Mapping the brain in younger and older asymptomatic HIV-1 men: Frontal volume changes in the absence of other cortical or diffusion tensor abnormalities

Towgood, Karren; Pitkänen, Mikko R. A.; Kulasegaram, Ranjababu; Fradera, Alex; Kumar, Atul; Soni, Suneetha; Sibtain, Naomi; Reed, Laurence; Bradbeer, Caroline; Barker, Gareth J.; Kopelman, Michael

doi:10.1016/j.cortex.2011.03.006

Cited by 96 publications

(108 citation statements)

References 82 publications

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“…Older individuals displayed a loss of periventricular, frontal, and temporal WM. These results were partly replicated in a work of Towgood et al, 31 who also noted volume reduction in the medial and superior frontal regions related to HIV infection. In the same vein, Ances et al 32 reported a significant volume reduction in several subcortical areas (amygdala, caudate, and corpus callosum) related to HIV, as well as a decrease in caudate volume related to aging.…”

Section: Neuroimagingsupporting

confidence: 61%

“…However, it was significant only for the controls. By contrast, Towgood et al 31 failed to obtain a significant serostatus effect on several measures of diffusivity in a cross-sectional study, although a significant aging effect was observed in several brain regions including frontotemporal WM. The lack of significance of serostatus was explained as related to the early and asymptomatic stage at which HIV+ individuals were evaluated and the difficulty of detecting subtle white matter alterations.…”

Section: Neuroimagingmentioning

confidence: 76%

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HIV and Aging: Effects on the Central Nervous System

2014

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With the introduction of combination antiretroviral therapy, many human immunodeficiency virus-positive (HIV+) individuals are reaching advanced age. The proportion of people living with HIV older than 50 years already exceeds 50% in many communities, and is expected to reach this level nationally by 2015. HIV and aging are independently associated with neuropathological changes, but their concurrence may have a more deleterious effect on the central nervous system (CNS). Published data about neurocognitive and neuroimaging markers of HIV and aging are reviewed. Putative factors contributing to neurocognitive impairment and neuroimaging changes in the aging HIV+ brain, such as metabolic disturbances, cardiovascular risk factors, immune senescence, and neuroinflammation, are described. The possible relationship between HIV and some markers of Alzheimer’s disease is presented. Current research findings emphasize multiple mechanisms related to HIV and combination antiretroviral therapy that compromise CNS structure and function with advancing age.

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Section: Neuroimagingsupporting

confidence: 61%

Section: Neuroimagingmentioning

confidence: 76%

HIV and Aging: Effects on the Central Nervous System

2014

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“…We note that relative lack of differences between the HIV− and HIV+ samples is unlikely to be explained by an abnormal amount of WM damage in the HIV− sample as those were screened for any history of neurological, psychiatric, alcohol, and substance misuse as well as acute cardio-vascular diseases (Cysique et al 2013), while their neurocognitive functions are within the expected normal range ). Moreover, another study also detected no differences in MD and FA between their HIV− and HIV+ sample (Towgood et al 2012). Because their main study aim was to assess the effects of HIV and aging on brain functions, they did not explore further reasons for this lack of difference.…”

Section: Discussionmentioning

confidence: 99%

“…resulted in inconsistent results. Moreover, variations in the studied HIV+ participants in relation to their combination antiretroviral (cART) status, level of viral suppression, the nature of HIV disease , and their demographics (mainly age) (Towgood et al 2012;Chang et al 2008;Gongvatana et al 2011;Seider et al 2015) have probably contributed to a lack of consistency. Altogether, while DTI may be useful at characterizing the extent of WM injury in cases with moderate to severe HIV-associated neurocognitive disorder (HAND) (Chang et al 2008;Chen et al 2009;Gongvatana et al 2011) or advanced untreated HIV infection (Hoare et al 2011;Leite et al 2013;Pfefferbaum et al 2009) (when HIV replication is the cause of the WM damage), its use at elucidating what may be the HIV-related neuropathology substrate in virally suppressed HIV infection is less clear.…”

Section: Introductionmentioning

confidence: 99%

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

et al. 2017

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The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV− and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm 2 ; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p < 0.05-0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD (p < 0.01-0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD (p = 0.04-p < 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration.

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“…[3][4][5][6][7] Recent neuroimaging studies have used advanced magnetic resonance imaging (MRI) techniques such as diffusionweighted (DWI) and diffusion tensor imaging (DTI), [8][9][10] volumetric analysis 11,12 and arterial spin labeling 13 to explore biomarkers of HIV infection and of NCI in HIV + patients. In particular, research using diffusion-based techniques suggests that HIV infection and HIV-associated NCI are associated with increased diffusivity and reduced anisotropy in cerebral white matter (WM).…”

Section: Introductionmentioning

confidence: 99%

Cross-Sectional Study of Unexplained White Matter Lesions in HIV Positive Individuals Undergoing Brain Magnetic Resonance Imaging

Haddow

Dudau

Chandrashekar

et al. 2014

AIDS Patient Care and STDs

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White matter (WM) abnormalities are frequently seen on brain MRI of HIV positive (HIV + ) patients. We aimed to determine the prevalence of unexplained WM abnormalities and their associations with HIV disease and cardiovascular risk factors. We conducted a retrospective, cross-sectional study of brain MRI of HIV + patients conducted between 2004 and 2009 at our center. Clinical and laboratory data were compiled, and images were independently reviewed for WM lesions. Images were obtained from 254 patients: 70% male, 53% white, 40% black, mean age 42 years, median current CD4 count 240 cells/mm 3 , and 41% not taking antiretroviral therapy (ART). Hyperintense WM lesions were present in 161 patients (63.4%): 89 scans (35.0%) showed diffuse WM signal abnormality (DWMSA), 61 (24.0%) were consistent with small vessel disease (SVD, graded by Fazekas' scale), and 37 (14.6%) showed large asymmetrical focal WM lesions. SVD changes were associated with age and cardiovascular risk factors, and while cerebral SVD may be related to HIV infection, the MRI findings were not associated with HIV-related factors. The only risk factor for DWMSA was black race, and no correlation with cardiovascular risk factors, CD4 count, or clinical presentation was identified. DWMSA are therefore of uncertain neurological significance in HIV + patients and could represent more than one clinicopathological entity.

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Mapping the brain in younger and older asymptomatic HIV-1 men: Frontal volume changes in the absence of other cortical or diffusion tensor abnormalities

Cited by 96 publications

References 82 publications

HIV and Aging: Effects on the Central Nervous System

HIV and Aging: Effects on the Central Nervous System

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

Cross-Sectional Study of Unexplained White Matter Lesions in HIV Positive Individuals Undergoing Brain Magnetic Resonance Imaging

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