Updated research nosology for HIV-associated neurocognitive disorders

Antinori, Andrea; Arendt, Gabriele; Becker, James T.; Brew, Bruce J.; Byrd, Desiree; Cherner, Mariana; Clifford, David B.; Cinque, Paola; Epstein, Leon G.; Goodkin, Karl; Gisslén, Magnus; Grant, Igor; Heaton, Robert K.; Joseph, Jeymohan; Marder, Karen; Marra, Christina M.; McArthur, Justin C.; Nunn, Michael; Price, Richard W.; Pulliam, Lynn; Robertson, Kevin; Sacktor, Ned; Valcour, Victor; Wojna, Valerie

doi:10.1212/01.wnl.0000287431.88658.8b

Cited by 2,356 publications

(2,732 citation statements)

References 21 publications

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“…Cognitive impairments are a recognized complication observed in 35–70% of persons infected with human immunodeficiency virus type one (HIV-1), including those who are both treated and untreated [1]–[5]. While combination antiretroviral therapy (cART) has robustly decreased the prevalence of HIV-associated dementia (HAD), milder forms of HIV-associated neurocognitive disorders (HAND) remain prevalent [1]–[3], [5], [6].…”

Section: Introductionmentioning

confidence: 99%

“…While combination antiretroviral therapy (cART) has robustly decreased the prevalence of HIV-associated dementia (HAD), milder forms of HIV-associated neurocognitive disorders (HAND) remain prevalent [1]–[3], [5], [6]. Despite such high prevalence, a differential diagnosis can often be difficult, requiring neurocognitive testing and exclusion of opportunistic infections, psychiatric disorders, drug toxicities, brain tumors, and other factors to rule out other causes.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

et al. 2013

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ObjectiveShortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation.MethodsHigh-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming.ResultsUninfected controls had increased neuronal synchronization in the 6–12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions.ConclusionsMEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

et al. 2013

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“…Before the training, each participant was assessed for estimated verbal intelligence quotient (IQ), full‐scale IQ, and completed tests within the seven cognitive domains required to diagnose HAND33 (Table 2). At each visit, all participants were assessed with nontrained near‐transfer WM tests (Digit‐Span and Letter‐Number Sequencing from Wechsler Adult Intelligence Scale‐Fourth Edition, and Spatial‐Span from the Wechsler Memory Scale‐Third Edition) and for depressive symptoms (Centers for Epidemiologic Studies‐Depression Scale; CES‐D) and self‐reported executive function in everyday life (Behavior Rating Inventory of Executive Function‐Adult Version; BRIEF‐A).…”

Section: Methodsmentioning

confidence: 99%

Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

Chang

Løhaugen

Andres

et al. 2016

Annals of Neurology

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ObjectiveWe aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A‐rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls.MethodsA total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near‐transfer WM tests (Digit‐Span, Spatial‐Span), self‐reported executive functioning, and functional magnetic resonance images during 1‐back and 2‐back tasks were performed at baseline and each follow‐up visit, and LMX1A‐rs4657412 was genotyped in all participants.ResultsAlthough HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A‐G carriers) also had poorer self‐reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A‐AA carriers (LMX1A genotype by HIV status, cluster‐corrected‐p < 0.0001).InterpretationAdaptive WMT, but not nonadaptive WMT, improved WM performance in both SN and HIV participants, and the accompanied decreased or normalized brain activation suggest improved neural efficiency, especially in HIV‐LMX1A‐AA carriers who might have greater dopaminergic reserve. These findings suggest that adaptive WMT may be an effective adjunctive therapy for WM deficits in HIV participants. ANN NEUROL 2017;81:17–34

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“…Although combination antiretroviral therapy (ART) is associated with improvements in neurocognition among persons living with HIV, many suffer from a spectrum of neuropsychological (NP) impairments known collectively as HIV‐associated neurocognitive disorders (HAND) despite ART (Antinori et al., 2007; Heaton, Clifford, Franklin, Woods, & Ake, 2010; Heaton, Franklin, Ellis, McCutchan, & Lentendre, 2011). HAND can manifest as difficulty with executive functioning, information processing speed, motor deficits, and/or memory deficits (Smith et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

“…HAND can manifest as difficulty with executive functioning, information processing speed, motor deficits, and/or memory deficits (Smith et al., 2014). Accordingly, neuropsychological batteries used for HAND diagnosis must be comprehensive in order to adequately assess several neurocognitive domains (Antinori et al., 2007). …”

Section: Introductionmentioning

confidence: 99%

Similar changes in neuropsychological functioning in english and spanish speaking HIV patients

et al. 2018

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ObjectivePrimary language has been reported to influence the results of neuropsychological (NP) testing. We sought to determine whether being a primary Spanish versus English speaker affects changes in neuropsychological evaluations in persons living with HIV.MethodData from 209 (188 English speakers and 21 Spanish speakers) ART‐naïve HIV‐infected adults were extracted from ACTG A5303, a 48‐week randomized clinical trial of two HIV treatment regimens. Participants’ mean (standard deviation) age and years of education were 35.1 (10.7) and 14.3 (2.7) years respectively. Changes from baseline to week 48 of antiretroviral therapy (ART) in individual, total, and domain z‐scores for NP tests and Global Deficit Scores (GDS) were compared between the primary languages using linear regression models, adjusted for baseline scores and years of education.ResultsBaseline demographic characteristics were comparable except Spanish speakers had less years of education than the English speakers (p < 0.001). Although differences in some NP measures and domains were detected at baseline, the adjusted changes in individual, total and domain NP z‐scores from baseline to 48 weeks of ART were not significantly different between the two primary language groups. The 48‐week changes in GDS were also similar.ConclusionChanges in NP during ART were similar between English and Spanish speaking HIV‐infected individuals for all NP measures. This suggests that studies of longitudinal changes in NP can pool participants across these languages.

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Updated research nosology for HIV-associated neurocognitive disorders

Cited by 2,356 publications

References 21 publications

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

Similar changes in neuropsychological functioning in english and spanish speaking HIV patients

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