HIV-Associated Neurocognitive Disorders

2019 ◽  
pp. 27-60
Author(s):  
Jennifer E.  Iudicello ◽  
Erin E. Morgan ◽  
Mariam A. Hussain ◽  
Caitlin Wei-Ming Watson ◽  
Robert K. Heaton
Keyword(s):  
Differential Diagnosis ◽  
Neurocognitive Impairment ◽  
Hiv Treatment ◽  
People Living With Hiv ◽  
Neurocognitive Disorder ◽  
Diagnostic Systems ◽  
Neurocognitive Performance ◽  
Everyday Functioning ◽  
Asymptomatic Neurocognitive Impairment ◽  
Age Related

Human immunodeficiency virus enters the central nervous system (CNS) early after systemic infection, and may cause neural injury and associated neurocognitive impairment through multiple direct and indirect mechanisms. An international conference of multidisciplinary neuroAIDS experts convened in 2005 to propose operationalized research criteria for HIV-related cognitive and everyday functioning impairments. The resulting classification system, known as the Frascati criteria, defined three types of HIV-associated neurocognitive disorder (HAND): asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia (HAD). Consideration of comorbid conditions that can influence neurocognitive performance, such as developmental disabilities, non-HIV forms of CNS compromise (neurological and systemic), severe psychiatric conditions, and substance use disorders, is essential to differential diagnosis. Since the introduction of combination antiretroviral therapy (ART), rates of severe HAND (i.e., HAD) have greatly declined, although the milder forms of HAND remain quite prevalent, even in virally suppressed people living with HIV (PLWH). Beyond ART, clinical management of HAND includes behavioral interventions focused on neurocognitive and functional improvements. This chapter covers a range of HAND-related topics, such as the neuropathological mechanisms of HIV-related CNS injury, assessment and diagnostic systems for neurocognitive and everyday functioning impairment in HIV, treatment and protective factors, aging with HIV, HAND in international settings, and ongoing challenges and controversies in the field. Future needs for progress with HAND include advances in early detection of mild cognitive deficits and associated functional impairment in PLWH; biomarkers that may be sensitive to its underlying pathogenesis; and differential diagnosis of HAND versus age-related, non-HIV-associated disorders.

scholarly journals Psycho-behavioral factors associated with neurocognitive performance among people living with HIV on antiretroviral therapy in Accra, Ghana

2020 ◽  
Vol 20 (2) ◽  
pp. 587-596
Author(s):  
Nana Asiedu ◽  
Irene Kretchy ◽  
Emmanuel Asampong
Keyword(s):  
Operating Characteristic ◽  
Neurocognitive Impairment ◽  
People Living With Hiv ◽  
Neurocognitive Performance ◽  
Factors Associated ◽  
Non Invasive ◽  
Hiv Management ◽  
Behavioural Factors ◽  
Living With Hiv ◽  
Selection Of

Background: It is estimated that almost half of all people living with HIV have some form of neurocognitive impairment, but few studies have looked at the risk of neurocognitive impairment and its associated factors in Ghana, due in part to limited resources for such testing. Objective: To examine neurocognitive performance in a group of Ghanaians living with HIV and possible factors that contribute to their performance. Methods: One hundred and four patients were assessed using a selection of brief non-invasive neuropsychological assess- ments as well as the International HIV Dementia Scale. Psycho-behavioural factors (alcohol use, depression, and medication adherence) as well as demographic characteristics and functional daily activities were assessed to determine their association with neurocognitive performance, using linear regression and receiver operating characteristic analyses. Results: About 48% of the participants met the criteria for risk of neurocognitive impairment. Age, education, and symp- toms of depression were found to be significantly associated with the risk of impairment. Conclusion: Some people living with HIV showed risk of neurocognitive impairment, which was significantly associated with education, age and depressive symptoms. It is therefore important to consider routine neurocognitive screening in HIV management to recognize any risks for early interventions. Keywords: ART adherence; depression; neurologic disease.

Global prevalence and burden of HIV-associated neurocognitive disorder

Neurology ◽  
2020 ◽  
Vol 95 (19) ◽  
pp. e2610-e2621 ◽  
Author(s):  
Yunhe Wang ◽  
Moxuan Liu ◽  
Qingdong Lu ◽  
Michael Farrell ◽  
Julia M. Lappin ◽  
...  
Keyword(s):  
Data Extraction ◽  
Sub Saharan Africa ◽  
People Living With Hiv ◽  
Neurocognitive Disorder ◽  
Cross Sectional ◽  
Asymptomatic Neurocognitive Impairment ◽  
Cd4 Cell Count ◽  
Hiv Associated Neurocognitive Disorder ◽  
Sub Saharan ◽  
High Level

ObjectiveTo characterize the prevalence and burden of HIV-associated neurocognitive disorder (HAND) and assess associated factors in the global population with HIV.MethodsWe searched PubMed and Embase for cross-sectional or cohort studies reporting the prevalence of HAND or its subtypes in HIV-infected adult populations from January 1, 1996, to May 15, 2020, without language restrictions. Two reviewers independently undertook the study selection, data extraction, and quality assessment. We estimated pooled prevalence of HAND by a random effects model and evaluated its overall burden worldwide.ResultsOf 5,588 records identified, we included 123 studies involving 35,513 participants from 32 countries. The overall prevalence of HAND was 42.6% (95% confidence interval [CI] 39.7–45.5) and did not differ with respect to diagnostic criteria used. The prevalence of asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia were 23.5% (20.3–26.8), 13.3% (10.6–16.3), and 5.0% (3.5–6.8) according to the Frascati criteria, respectively. The prevalence of HAND was significantly associated with the level of CD4 nadir, with a prevalence of HAND higher in low CD4 nadir groups (mean/median CD4 nadir <200 45.2% [40.5–49.9]) vs the high CD4 nadir group (mean/median CD4 nadir ≥200 37.1% [32.7–41.7]). Worldwide, we estimated that there were roughly 16,145,400 (95% CI 15,046,300–17,244,500) cases of HAND in HIV-infected adults, with 72% in sub-Saharan Africa (11,571,200 cases, 95% CI 9,600,000–13,568,000).ConclusionsOur findings suggest that people living with HIV have a high burden of HAND in the antiretroviral therapy (ART) era, especially in sub-Saharan Africa and Latin America. Earlier initiation of ART and sustained adherence to maintain a high-level CD4 cell count and prevent severe immunosuppression is likely to reduce the prevalence and severity of HAND.

scholarly journals Association between HIV infection and neurocognitive disorders: a review

2021 ◽  
Author(s):  
Rafael Felipe Silva Rodrigues ◽  
Ana Luiza Soares Henriques de Almeida ◽  
Amanda Mansur Rosa ◽  
Suelen Darlane Vieira ◽  
Luciana Maria Campos e Silva ◽  
...  
Keyword(s):  
Viral Load ◽  
Life Expectancy ◽  
Highly Active Antiretroviral Therapy ◽  
Brain Aging ◽  
Neurocognitive Disorders ◽  
Brain Inflammation ◽  
People Living With Hiv ◽  
Neurocognitive Disorder ◽  
Asymptomatic Neurocognitive Impairment ◽  
The Impact

Background: HIV-associated neurocognitive disorders (HAND) are characterized by impairment in at least two cognitive domains with a prevalence of up to 50% in people living with HIV (PLHIV). HAND is subdivided into asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD). Objectives: Demonstrate the impact of HAND and possible pathogenic mechanisms by relating them to the prevalence of subtypes Design and Setting: Review of the literature. Methods: Review made from PubMed with the descriptors “neurocognitive disorder”, “HIV”, “review”. Twelve articles were selected, among systematic reviews and meta-analysis published since 2017. Results: Before Highly Active Antiretroviral Therapy (HAART) HAD cases had a higher prevalence, probably due to the high viral load causing intense brain inflammation. Today the percentage of HAD has decreased, but the cases of ANI and MND continue to increase. HAART increases life expectancy and reduces viral load, but it may be related to the increase in ANI / MND associated with early brain aging and mild inflammatory processes resulting from primary infection. Conclusions: HAND is a concern for its impact on the quality of life and life expectancy of PLHIV. Therefore, neuropsychological assessment is an important tool for early diagnosis and disease management. The change in prevalence of different HAND subtypes raises doubts about the pathogenesis of these conditions and further studies are needed to elucidate this issue and develop therapeutic solutions.

scholarly journals Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics

2018 ◽  
Vol 19 (11) ◽  
pp. 3594 ◽  
Author(s):  
Ian Olivier ◽  
Ramón Cacabelos ◽  
Vinogran Naidoo
Keyword(s):  
Risk Factors ◽  
Immune Response ◽  
Human Genetics ◽  
Hiv Treatment ◽  
Specific Gene ◽  
People Living With Hiv ◽  
Neurocognitive Disorder ◽  
Host Genetics ◽  
Hiv Associated Neurocognitive Disorder

Neurocognitive impairments associated with human immunodeficiency virus (HIV) infection remain a considerable health issue for almost half the people living with HIV, despite progress in HIV treatment through combination antiretroviral therapy (cART). The pathogenesis and risk factors of HIV-associated neurocognitive disorder (HAND) are still incompletely understood. This is partly due to the complexity of HAND diagnostics, as phenotypes present with high variability and change over time. Our current understanding is that HIV enters the central nervous system (CNS) during infection, persisting and replicating in resident immune and supporting cells, with the subsequent host immune response and inflammation likely adding to the development of HAND. Differences in host (human) genetics determine, in part, the effectiveness of the immune response and other factors that increase the vulnerability to HAND. This review describes findings from studies investigating the role of human host genetics in the pathogenesis of HAND, including potential risk factors for developing HAND. The similarities and differences between HAND and Alzheimer’s disease are also discussed. While some specific variations in host genes regulating immune responses and neurotransmission have been associated with protection or risk of HAND development, the effects are generally small and findings poorly replicated. Nevertheless, a few specific gene variants appear to affect the risk for developing HAND and aid our understanding of HAND pathogenesis.

scholarly journals Prevalence and Correlates of Neurocognitive Disorders among HIV Patients on Antiretroviral Therapy at a Kenyan Hospital

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
A. G. Mugendi ◽  
M. N. Kubo ◽  
D. G. Nyamu ◽  
L. M. Mwaniki ◽  
S. K. Wahome ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Clinical Care ◽  
Neurocognitive Impairment ◽  
Neurocognitive Disorders ◽  
Cd4 Count ◽  
People Living With Hiv ◽  
Hiv Diagnosis ◽  
Cross Sectional ◽  
Asymptomatic Neurocognitive Impairment ◽  
Living With Hiv

Background. HIV-associated neurocognitive disorders (HAND) represent a spectrum of cognitive abnormalities affecting attention, concentration, learning, memory, executive function, psychomotor speed, and/or dexterity. Our objectives in this analysis are to determine the prevalence of HAND and the covariates in a Kenyan population. Methods. We conducted a cross-sectional study in a convenient sample of people living with HIV on antiretroviral therapy (ART) attending routine care visits at the Kenyatta National Hospital HIV clinic between July and August 2015. Baseline demographics were obtained using interviewer-administered questionnaires; clinical data were abstracted from patient records. Trained research clinicians determined the neurocognitive status by administration of the International HIV Dementia Scale (IHDS), the Montreal Cognitive Assessment (MOCA) scale, and the Lawton Instrumental Activities of Daily Living (IADL) scale. Cognitive impairment was defined as a score of ≤26 on the MOCA and ≤10 on the IHDS. Descriptive analysis and logistic regression to determine predictors of screening positive for HAND were done with the significance value set at <0.05. Results. We enrolled 345 participants (202 men; 143 women). The mean age of the study population was 42 years (±standard deviation (SD) 9.5). Mean duration since HIV diagnosis and mean duration on ART were 6.3 (±SD 3.7) and 5.6 years (±SD 3.4), respectively. Median CD4 count at interview was 446 cells/mm3 (interquartile range (IQR) 278–596). Eighty-eight percent of participants screened positive for HAND, of whom 87% had asymptomatic neurocognitive impairment (ANI) and minor neurocognitive disorders (MND) grouped together while 1% had HIV-associated dementia (HAD). Patients on AZT/3TC/EFV were 3.7 times more likely to have HAND (OR = 3.7, p=0.03) compared to other HAART regimens. In the adjusted analysis, women were more likely to suffer any form of HAND than men (aOR = 2.17, 95% CI: 1.02, 4.71; p=0.045), whereas more years in school and a higher CD4 count (aOR = 0.58, 95% CI: 0.38, 0.88; p=0.012), (aOR = 0.998, 95% CI 0.997, 0.999; p=0.013) conferred a lowered risk. Conclusion. Asymptomatic and mild neurocognitive impairment is prevalent among people living with HIV on treatment. Clinical care for HIV-positive patients should involve regular screening for neurocognitive disorders while prioritizing women and those with low education and/or low CD4 counts.

scholarly journals Exploring Substance Use and HIV Treatment Factors Associated with Neurocognitive Impairment among People Living with HIV/AIDS

2014 ◽  
Vol 2 ◽  
Author(s):  
Jennifer M. Attonito ◽  
Jessy G. Dévieux ◽  
Brenda D. G. Lerner ◽  
Michelle M. Hospital ◽  
Rhonda Rosenberg
Keyword(s):  
Substance Use ◽  
Neurocognitive Impairment ◽  
Hiv Treatment ◽  
People Living With Hiv ◽  
Factors Associated ◽  
Living With Hiv ◽  
Hiv Aids

scholarly journals Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania

2021 ◽  
pp. 1-12
Author(s):  
Aidan Flatt ◽  
Tom Gentry ◽  
Johanna Kellett-Wright ◽  
Patrick Eaton ◽  
Marcella Joseph ◽  
...  
Keyword(s):  
Clinical Care ◽  
Self Report ◽  
Sub Saharan Africa ◽  
Hiv Care ◽  
People Living With Hiv ◽  
Neurocognitive Disorder ◽  
Low Literacy ◽  
Asymptomatic Neurocognitive Impairment ◽  
Incidence Studies ◽  
Clinical Records

Abstract Objectives: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. Design: Longitudinal study Participants: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017. Measurements: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. Results: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed. Conclusions: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Depressive symptoms and level of physical activity mediate the associations between HIV sero-status and neurocognitive functions among individuals aged at least 50 years in China (Preprint)

2021 ◽  
Author(s):  
Pei Qin ◽  
Jianmei He ◽  
Xue Yang ◽  
Siyu Chen ◽  
Xi Chen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Depressive Symptoms ◽  
Older People ◽  
Processing Speed ◽  
Neurocognitive Impairment ◽  
People Living With Hiv ◽  
Neurocognitive Performance ◽  
Living With Hiv ◽  
Negative Controls ◽  
Hiv Negative

BACKGROUND Neurocognitive impairment are prevalent among older people. It is more problematic among older people living with HIV (PLWH). This study was to explore whether the association between HIV sero-status and neurocognitive performance was mediated by depressive symptoms and/or level of physical activity. OBJECTIVE Neurocognitive impairment are prevalent among older people in China. It is more problematic among older people living with HIV (PLWH). This study was to compare neurocognitive performance between older PLWH and HIV-negative controls, and to explore whether the association between HIV sero-status and neurocognitive performance was mediated by depressive symptoms and/or level of physical activity. METHODS A cross-sectional study was conducted in Yongzhou, China. All PLWH aged ≥50 years listed in the registry were invited. Frequency matching was used to sample HIV-negative controls according to the distribution of age, sex, and years of formal education of older PLWH. A total of 315 older PLWH and 350 HIV-negative controls completed the face-to-face interview and comprehensive neuropsychological assessment of seven domains (learning, memory, working memory, verbal fluency, processing speed, executive function and motor skills). RESULTS As compared to HIV-negative controls, older PLWH performed worse in global score and all seven domains (P<.05). Positive HIV sero-status was associated with higher depressive symptoms (P<.001) and lower level of physical activity (P<.001). Depressive symptoms and physical activity were negatively correlated (P<.001). Depressive symptoms and/or level of physical activity mediated the association between HIV sero-status and global score and four domain-specific neurocognitive performance (learning, memory, verbal fluency, and processing speed). CONCLUSIONS Change in mental health and physical activity after HIV infection may partially explain why older PLWH are more susceptible to neurocognitive impairment. Promoting mental health and physical activity are potential entry points to slow down the progress of neurocognitive impairment among older PLWH.

scholarly journals The University of California San Diego performance-based skills assessment: a useful tool to detect mild everyday functioning difficulties in HIV-infected patients with very good immunological condition

2020 ◽  
Vol 26 (6) ◽  
pp. 899-907
Author(s):  
Valentina Delle Donne ◽  
Nicoletta Ciccarelli ◽  
Valentina Massaroni ◽  
Alberto Borghetti ◽  
Alex Dusina ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
San Diego ◽  
University Of California ◽  
Cognitive Domain ◽  
Skills Assessment ◽  
People Living With Hiv ◽  
Neurocognitive Performance ◽  
Everyday Functioning ◽  
The University ◽  
Immunological Condition

AbstractEveryday functioning (EF) impairment is frequent in people living with HIV (PLWH). Our aim was to better explore EF and its association with PLWH cognition, by administering both the IADL scale, the most common functional scale, and a new and ecologic multi-domain (communication and financial skills) tool to measure EF as the University of California San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B). Eighty-five PLWH on cART with very good immunological condition and 23 age- and education-matched healthy controls (HC) were enrolled. PLWH underwent a standardized neuropsychological battery plus IADL, and cognitive impairment was defined according to Frascati criteria. Both groups underwent the UPSA-B. Only 6 subjects (7%) were affected by cognitive impairment (asymptomatic profile). While IADL score was at ceiling for all patients, the UPSA-B total score was significantly worse in PLWH when compared with HC [mean 82.1 (SD 9.3) vs 89.2 (SD 6.2); p < 0.001]. At communication subtest, PLWH group and HC were significantly different (p = 0.002), while no difference emerged at financial skills (p = 0.096). Higher score at UPSA-B was independently associated with better global cognitive performance (composite Z-score) (β 7.79; p < 0.001). Also considering each single cognitive domain, UPSA-B performance (both total and at subtests) confirmed the association with neurocognitive performance. In conclusion, UPSA-B seems to better discriminate EF impairment than IADL in PLWH, and it was associated with cognitive functions, also in the absence of symptomatic cognitive impairment. Thus, it appears a promising tool in the context of HIV infection to avoid misdiagnosis and to better detect also mild EF.

scholarly journals Neurocognitive SuperAging in Older Adults Living With HIV: Demographic, Neuromedical and Everyday Functioning Correlates

2019 ◽  
Vol 25 (05) ◽  
pp. 507-519 ◽  
Author(s):  
Rowan Saloner ◽  
Laura M. Campbell ◽  
Vanessa Serrano ◽  
Jessica L. Montoya ◽  
Elizabeth Pasipanodya ◽  
...  
Keyword(s):  
Older Adults ◽  
Multinomial Logistic Regression ◽  
Future Research ◽  
Hiv Disease ◽  
Neurocognitive Performance ◽  
Everyday Functioning ◽  
Disease Characteristics ◽  
Age Related ◽  
Persons Living With Hiv ◽  
Living With Hiv

Objectives:Studies of neurocognitively elite older adults, termedSuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA.Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status.Results:Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA.Conclusions:Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019,25, 507–519)

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