Researchers Report New Insights Into HIV-Related Neurocognitive Disorders

The use of antiretroviral therapy (ART) has allowed patients with HIV to have a life expectancy that approaches the lifespan of those without HIV. Despite this progress, however, HIV-associated neurocognitive disorders remain prevalent, and range from mild problems with memory, language, and reasoning to more severe HIV-associated dementia.

Frailty has also emerged as an age-related comorbidity in patients with HIV, and at the recent American Neurological Association 2019 meeting, held in St. Louis, Missouri, researchers reported on efforts to use deep learning algorithms of cerebral blood flow to classify both cognitive impairment and frailty in patients living with HIV, and said that they were able to predict brain regions for each domain, and to identify brain regions that overlap between cognitive impairment and frailty.¹

In the study, 125 patients with HIV who were virologically suppressed using combination ART were enrolled. The mean age was 51.4 (standard deviation, 11.4 years). All of the participants were given a neuropsychological battery, were assessed for frailty, and had structural neuroimaging performed.

Deep neural network models were trained to classify participants as unimpaired or impaired, and as frail, prefrail, or nonfrail using Fried phenotype criteria, which rely on weight loss, exhaustion, low physical activity, slowness, and weakness.

The strongest cerebral blood flow predictors of frailty were in the subcortical regions: the amygdala, caudate, hippocampus, thalamus, pallidum, and cerebellum.

Meanwhile, the strongest predictors of cognitive impairment were both cortical (parietal, occipital, and temporal) and subcortical (amygdala, caudate, and hippocampus). For both cognitive impairment and frailty, the amygdala, caudate and hippocampus were strong predictors.

“Our results suggest frailty in HIV is primarily a subcortical disease while cognitive impairment in HIV involves subcortical and cortical brain regions with regards to [cerebral blood flow],” write the authors.

Another research team also shared findings on HIV-associated neurocognitive impairment, and said that heme oxygenase-1 (HO-1), a cytoprotective enzyme that limits oxidative stress, inflammation, and cellular injury within the central nervous system, can predict risk for impairment in African American patients with HIV.²

In HO-1 expression, modulated through a promoter repeat polymorphism, shorter alleles with fewer repeats are linked with higher HO-1 transcription and are linked with better outcomes in a number of diseases, say the authors. In a cohort of 606 individuals with HIV, say the authors, there was a reduced risk of functional neurocognitive impairment among those with short repeats. Compared with Caucasian patients, African American patients had higher-risk genotypes with longer alleles, so the presence of a short HO-1 allele had a greater protective effect against neurocognitive impairment in these patients.

Therapeutic strategies that include HO-1 expression should be investigated, say the researchers, because they could reduce the risk for development and progression of HIV-associated neurocognitive impairment.

References

1. Luckett PH, Paul RH, Navid J, et al. Deep learning analysis of cerebral blood flow to identify cognitive impairment ad frailty in persons living with HIV. Presented at: the American Neurological Association’s 2019 Annual Meeting; October 13-15, 2019; St. Louis, Missouri. Abstract M116.

2. Gill A, Garza R, Garcia-Mesa Y, et al. Heme oxygenase-1 promoter (GT)n polymorphism predicts risk for neurocognitive impairment in HIV-infected individuals with higher-risk genotypes in African-Americans. Presented at: the American Neurological Association’s 2019 Annual Meeting; October 13-15, 2019; St. Louis, Missouri. Abstract S248.