele (meaning “variant form”) in the apolipoprotein E (APOE) gene may contribute to the incidence and prevalence of dementia and cognitive decline in both African Americans and non-Hispanic whites.

Researchers reported sickle cell trait and APOE ε4 were associated with worse performance in the digit symbol test at the beginning of the study, and a faster 20-year score decline, compared to people without the sickle cell trait.

“In conclusion, we observed that SCT was not an independent risk factor for prevalent or incident cognitive decline, but it could potentially interact with and modify other genetic risk factors for dementia and cognitive dysfunction,” investigators wrote.