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1. The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning

Author

Levine, AJ, Reynolds, S, Cox, C, Miller, EN, Sinsheimer, JS, Becker, JT, Martin, E, and Sacktor, N

Subjects
Clinical Sciences, Medical Microbiology, Neurosciences, Virology
Abstract

Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect one's risk for neurocognitive impairment. Literature on both HIV and stimulant use indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study, the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning were examined longitudinally over a 10-year period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-highly active antiretroviral therapy (HAART) data were examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No four-way interactions were found, indicating that HIVand stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple three-way interactions were found that involved genotype and HIV status. All immunologically related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only C-C chemokine ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologically related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however, their impact is minor. Being consistent with findings from another cohort, dopamine (DA)-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV+ individuals. © Journal of NeuroVirology, Inc. 2014.

Published
2014

2. Systolic Blood Pressure within an Intermediate Range May Reduce Memory Loss in an Elderly Hypertensive Cohort

Author

Sacktor, N, Gray, S, Kawas, C, Herbst, J, Costa, P, and Fleg, J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Hypertension, Cardiovascular, Clinical Research, Aging, Aged, Antihypertensive Agents, Blood Pressure, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Memory Disorders, Middle Aged, Neuropsychological Tests, Retrospective Studies, Severity of Illness Index, Neurosciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

The objective of this study was to determine if maintenance of systolic blood pressure (BP) within a high range or low range among treated hypertensive patients increases the risk of memory decline. Biennial neuropsychological evaluations were performed on 158 hypertensive subjects. Decline/year was measured on the Cued Selective Reminding test (total free recall and delayed recall) in three systolic BP groups (low-i.e., mean systolic BP during the follow-up period < 135 mm Hg; intermediate-i.e., 135 mm Hg < or = mean systolic BP < or = 150 mm Hg; high-i.e., mean systolic BP > 150 mm Hg). In total free recall, the three systolic BP groups had significantly different declines per year (P = .02), with patients in the high subgroup showing the greatest decline. In delayed recall, the three systolic BP groups also showed significantly different declines per year (P = .04), with patients in the low subgroup having the greatest decline. Chronically elevated systolic BP > 150 mm Hg is associated with accelerated memory decline compared to older treated hypertensive patients with systolic BP in an intermediate range. Chronically maintained systolic BP within a low normal range < 135 mm Hg in older treated hypertensive subjects may be associated with accelerated memory decline, specifically in a test of delayed memory recall, compared to patients with systolic BP in an intermediate range. Optimal regulation of systolic BP may be a potential modifiable risk factor to prevent or minimize memory loss in older hypertensive patients.

Published
1999

3. International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271

Author

Robertson, K., Jiang, H., Evans, S. R., Marra, C. M., Berzins, B., Hakim, J., Sacktor, N., Silva, M. Tulius, Campbell, T. B., Nair, A., Schouten, J., Kumwenda, J., Supparatpinyo, K., Tripathy, S., Kumarasamy, N., la Rosa, A., Montano, S., Mwafongo, A., Firnhaber, C., Sanne, I., Naini, L., Amod, F., Walawander, A., With the 5271 study team, and for the AIDS Clinical Trials Group

Published
2016
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5. Peripheral inflammation and depressed mood independently predict neurocognitive worsening over 12 years

Author

Tang, Bin, primary, Collier, A.C., additional, Morgello, S., additional, Cookson, D., additional, Sacktor, N., additional, Ellis, Ronald J., additional, Marra, Christina M., additional, Clifford, David B., additional, Gelman, Benjamin B., additional, Robinson-Papp, Jessica, additional, McCutchan, J. Allen, additional, Letendre, Scott, additional, Heaton, Robert K., additional, and Grant, Igor, additional

Published
2022
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10. White matter damage, neuroinflammation, and neuronal integrity in HAND

Author

Alakkas, A, Ellis, RJ, Watson, CW-M, Umlauf, A, Heaton, RK, Letendre, S, Collier, A, Marra, C, Clifford, DB, Gelman, B, Sacktor, N, Morgello, S, Simpson, D, McCutchan, JA, Kallianpur, A, Gianella, S, Marcotte, T, Grant, I, Fennema-Notestine, C, and CHARTER Group

Subjects
CD4-Positive T-Lymphocytes, Adult, Male, AIDS Dementia Complex, Anti-HIV Agents, Clinical Sciences, Antiretroviral Therapy, Neuroimaging, Neuropsychological Tests, HAND, Severity of Illness Index, Basal Ganglia, Choline, Memory, Clinical Research, Virology, Acquired Cognitive Impairment, Humans, 2.1 Biological and endogenous factors, Highly Active, Cognitive Dysfunction, Longitudinal Studies, Gray Matter, Aetiology, Aspartic Acid, Neurosciences, Organ Size, Middle Aged, Creatine, Magnetic Resonance Imaging, White Matter, CD4 Lymphocyte Count, Brain Disorders, Infectious Diseases, Mental Health, Short-Term, Hand Mri, Medical Microbiology, CHARTER Group, Neurological, Biomedical Imaging, HIV/AIDS, Female, MRI
Abstract

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N-acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.

Published
2019

17. HIV-Associated Cognitive Impairment before and after the Advent of Combination Therapy

Author

Sacktor, N., Mcdermott, M. P., Marder, K., Schifitto, G., Selnes, O. A., Mcarthur, J. C., Yaakov Stern, Albert, S., Palumbo, D., Kieburtz, K., Marcaida, J. A., Cohen, B., and Epstein, L.

Subjects
Cognition disorders, Highly active antiretroviral therapy, Neurology, Neuropsychology, virus diseases, Dementia, HIV-positive persons
Abstract

The objective of this study was to describe the occurrence of HIV dementia and neuropsychological testing abnormalities in a new cohort of HIV-seropositive individuals at high risk for HIV dementia and to compare these results to a cohort before the advent of highly active antiretroviral therapy (HAART). HAART has been associated with improvements in cognitive performance in some HIV-infected patients. However, it is uncertain whether HAART has changed the frequency of specific neurocognitive abnormalities. Baseline data from 272 HIV-seropositive subjects in the Dana cohort recruited from January, 1994, to December, 1995, and 251 HIV-seropositive subjects in the Northeastern AIDS Dementia Consortium (NEAD) cohort recruited from April, 1998, to August, 1999, were compared. Participants in both cohorts received nearly identical assessments. After adjusting for differences in age, education, gender, race, and CD4 count between the two cohorts, there were no differences in the occurrence of HIV dementia or abnormalities either 1 SD or 2 SDs below established norms for any of the neuropsychological tests. Even though HAART has reduced the incidence of HIV dementia, HIV-associated cognitive impairment continues to be a major clinical problem among individuals with advanced infection.

Published
2002
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29. Updated research nosology for HIV-associated neurocognitive disorders

Author

Antinori, A., primary, Arendt, G., additional, Becker, J. T., additional, Brew, B. J., additional, Byrd, D. A., additional, Cherner, M., additional, Clifford, D. B., additional, Cinque, P., additional, Epstein, L. G., additional, Goodkin, K., additional, Gisslen, M., additional, Grant, I., additional, Heaton, R. K., additional, Joseph, J., additional, Marder, K., additional, Marra, C. M., additional, McArthur, J. C., additional, Nunn, M., additional, Price, R. W., additional, Pulliam, L., additional, Robertson, K. R., additional, Sacktor, N., additional, Valcour, V., additional, and Wojna, V. E., additional

Published
2007
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34. Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia

Author

Sevigny, J. J., primary, Albert, S. M., additional, McDermott, M. P., additional, McArthur, J. C., additional, Sacktor, N., additional, Conant, K., additional, Schifitto, G., additional, Selnes, O. A., additional, Stern, Y., additional, McClernon, D. R., additional, Palumbo, D., additional, Kieburtz, K., additional, Riggs, G., additional, Cohen, B., additional, Epstein, L. G., additional, and Marder, K., additional

Published
2004
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