Objective HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Design Retrospective analysis of tissue bank specimens and pre-mortem data. Methods 58 HIV+ adults underwent medical and neurocognitive evaluation within one year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the Epigenetic Clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. Results The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. Conclusions This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects.

Events leading to and propagating neurocognitive impairment (NCI) in HIV-1-infected (HIV+) persons are largely mediated by peripheral blood monocytes. We previously identified expression levels of individual genes and gene networks in peripheral blood monocytes that correlated with neurocognitive functioning in HIV+ adults. Here, we expand upon those findings by examining if gene expression data at baseline is predictive of change in neurocognitive functioning 2 years later. We also attempt to validate the original findings in a new sample of HIV+ patients and determine if the findings are HIV specific by including HIV-uninfected (HIV-) participants as a comparison group. At two time points, messenger RNA (mRNA) was isolated from the monocytes of 123 HIV+ and 60 HIV- adults enrolled in the Multicenter AIDS Cohort Study and analyzed with the Illumina HT-12 v4 Expression BeadChip. All participants received baseline and follow-up neurocognitive testing 2 years after mRNA analysis. Data were analyzed using standard gene expression analysis and weighted gene co-expression network analysis with correction for multiple testing. Gene sets were analyzed for GO term enrichment. Only weak reproducibility of associations of single genes with neurocognitive functioning was observed, indicating that such measures are unreliable as biomarkers for HIV-related NCI; however, gene networks were generally preserved between time points and largely reproducible, suggesting that these may be more reliable. Several gene networks associated with variables related to HIV infection were found (e.g., MHC I antigen processing, TNF signaling, interferon gamma signaling, and antiviral defense); however, no significant associations were found for neurocognitive function. Furthermore, neither individual gene probes nor gene networks predicted later neurocognitive change. This study did not validate our previous findings and does not support the use of monocyte gene expression profiles as a biomarker for current or future HIV-associated neurocognitive impairment.

No abstract

No abstract

Objective A previous meta-analysis assessing the impact of heart failure (HF) on cognition found the HF group performed more poorly than the healthy control (HC) on global cognition measures. The study observed a medium effect and moderate heterogeneity when using the Mini-Mental Status Examination (MMSE) to measure HF’s impact on global cognition. The current meta-regression explores whether the mean age of the HF group moderates performance on the MMSE when comparing HF patients to HC. Data Selection Two researchers independently searched eight databases, extracted data, and calculated effect sizes as part of a larger study. Inclusion criteria were: (a) adults with a diagnosis of HF, (b) comparison of HF patients to HC, and (c) adequate data to calculate effect sizes. Articles were excluded if patients had other types of organ failure, the article was not available in English, or there was a risk of sample overlap with another included study. Twelve articles (HF n = 1166 and HC n = 1948) were included. The unrestricted maximum likelihood computational model was used for the meta-regression. Data Synthesis Studies included in the meta-regression evidenced a statistically significant medium effect size estimate with moderate heterogeneity (k = 12, g = 0.671, p < 0.001, I2 = 80.91%). The meta-regression was statistically significant (slope = −0.023, p = 0.0022, Qmodel = 5.26, df = 1, p = 0.022). Conclusions Individuals with HF performed more poorly on the MMSE than HC. Larger effect sizes on the MMSE were observed in studies with participants who were younger compared to studies with participants who were older. Future research should continue to delineate the impact of age on global cognition in individuals with HF.