Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease

Milanini, Benedetta; Samboju, Vishal; Cobigo, Yann; Paul, Robert; Javandel, Shireen; Hellmuth, Joanna; Allen, Isabel Elaine; Miller, Bruce L.; Valcour, Victor

doi:10.1016/j.neurobiolaging.2019.07.006

Cited by 19 publications

(21 citation statements)

References 54 publications

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“…Although the severity of HAND is lowered by cART, people living with HIV (PLWH), continue to display high rates of cognitive impairment and often develop Alzheimer’s disease (AD) earlier in life compared to the general population ( Calcagno et al, 2021 ; Sharma, 2021 ). As high intracellular iron worsens HIV-1 prognosis and iron proteins are upregulated in HAND, ferroptosis-induced neurodegeneration (FIN) may contribute to this disorder ( Patton et al, 2017 ; Milanini et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

et al. 2022

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Graphical AbstractBoth HIV-1 and cART alter the lysosomes, increasing intracellular iron and the risk of ferroptosis. Dysfunctional lysosomes release the ferroptosis drivers iron, Ca2+ and cathepsin B (catB), promoting neuronal and oligodendrocyte loss, reflected in the white and gray matter pathology. The host responds to lysosomal damage by activating an epigenetic axis comprised of bromodomain 4 (BRD4) and microRNA-29 family (miR-29) that promptly suppresses lysosomal function, lowering ferritinophagy. As there is an inverse relationship between miR-29 and BRD4, HIV-1 inhibition of miR-29, upregulates BRD4, blocking ferritinophagy. The BRD4/miR-29 system also inhibits iron regulatory protein-2 (IRP-2) and augments cystine/glutamate antiporter xCT (SLC7A11), lowering the odds of ferroptosis.

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Section: Introductionmentioning

confidence: 99%

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

et al. 2022

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“…An animal study of Chinese rhesus macaques showed that the basal ganglia had the highest detection rate of SIV [ 26 ]. The volume of the putamen is susceptible in the early stages of HIV infection, and shrinks further as the infection progresses [ 27 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

Early prediction of putamen imaging features in HIV-associated neurocognitive impairment syndrome

Wang

et al. 2021

BMC Neurol

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Background To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain cognitive impairment through radiomics. Method Retrospective selection of 90 patients with HIV infection, including 36 asymptomatic neurocognitive impairment (ANI) patients and 54 pre-clinical ANI patients in Beijing YouAn Hospital. All patients received comprehensive neuropsychological assessment and MRI scanning. 3D Slicer software was used to acquire volume of interest (VOI) and radiomics features. Clinical variables and volume of putamen were compared between patients with ANI and pre-clinical ANI. The Kruskal Wallis test was used to analysis multiple comparisons between groups. The relationship between cognitive scores and VOI was compared using linear regression. For radiomics, principal component analysis (PCA) was used to reduce model overfitting and calculations and then a support vector machine (SVM) was used to build a binary classification model. For model performance evaluation, we used an accuracy, sensitivity, specificity and receiver operating characteristic curve (ROC). Result There were no significant differences in clinical variables between ANI group and pre-clinical-ANI group (P>0.05). The volume of bilateral putamen was significantly different between AHI group and pre-clinical group (P<0.05), but there was only a trend in the left putamen between ANI-treatment group and pre-clinical treatment group(P = 0.063). Reduced cognitive scores in Verbal Fluency, Attention/Working Memory, Executive Functioning, memory and Speed of Information Processing were negatively correlated with the increased VOI (P<0.05), but the correlation was relatively low. In diagnosing the ANI from pre-clinical ANI, the mean area under the ROC curves (AUC) were 0.85 ± 0.22, the mean sensitivity and specificity were 63.12 ± 5.51 and 94.25% ± 3.08%. Conclusion The volumes of putamen in patients with ANI may be larger than patients with pre-clinical ANI, the change of the volume of the putamen may have a certain process; there is a relationship between putamen and cognitive impairment, but the exact mechanism is unclear. Radiomics may be a useful tool for predicting early stage HAND in patients with HIV.

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“…Concentration of the virus is higher in selective brain regions including basal ganglia structures (Kumar, Ownby, Waldrop‐Valverde, Fernandez, & Kumar, 2011; Schier et al ., 2017), an integral part of the frontostriatal system, which is associated with executive functions, motor processes, and information processing speed (Ances, Ortega, Vaida, Heaps, & Paul, 2012; Hakkers et al ., 2017). Even after the introduction of HAART and in individuals whose viral level is well controlled, mild‐to‐moderate cognitive and motor deficits subserved by frontostriatal systems persist (Ipser et al ., 2015) with a threefold risk of HIV‐associated neurocognitive disorder (HAND) in older people with HIV infection (Milanini et al ., 2019; Valcour et al ., 2004).…”

Section: Introductionmentioning

confidence: 99%

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson’s disease

Müller‐Oehring

Fama

Levine

et al. 2020

Journal of Neuropsychology

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Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson's disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45-79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4 + T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.

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Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease

Cited by 19 publications

References 54 publications

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

Early prediction of putamen imaging features in HIV-associated neurocognitive impairment syndrome

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson’s disease

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