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Use of Neuroimaging to Inform Optimal Neurocognitive Criteria for Detecting HIV-Associated Brain Abnormalities
- Laura M. Campbell, Christine Fennema-Notestine, Rowan Saloner, Mariam Hussain, Anna Chen, Donald Franklin, Jr., Anya Umlauf, Ronald J. Ellis, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin B. Gelman, Ned Sacktor, Susan Morgello, J. Allen McCutchan, Scott Letendre, Igor Grant, Robert K. Heaton, for the CHARTER Group
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- Journal:
- Journal of the International Neuropsychological Society / Volume 26 / Issue 2 / February 2020
- Published online by Cambridge University Press:
- 02 October 2019, pp. 147-162
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Objective:
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Method:Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
Results:When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
Conclusions:The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Neurocognitive SuperAging in Older Adults Living With HIV: Demographic, Neuromedical and Everyday Functioning Correlates
- Rowan Saloner, Laura M. Campbell, Vanessa Serrano, Jessica L. Montoya, Elizabeth Pasipanodya, Emily W. Paolillo, Donald Franklin, Ronald J. Ellis, Scott L. Letendre, Ann C. Collier, David B. Clifford, Benjamin B. Gelman, Christina M. Marra, J. Allen McCutchan, Susan Morgello, Ned Sacktor, Dilip V. Jeste, Igor Grant, Robert K. Heaton, David J. Moore, the CHARTER and HNRP Groups
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- Journal:
- Journal of the International Neuropsychological Society / Volume 25 / Issue 5 / May 2019
- Published online by Cambridge University Press:
- 20 March 2019, pp. 507-519
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Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, 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)
Differences in Neurocognitive Impairment Among HIV-Infected Latinos in the United States
- María J. Marquine, Anne Heaton, Neco Johnson, Monica Rivera-Mindt, Mariana Cherner, Cinnamon Bloss, Todd Hulgan, Anya Umlauf, David J. Moore, Pariya Fazeli, Susan Morgello, Donald Franklin, Jr., Scott Letendre, Ron Ellis, Ann C. Collier, Christina M. Marra, David. B. Clifford, Benjamin B. Gelman, Ned Sacktor, David Simpson, J. Allen McCutchan, Igor Grant, Robert K. Heaton
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 2 / February 2018
- Published online by Cambridge University Press:
- 06 September 2017, pp. 163-175
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Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13–2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11–5.29; p=.03). Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163–175)
18 - HIV infection
- from Part II - Neurological diseases
- Albert Hofman, Erasmus Universiteit Rotterdam, Richard Mayeux, Columbia University, New York
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- Book:
- Investigating Neurological Disease
- Published online:
- 29 September 2009
- Print publication:
- 30 August 2001, pp 246-258
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Summary
Human immunodeficiency virus (HIV) infection has expanded to become a global pandemic which threatens health in most areas of the world, and is now the leading cause of death among some segments of the population. Infection with HIV-1, a member of the lentivirus subfamily of retroviruses, produces a wide spectrum of clinical manifestations, ranging from asymptomatic infection to severe, life-threatening opportunistic infections. The prevalence of HIV dementia is only 0.4% during the asymptomatic phase of infection. In patients with AIDS, dementia develops in 15-20%. The diagnosis of HIV dementia is established by a history of a progressive cognitive or behavioral decline with apathy, memory loss, or slowed mental processing and by appropriate ancillary studies. HIV-1 associated vacuolar myelopathy (HIV myelopathy) is characterized by a vacuolar degeneration affecting predominantly the thoracic spinal cord. Patients may have multiple concurrent opportunistic processes, or opportunistic processes may coexist with HIV-related neurological disorders.