Neuropsychological Function and Cerebral Metabolites in HIV-infected Youth

Abstract

The effects of HIV on brain metabolites and cognitive function are not well understood. Sixteen HIV+youths (15 vertical, 1 transfusion transmissions) receiving combination antiretroviral therapy and 14 age-matched HIV-youths (13–25 years of age) were evaluated with brain two-dimensional (2D) magnetic resonance spectroscopy (MRS) at 3 Tesla (T) and a neuropsychological battery that assessed three cognitive domains (attention/processing speed, psychomotor ability, and executive function). The relationship between brain metabolite ratios and cognitive performance was explored. Compared to HIV− controls, HIV+subjects had higher sycllo-inositol (Scy)/total creatine (tCr) (+32%, p=0.016) and higher Scy/total choline (tCho) (+31%, p=0.018) on 2D-MRS in the right frontal lobe. HIV+ subjects also had higher glutamate (Glu)/tCr (+13%, p=0.022) and higher Glu/tCho (+15%, p=0.048) than controls. HIV+subjects demonstrated poorer attention/processing speed (p=0.011, d=1.03) but similar psychomotor and executive function compared to HIV− controls. The attention/processing score also correlated negatively with the ratio of N-acetylaspartate (NAA) to tCr on 2D-MRS (r=−0.75, p=0.0019) in the HIV− controls, but not in the HIV+ subjects (Fisher’s r-z transformation, p<0.05). Our results suggest that attention/processing speed is impacted by early HIV infection and is associated with right hemisphere NAA/tCr. Scy and Glu ratios are also potential markers of brain health in chronic, lifelong HIV infection in perinatally infected youths receiving antiretroviral therapy.

Executive Functioning in Children and Adolescents With Perinatal HIV Infection and Perinatal HIV Exposure

“…It is also consistent with a larger literature that shows that processing speed is a cognitive domain at particular risk for those with HIV infection [6,13,[32][33][34][35]. Processing speed has demonstrated associations with markers of both past [29] and ongoing disease processes, such as functional connectivity using functional magnetic resonance imaging [36], brain metabolites [14], and biomarkers of vascular functioning [37], in youth with PHIV. Longitudinal studies regarding cognitive functions such as processing speed or academic skills such as reading that might underlie EF problems in this population might identify targets for prevention and intervention and early indicators of a need for EF intervention.…”

“…However, this cohort was relatively young, which leaves open the possibility that differences might emerge in adolescence or young adulthood as EF skills continue to develop. Similarly, in a study of 554 youth aged 7 to 16 years [14], EF differences between youth with PHIV and PHEU youth were attributed to risk factors other than HIV for the majority of the sample; however, a subgroup with PHIV and previous encephalopathy had significantly slower performance and more self-reported problems in metacognition even after adjustment for demographic factors. In addition, EF measures differed from age-referenced norms for the PHIV and PHEU groups, which suggests a risk for EF dysfunction in both populations.…”

“…The results of earlier studies of relatively small groups of children with PHIV have varied regarding the existence of EF deficits [13][14][15] and their relationship to other cognitive processes such as attention, which are also required for performance of higher-level goal-directed behaviors. In a study of 161 children aged 8 to 12 years [16], EF differences were observed between those with PHIV and those who were perinatally HIV exposed but uninfected (PHEU); however, the differences were not significant after adjustment for psychosocial risk factors such as parental education, which suggests that the observed EF differences were not wholly attributable to HIV infection.…”

Impact of human immunodeficiency virus on neurocognition and risky behaviors in young adults

“…Results of a previous study revealed that perinatally infected HIV+ individuals between ages 13 and 25 performed significantly more poorly on tests of attention and processing speed than age matched HIV- controls (Nagarajan et al 2012). More recently, Nichols and colleagues demonstrated a high prevalence of HAND within a relatively large sample of horizontally infected HIV+ young adults between the ages of 18 and 24 naïve to treatment.…”

Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

“…One study used a neuropsychological battery to assess the cognitive domains of attention/ processing speed, psychomotor ability, and problemsolving skills in 16 PHIV adolescents. The results showed that the performance of the PHIV youths was poorer compared to the control group, which consisted of agematched HIV-uninfected volunteers [44] . In regard to mental health, the incidence of psychiatric disorders is higher among PHIV adolescents and uninfected youths belonging to HIV-infected families compared to the general population [45][46][47] .…”