Disrupted brain networks in the aging HIV+ population

Abstract

Antiretroviral therapies have become widely available, and as a result, individuals infected with the human immunodeficiency virus (HIV) are living longer, and becoming integrated into the geriatric population. Around half of the HIV + population shows some degree of cognitive impairment, but it is unknown how their neural networks and brain connectivity compare to those of noninfected people. Here we combined magnetic resonance imaging-based cortical parcellations with high angular resolution diffusion tensor imaging tractography in 55 HIV-seropositive patients and 30 age-matched controls, to map white matter connections between cortical regions. We set out to determine selective virus-associated disruptions in the brain's structural network. All individuals in this study were aged 60-80, with full access to antiretroviral therapy. Frontal and motor connections were compromised in HIV + individuals. HIV + people who carried the apolipoprotein E4 allele (ApoE4) genotype-which puts them at even greater risk for neurodegeneration-showed additional network structure deficits in temporal and parietal connections. The ApoE4 genotype interacted with duration of illness. Carriers showed greater brain network inefficiencies the longer they were infected. Neural network deficiencies in HIV + populations exceed those typical of normal aging, and are worse in those genetically predisposed to brain degeneration. This work isolates neuropathological alterations in HIV + elders, even when treated with antiretroviral therapy. Network impairments may contribute to the neuropsychological abnormalities in elderly HIV patients, who will soon account for around half of all HIV + adults.

Breakdown of Brain Connectivity Between Normal Aging and Alzheimer's Disease: A Structuralk-Core Network Analysis

“…Diffusion imaging may be used in conjunction with an automatically labeled set of regions from anatomical MRI to perform connectivity mapping and network analysis of the brain's fiber connections. Many analyses of brain connectivity have been conducted in this way (Dennis et al, 2012a, b;Dennis and Thompson, 2012;Jahanshad et al, 2011Jahanshad et al, , 2012Zalesky, 2009;Zhan et al, 2012). Connectivity matrices were compiled using a processing pipeline described previously (Braskie et al, 2012a, b;Dennis et al, 2012b;Jahanshad et al, 2011Jahanshad et al, , 2012Nir et al, 2012a, b).…”

Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits

“…22 This finding is also consistent with the more widespread deficits in brain structural connectivity (on diffusion tensor imaging scans) in HIV1 APOE e4 subjects. 31 These discrepancies in the effects of APOE e4 on HAND may also be partly attributable to racial differences among cohorts. A large longitudinal study found that only white but not black individuals with APOE e41 showed faster decline in semantic and working memory.…”

Common genetic variants and gene expression associated with white matter microstructure in the human brain

“…Fractional anisotropy (FA) is an index of the extent to which this motion is directionally constrained and, as validated in animal (Li et al, 2011) and post-mortem research (Schmierer et al, 2007), it reflects a combination of myelin thickness, fiber coherence and axon integrity. Studies using a priori selected candidate genes and SNPs have associated FA with genetic variation in NRG1 (McIntosh et al, 2008; Sprooten et al, 2009; Winterer et al, 2008), ErbB4 (Konrad et al, 2009; Zuliani et al, 2011), DISC1 (Sprooten et al, 2011b), NTRK1 (Braskie et al, 2012), BDNF (Chiang et al, 2011a) and APOE (Jahanshad et al, 2012), amongst others. However, FA is a complex, polygenic phenotype and for most complex phenotypes data-driven GWA have not implicated a priori candidate variants in their top results (Flint and Munafo, 2013; Stein et al, 2012), hence many more novel SNP-associations contributing to variation in FA could be discovered using GWA.…”