Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

Abstract

Objective To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. Design This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children ages 1–6 years participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Methods Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z-scores (WAZ), antiretroviral therapy (ART) status and immunological biomarkers. Results 111 children were included in the final analysis. Lower levels of CD4+ CD38+ T-cells (p=0.04) were associated to higher Immediate and Total Recall scores (p=0.04). Higher levels of CD8+ HLA-DR+ T-cells were associated with higher Total Recall score (p=0.04) of the COAT. Higher CD4+ CD38+ HLA-DR+ T-cells levels were associated with higher Gross Motor scores of the MSEL (p=0.02). WAZ was positively correlated to Visual Reception, Fine Motor, Expressive Language and composite score of the MSEL. Conclusions Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4+ CD38+ T-cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship.

Associations between immunological function and memory recall in healthy adults

“…For example, decreased brain-derived neurotrophic factor (BDNF) production has been found in the brains of the CD4-depleted mice (Wolf et al, 2009). However, the current results are in line with previous human studies, for example in children with HIV infection (Ruisenor-Escudero et al, 2016). Also, in a study in healthy aging, better performance in memory and executive function were found for those with lower bloodderived CD4 T-cell counts and higher B-cell counts (Serre-Miranda et al, 2015).…”

“…Three levels of memory recall were evaluated, including immediate, short-and long delay memory recall. In particular, given Given findings from Ruisenor-Escudero et al (2016) and Kusdra et al (2000) we expected an inverse associations between memory recall and both CD4 + and CD8+. Given those of Grassi-Oliveira et al (2011), we anticipated an inverse association between memory recall and IL-6.…”

“…However, levels of CD4 + cells have been inversely associated with memory recallimmediate and stored memory in children infected with HIV (Ruisenor-Escudero et al, 2016) and short-term verbal memory, verbal working memory in older adults (Serre-Miranda et al, 2015). Other cells were also inversely associated with stored memory, including CD38 + and CD8+ (Ruisenor-Escudero et al, 2016). CD69 is also implicated in memory and has been found on monocytes derived from patients with Alzheimer's disease (Kusdra, Rempel, Yaffe, & Pulliam, 2000).…”

Scaling up Pediatric HIV Testing by Incorporating Provider-Initiated HIV Testing Into all Child Health Services in Hurungwe District, Zimbabwe

“…Disability is also likely to be associated with HIV infection in children as it had statistically significant odds ratios in the univariate model and the multivariate model that excluded mother’s HIV status. Neurocognitive impairment, developmental delays, and motor abnormalities such as spasticity have been observed among pediatric HIV patients, and may account for the high HIV prevalence among children with disability and likely association between disability and HIV infection in our study [35, 36]. Being malnourished likely reflects severe HIV disease and has been associated with disease progression and mortality in children [37].…”

Quality of Caregiving is Positively Associated With Neurodevelopment During the First Year of Life Among HIV-Exposed Uninfected Children in Uganda

“…We found a positive association between child HAZ and all MSEL sub-scales, including the Mullen Composite score. Previous studies from Uganda [40] and Tanzania [41] have found that wasting and stunting were independently associated with poorer psychomotor and neurodevelopmental outcomes. Given Uganda’s high prevalence of child undernutrition (estimated at 35% among children younger than 5 years) [42] and the high vulnerability to poor neurodevelopmental outcomes of undernourished infants affected by HIV, wasting and stunting should be considered as markers of children who might benefit from early neurodevelopment interventions coupled with nutritional support.…”