HIV-Associated Neurocognitive Disorder (HAND): Obstacles to Early Neuropsychological Diagnosis

Vastag, Zsolt; Fira-Mlădinescu, Ovidiu; Roşca, Elena Cecilia

doi:10.2147/ijgm.s295859

Cited by 14 publications

(18 citation statements)

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“…Despite recent advances in managing and treating infected individuals, HIV-associated neurocognitive disorders (HAND) were reported in between 30 and 60% of adults [ 2 , 3 , 4 , 5 , 6 , 7 ]. Epidemiological studies report that HIV-associated dementia (HAD) is rare nowadays (2–4%) [ 7 ], and most PLWH present mild forms of cognitive dysfunction, including asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) [ 4 , 8 , 9 ]. A systematic review of the literature reported a pooled prevalence rate for HAD, according to the Frascati criteria of 5% (95% CI 3.5–6.8) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…The introduction of cART in 1996 was a landmark in HIV history, as effective this antiretroviral treatment decreased the severity of neurological impairments. Although the frequency of HAND did not decrease, with an unchanged prevalence of cognitive impairment in PLWH with systemic viral suppression, dementia is rare, while the milder, non-demented forms of HAND account for most cases [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Assessment and Diagnosis of HIV-Associated Dementia

Cornea

Lata²,

Simu

et al. 2023

Viruses

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The modern combined antiretroviral treatment (cART) for human immunodeficiency virus (HIV) infection has substantially lowered the incidence of HIV-associated dementia (HAD). The dominant clinical features include deficits in cognitive processing speed, concentration, attention, and memory. As people living with HIV become older, with high rates of comorbidities and concomitant treatments, the prevalence and complexity of cognitive impairment are expected to increase. Currently, the management of HAD and milder forms of HAND is grounded on the best clinical practice, as there is no specific, evidence-based, proven intervention for managing cognitive impairment. The present article acknowledges the multifactorial nature of the cognitive impairments found in HIV patients, outlining the current concepts in the field of HAD. Major areas of interest include neuropsychological testing and neuroimaging to evaluate CNS status, focusing on greater reliability in the exclusion of associated diseases and allowing for earlier diagnosis. Additionally, we considered the evidence for neurological involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the impact of the coronavirus (COVID-19) pandemic, with wider consequences to population health than can be attributed to the virus itself. The indirect effects of COVID-19, including the increased adoption of telehealth, decreased access to community resources, and social isolation, represent a significant health burden, disproportionately affecting older adults with dementia who have limited social networks and increased functional dependence on the community and health system. This synopsis reviews these aspects in greater detail, identifying key gaps and opportunities for researchers and clinicians; we provide an overview of the current concepts in the field of HAD, with suggestions for diagnosing and managing this important neurological complication, which is intended to be applicable across diverse populations, in line with clinical observations, and closely representative of HIV brain pathology.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment and Diagnosis of HIV-Associated Dementia

Cornea

Lata²,

Simu

et al. 2023

Viruses

Self Cite

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“…The proportion of people suffering from HAND has remained unchanged before and after the ART era (~20–30%), but the severity of the neurocognitive impairments has diminished from HIV-associated encephalopathy (HIVE) or dementia (HAD) to the predominance of less severe asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) phenotypes [ 4 , 16 , 30 , 31 , 32 ]. The diagnosis of HAND relies on neuropsychological testing and functional status assessments [ 4 , 33 ] although the presence of comorbidities such as age-related cognitive decline and related systemic diseases as well as the improved recognition of pre-existing mental disorders make the diagnosis of MND and ANI increasingly challenging [ 34 , 35 ]. Moreover, the determinants or a reliable diagnostic biomarker for HAND and the mechanisms underpinning HIV persistence in the brain, together with the impact of this reservoir on the brain’s microenvironment, remain uncertain.…”

Section: Introductionmentioning

confidence: 99%

The HIV Restriction Factor Profile in the Brain Is Associated with the Clinical Status and Viral Quantities

Mohammadzadeh

Zhang

Branton

et al. 2023

Viruses

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HIV-encoded DNA, RNA and proteins persist in the brain despite effective antiretroviral therapy (ART), with undetectable plasma and cerebrospinal fluid viral RNA levels, often in association with neurocognitive impairments. Although the determinants of HIV persistence have garnered attention, the expression and regulation of antiretroviral host restriction factors (RFs) in the brain for HIV and SIV remain unknown. We investigated the transcriptomic profile of antiretroviral RF genes by RNA-sequencing with confirmation by qRT-PCR in the cerebral cortex of people who are uninfected (HIV[−]), those who are HIV-infected without pre-mortem brain disease (HIV[+]), those who are HIV-infected with neurocognitive disorders (HIV[+]/HAND) and those with neurocognitive disorders with encephalitis (HIV[+]/HIVE). We observed significant increases in RF expression in the brains of HIV[+]/HIVE in association with the brain viral load. Machine learning techniques identified MAN1B1 as a key gene that distinguished the HIV[+] group from the HIV[+] groups with HAND. Analyses of SIV-associated RFs in brains from SIV-infected Chinese rhesus macaques with different ART regimens revealed diminished RF expression among ART-exposed SIV-infected animals, although ART interruption resulted in an induced expression of several RF genes including OAS3, RNASEL, MX2 and MAN1B1. Thus, the brain displays a distinct expression profile of RFs that is associated with the neurological status as well as the brain viral burden. Moreover, ART interruption can influence the brain’s RF profile, which might contribute to disease outcomes.

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“…However, it is difficult to accurately diagnose ANI at present. Diagnosis requires a series of neurocognitive scale tests, which are time-consuming, and the results are easily affected by various factors, such as the patient's education level, environment, and examiner ( 9 , 10 ). In addition, these patients have no obvious clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment

Han

Aili

et al. 2022

Front. Neurol.

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ObjectiveAsymptomatic neurocognitive impairment (ANI) is a predominant form of cognitive impairment in young HIV-infected patients. However, the neurophysiological mechanisms underlying this disorder have not been clarified. We aimed to evaluate the altered patterns of functional brain activity in young HIV-infected patients with ANI by quantifying regional homogeneity (ReHo) and region of interest (ROI)-based functional connectivity (FC).MethodsThe experiment involved 44 young HIV-infected patients with ANI and 47 well-matched healthy controls (HCs) undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and neurocognitive tests. Reho alterations were first explored between the ANI group and HC groups. Subsequently, regions showing differences in ReHo were defined as ROIs for FC analysis. Finally, the correlation of ReHo and FC with cognitive function and clinical variables was assessed.ResultsCompared with HCs, ANI patients had a significant ReHo decrease in the right lingual gyrus (LING. R), right superior occipital gyrus (SOG. R), left superior occipital gyrus (SOG. L), left middle occipital gyrus (MOG. L), right middle frontal gyrus (MFG. R), cerebellar vermis, ReHo enhancement in the left middle frontal gyrus (MFG. L), and left insula (INS L). The ANI patients showed increased FC between the LING. R and MOG. L compared to HC. For ANI patients, verbal and language scores were negatively correlated with increased mean ReHo values in the MFG.L. Increased mean ReHo values in the INS. L was positively correlated with disease duration—the mean ReHo values in the LING. R was positively correlated with the abstraction and executive function scores. Increased FC between the LING. R and MOG. L was positively correlated with verbal and language performance.ConclusionThe results suggest that the visual network might be the most vulnerable area of brain function in young HIV-infected patients with ANI. The middle frontal gyrus, cerebellar vermis, and insula also play an important role in asymptomatic neurocognitive impairment. The regional homogeneity and functional connectivity of these regions have compound alterations, which may be related to the course of the disease and neurocognitive function. These neuroimaging findings will help us understand the characteristics of brain network modifications in young HIV-infected patients with ANI.

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HIV-Associated Neurocognitive Disorder (HAND): Obstacles to Early Neuropsychological Diagnosis

Cited by 14 publications

References 82 publications

Assessment and Diagnosis of HIV-Associated Dementia

Assessment and Diagnosis of HIV-Associated Dementia

The HIV Restriction Factor Profile in the Brain Is Associated with the Clinical Status and Viral Quantities

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment

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