Antiretroviral Therapy and APOE4 Genotype, in Combination, May Expedite Cognitive Decline for HIV Positive Men

Men over the age of 50 who have human immunodeficiency virus (HIV) and who are adherent to an antiretroviral therapy (ART) regimen are at risk for cognitive decline, according to the results of a recent study. Shibani Mukerji, MD, PhD, of the Department of Neurology at Massachusetts General Hospital in Boston, and colleagues, conducted the study, which was published in the journal Clinical Infectious Diseases on August 11, 2016.

Thanks to the success of ART, patients with HIV are living longer, and therefore face different risks. One of those risks is dyslipidemia, which is, in turn, a risk factor for dementia. Apolipoprotein E (APOE) transports cholesterol within the central nervous system, and allele 4 (APOE4) is also the “most important genetic risk factor for Alzheimer’s disease, and a risk factor for age-related cognitive decline in the general population,” according to the authors.

Researchers have not yet discovered a relationship between HIV-1 associated neurocognitive disorders (HAND) and APOE4. In an effort to understand any possible link, the authors of the present study “examined the effect of lipid profiles and APOE4 allele on cognitive decline in a cohort of ART-adherent HIV positive and HIV negative men aged 50-65 years,” they said. They further modeled the interaction between high cholesterol levels and statins or the APOE4 genotype to estimate how the combined effect would change the rate of cognitive decline.

They found that higher cholesterol levels in both the ART adherent group and the control group led to a faster rate of decline, and that those in the ART adherent group had an even more accelerated rate of decline than those in the control group.

Additionally, they said the APOE4 genotype “was associated with accelerated cognitive decline” in members of the adherent group older than 50 years, which they said is “approximately a decade earlier than reported” for the APOE4 carriers in the control group. They say this suggests ART treatment in those with the APOE4 genotype is “a significant risk factor for earlier onset of cognitive decline,” they said.

The use of statins appeared to attenuate the level of cholesterol, and by extension, the rate of cognitive decline. The researchers conclude, “Our findings suggest that clinical management of dyslipidemia with statins in ART-adherent HIV individuals may reduce the risk of midlife cognitive decline, and a window of opportunity likely occurs between ages of 50 and 65 years.”