Publications by authors named "Leah H Rubin"

153 Publications

Body mass index and leptin are related to cognitive performance over 10 years in women with and without HIV infection.

J Clin Endocrinol Metab 2021 Oct 22. Epub 2021 Oct 22.

Department of Neurology, State University of New York Health Sciences University, Brooklyn, NY.

Objective: To determine whether body mass index (BMI) and leptin were longitudinally associated over 10 years with neuropsychological performance (NP) among middle-aged women with HIV (WWH) versus without HIV.

Methods: Women's Interagency HIV Study (WIHS) participants (301 WWH, 113 women without HIV from Brooklyn, New York City and Chicago had baseline and 10-year BMI (kg/m2) and fasting plasma leptin levels using commercial ELISA (ng/mL); and demographically-adjusted NP T-scores (attention/working memory, executive function (EF), processing speed, memory, learning, verbal fluency, motor function, global) at 10-year follow-up. Multivariable linear regression analyses, stratified by HIV-serostatus, examined associations between BMI, leptin, and NP.

Results: Over 10 years, women (baseline age 39.8+/-9.2 years, 73% Black, 73% WWH) transitioned from average overweight (29.1+/-7.9 kg/m 2) to obese (30.5+/-7.9 kg/m 2) BMI. Leptin increased 11.4+/-26.4 ng/mL (p<0.0001). Higher baseline BMI and leptin predicted poorer 10-year EF among all women (BMI B=-6.97, 95%CI(-11.5, -2.45) p=0.003; leptin B=-1.90, 95%CI(-3.03, -0.76), p=0.001); higher baseline BMI predicted better memory performance (B=6.35, 95%CI(1.96, 10.7), p=0.005). Greater 10-year leptin increase predicted poorer EF (p=0.004), speed (p=0.029), verbal (p=0.021) and global (p=0.005) performance among all women, and WWH. Greater 10-year BMI increase predicted slower processing speed (p=0.043) among all women; and among WWH, poorer EF (p=0.012) and global (p=0.035) performance.

Conclusions: In middle-aged WIHS participants, 10-year increases in BMI and leptin were associated with poorer performance across multiple NP domains among all and WWH. Trajectories of adiposity measures over time may provide insight into the role of adipose tissue in brain health with aging.
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http://dx.doi.org/10.1210/clinem/dgab759DOI Listing
October 2021

Sex-specific effects of low-dose hydrocortisone on threat detection in HIV.

J Neurovirol 2021 Sep 24. Epub 2021 Sep 24.

Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 6-113a, Baltimore, MD, 21287, USA.

One sex differences in the perception of emotion is that females, particularly those with high anxiety, often show heightened identification of fearful faces. To better understand the causal role of glucocorticoids in this sex difference, we examine these associations in people with HIV(PWH) where emotion perception is impaired and mental health disorders are frequent. In a double-blind, placebo-controlled, cross-over study, we used a single low-dose of hydrocortisone (10 mg; LDH) as a mechanistic probe of the effects of elevated glucocorticoids on negative emotion perception in 65 PWH (31 women). The primary outcome was accuracy in identifying emotional expressions on the Facial Emotion Perception Test (FEPT). Salivary cortisol, self-reported stress/anxiety, and childhood trauma were also assessed. LDH increased salivary cortisol levels versus placebo. The effect of LDH versus placebo on FEPT accuracy depended on the combined influence of facial expression and sex (P = 0.03). LDH influenced accuracy only for women (P = 0.03), specifically for fearful faces (Cohen's d = 0.44, P = 0.04). Women's enhanced threat detection varied with psychological burden (mood, anxiety, and post-traumatic stress symptoms), more pronounced among those with lower burden and trauma (P < 0.05). This result suggests a role of the HPA axis in sex differences for perception of fearful faces in women with HIV, potentially due to changes in glucocorticoid receptor availability/activity, or improved integration of signals from facial recognition and emotion processing regions. The blunting of this effect in men and in individuals with more severe trauma suggests that the mechanisms underlying threat detection differ by sex and trauma history and warrant further investigation.
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http://dx.doi.org/10.1007/s13365-021-01007-6DOI Listing
September 2021

Legacy effect on neuropsychological function in HIV-infected men on combination antiretroviral therapy.

AIDS 2021 Sep 13. Epub 2021 Sep 13.

Departments of Statistics, University of Pittsburgh Departments of Psychiatry, University of Pittsburgh Departments of Biostatistics, University of Pittsburgh Departments of Epidemiology, Graduate School of Public Health, University of Pittsburgh Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh Department of Neurology, David Geffen School of Medicine, UCLA Department of Psychiatry, Rush University School of Medicine Departments of Psychiatry, The Johns Hopkins University School of Medicine Department of Radiology, Northwestern University Neurology, The Johns Hopkins University School of Medicine Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University Departments of Neurology, University of Pittsburgh Departments of Psychology, University of Pittsburgh.

Objective: To determine whether cART initiation alters the trajectory of cognitive performance in HIV+ men, and whether cognition prior to cART predicts post-cART function.

Design: Longitudinal cohort study. Multicenter AIDS Cohort Study.

Methods: From an initial set of 3701 men with complete neuropsychological data, men with HIV infection were initially matched with men without infection on cognitive status, race, age, and timeline (T0 defined as cART initiation). Propensity score matching was then used to match pairs on depressive symptoms at T0, education, T0 cognitive scores, and recruitment cohort. There were 506 matched pairs of infected and uninfected men in the final analysis. Mixed effect models were constructed to analyze the trajectories of cognitive functions and to test the effect of cART and HIV on cognitive functions over time.

Results: Performance in each cognitive domain did not change following the initiation of cART among HIV-infected men with prior impairment and was comparable to the performance of their matched uninfected men. However, among the infected men who were unimpaired prior to cART, motor function declined significantly faster than it did for uninfected controls.

Conclusions: Cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself. Furthermore, motor skills may be uniquely vulnerable to the virus, cART, or age-related co-morbidities.
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http://dx.doi.org/10.1097/QAD.0000000000003071DOI Listing
September 2021

Tablet-Based Cognitive Impairment Screening for Adults With HIV Seeking Clinical Care: Observational Study.

JMIR Ment Health 2021 Sep 9;8(9):e25660. Epub 2021 Sep 9.

Johns Hopkins University, Baltimore, MD, United States.

Background: Neurological complications including cognitive impairment persist among people with HIV on antiretrovirals; however, cognitive screening is not routinely conducted in HIV clinics.

Objective: Our objective for this study was 3-fold: (1) to determine the feasibility of implementing an iPad-based cognitive impairment screener among adults seeking HIV care, (2) to examine the psychometric properties of the tool, and (3) to examine predictors of cognitive impairment using the tool.

Methods: A convenience sample of participants completed Brain Baseline Assessment of Cognition and Everyday Functioning (BRACE), which included (1) Trail Making Test Part A, measuring psychomotor speed; (2) Trail Making Test Part B, measuring set-shifting; (3) Stroop Color, measuring processing speed; and (4) the Visual-Spatial Learning Test. Global neuropsychological function was estimated as mean T score performance on the 4 outcomes. Impairment on each test or for the global mean was defined as a T score ≤40. Subgroups of participants repeated the tests 4 weeks or >6 months after completing the first test to evaluate intraperson test-retest reliability and practice effects (improvements in performance due to repeated test exposure). An additional subgroup completed a lengthier cognitive battery concurrently to assess validity. Relevant factors were abstracted from electronic medical records to examine predictors of global neuropsychological function.

Results: The study population consisted of 404 people with HIV (age: mean 53.6 years; race: 332/404, 82% Black; 34/404, 8% White, 10/404, 2% American Indian/Alaskan Native; 28/404, 7% other and 230/404, 58% male; 174/404, 42% female) of whom 99% (402/404) were on antiretroviral therapy. Participants completed BRACE in a mean of 12 minutes (SD 3.2), and impairment was demonstrated by 34% (136/404) on Trail Making Test A, 44% (177/404) on Trail Making Test B, 40% (161/404) on Stroop Color, and 17% (67/404) on Visual-Spatial Learning Test. Global impairment was demonstrated by 103 out of 404 (25%). Test-retest reliability for the subset of participants (n=26) repeating the measure at 4 weeks was 0.81 and for the subset of participants (n=67) repeating the measure almost 1 year later (days: median 294, IQR 50) was 0.63. There were no significant practice effects at either time point (P=.20 and P=.68, respectively). With respect for validity, the correlation between global impairment on the lengthier cognitive battery and BRACE was 0.63 (n=61; P<.001), with 84% sensitivity and 94% specificity to impairment on the lengthier cognitive battery.

Conclusions: We were able to successfully implement BRACE and estimate cognitive impairment burden in the context of routine clinic care. BRACE was also shown to have good psychometric properties. This easy-to-use tool in clinical settings may facilitate the care needs of people with HIV as cognitive impairment continues to remain a concern in people with HIV.
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http://dx.doi.org/10.2196/25660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461534PMC
September 2021

Working HAND in HAND: Central nervous system complications in people with HIV.

Clin Infect Dis 2021 Aug 20. Epub 2021 Aug 20.

Departments of Neurology and Radiology, Washington University in Saint Louis, Saint Louis, MO, United States.

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http://dx.doi.org/10.1093/cid/ciab723DOI Listing
August 2021

Improvement in depressive symptoms after antiretroviral therapy initiation in people with HIV in Rakai, Uganda.

J Neurovirol 2021 Aug 31;27(4):519-530. Epub 2021 Jul 31.

Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Meyer 6-113, Baltimore, MD, USA.

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aβ-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences.
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http://dx.doi.org/10.1007/s13365-020-00920-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524346PMC
August 2021

A Bayesian nonparametric approach for inferring drug combination effects on mental health in people with HIV.

Biometrics 2021 Jun 18. Epub 2021 Jun 18.

Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland, USA.

Although combination antiretroviral therapy (ART) with three or more drugs is highly effective in suppressing viral load for people with HIV (human immunodeficiency virus), many ART agents may exacerbate mental health-related adverse effects including depression. Therefore, understanding the effects of combination ART on mental health can help clinicians personalize medicine with less adverse effects to avoid undesirable health outcomes. The emergence of electronic health records offers researchers' unprecedented access to HIV data including individuals' mental health records, drug prescriptions, and clinical information over time. However, modeling such data is challenging due to high dimensionality of the drug combination space, the individual heterogeneity, and sparseness of the observed drug combinations. To address these challenges, we develop a Bayesian nonparametric approach to learn drug combination effect on mental health in people with HIV adjusting for sociodemographic, behavioral, and clinical factors. The proposed method is built upon the subset-tree kernel that represents drug combinations in a way that synthesizes known regimen structure into a single mathematical representation. It also utilizes a distance-dependent Chinese restaurant process to cluster heterogeneous populations while considering individuals' treatment histories. We evaluate the proposed approach through simulation studies, and apply the method to a dataset from the Women's Interagency HIV Study, showing the clinical utility of our model in guiding clinicians to prescribe informed and effective personalized treatment based on individuals' treatment histories and clinical characteristics.
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http://dx.doi.org/10.1111/biom.13508DOI Listing
June 2021

Genome-wide association study accounting for anticholinergic burden to examine cognitive dysfunction in psychotic disorders.

Neuropsychopharmacology 2021 09 18;46(10):1802-1810. Epub 2021 Jun 18.

Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.

Identifying genetic contributors to cognitive impairments in psychosis-spectrum disorders can advance understanding of disease pathophysiology. Although CNS medications are known to affect cognitive performance, they are often not accounted for in genetic association studies. In this study, we performed a genome-wide association study (GWAS) of global cognitive performance, measured as composite z-scores from the Brief Assessment of Cognition in Schizophrenia (BACS), in persons with psychotic disorders and controls (N = 817; 682 cases and 135 controls) from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Analyses accounting for anticholinergic exposures from both psychiatric and non-psychiatric medications revealed five significantly associated variants located at the chromosome 3p21.1 locus, with the top SNP rs1076425 in the inter-alpha-trypsin inhibitor heavy chain 1 (ITIH1) gene (P = 3.25×E-9). The inclusion of anticholinergic burden improved association models (P < 0.001) and the number of significant SNPs identified. The effect sizes and direction of effect of the top variants remained consistent when investigating findings within individuals receiving specific antipsychotic drugs and after accounting for antipsychotic dose. These associations were replicated in a separate study sample of untreated first-episode psychosis. The chromosome 3p21.1 locus was previously reported to have association with the risk for psychotic disorders and cognitive performance in healthy individuals. Our findings suggest that this region may be a psychosis risk locus that is associated with cognitive mechanisms. Our data highlight the general point that the inclusion of medication exposure information may improve the detection of gene-cognition associations in psychiatric genetic research.
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http://dx.doi.org/10.1038/s41386-021-01057-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358015PMC
September 2021

Plasma microRNAs are associated with domain-specific cognitive function in people with HIV.

AIDS 2021 09;35(11):1795-1804

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.

Objective: Cognitive impairment remains common in people with HIV (PWH) on antiretroviral therapy (ART). The clinical presentation and severity are highly variable in PWH suggesting that the pathophysiological mechanisms of cognitive complications are likely complex and multifactorial. MicroRNA (miRNA) expression changes may be linked to cognition as they are gene regulators involved in immune and stress responses as well as the development, plasticity, and differentiation of neurons. We examined plasma miRNA expression changes in relation to domain-specific and global cognitive function in PWH.

Design: Cross-sectional observational study.

Methods: Thirty-three PWH receiving care at the Southern Alberta Clinic, Canada completed neuropsychological (NP) testing and blood draw. Plasma miRNA extraction was followed by array hybridization. Random forest analysis was used to identify the top 10 miRNAs upregulated and downregulated in relation to cognition.

Results: Few miRNAs were identified across cognitive domains; however, when evident a miRNA was only associated with two or three domains. Notably, miR-127-3p was related to learning/memory and miR-485-5p to motor function, miRNAs previously identified in CSF or plasma in Alzheimer's and Parkinson's, respectively. Using miRNET 2.0, a software-platform for understanding the biological relevance of the miRNA-targets (genes) relating to cognition through a network-based approach, we identified genes involved in signaling, cell cycle, and transcription relating to executive function, learning/memory, and language.

Conclusion: Findings support the idea that evaluating miRNA expression (or any molecular measure) in the context of global NP function might exclude miRNAs that could be important contributors to the domain-specific mechanisms leading to the variable neuropsychiatric outcomes seen in PWH.
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http://dx.doi.org/10.1097/QAD.0000000000002966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524348PMC
September 2021

Construct and Criterion-Related Validity of the Clinical Frailty Scale in Persons With HIV.

J Acquir Immune Defic Syndr 2021 Sep;88(1):110-116

Departments of Neurology and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD; and.

Background: The co-occurrence of frailty and cognitive impairment in older (50+ years) persons with HIV (PWH) is common and increases the risk of poor outcomes. In HIV clinics, the most commonly used frailty measures are the frailty phenotype (FP), which requires measuring grip strength and gait speed to implement, and the frailty index (FI) based on comprehensive health data collected on patients. We examined construct and criterion-related validity (as it predicts cognition) of the Clinical Frailty Scale (CFS), a less resource-intensive approach for assessing frailty, in relation to these more commonly used frailty assessments (FP and FI).

Setting/methods: A total of 143 older (age 50+) PWH (mean age 57 years; 88% male) seen at the Southern Alberta Clinic underwent both frailty screening with the FP, CFS, and FI and neuropsychological testing. Mixed-effects regressions examined the associations between frailty status and cognition.

Results: Concordance with the FP was slightly superior for the CFS than the FI. The FP and CFS had similar associations with domain-specific cognitive performance with frail PWH performing worse than nonfrail individuals on tests requiring manual dexterity (Trail Making Part A and B; Symbol Digit; and Grooved Pegboard; P values <0.05). Neither were associated with executive function, learning, or memory performance. The FI was associated with worse fluency, fine motor skills (Grooved Pegboard), and Trail Making Part A.

Conclusion: The CFS is a simple screening tool with good construct and criterion-related validity. It was associated with a similar pattern of cognitive deficits as the FP. If confirmed and the associations are extended to other clinically significant characteristics and outcomes, the CFS can be considered as an alternative to the FP and FI in assessing frailty in older PWH.
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http://dx.doi.org/10.1097/QAI.0000000000002736DOI Listing
September 2021

Psychosocial Stress Alters the Immune Response and Results in Higher Viral Load During Acute SIV Infection in a Pigtailed Macaque Model of HIV.

J Infect Dis 2021 May 10. Epub 2021 May 10.

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: While social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general (1) and in the context of infectious disease, such as HIV (2,3). A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection.

Methods: To determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n=35) and socially (n=41) housed SIV-infected pigtailed macaques (Macaca nemestrina).

Results: Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T cell declines and more CD4 and CD8 T cell activation compared to socially housed macaques throughout acute SIV infection.

Conclusions: These data demonstrate that psychosocial stress directly impacts the pathogenesis of acute SIV infection and imply that it may act as an integral variable in the progression of HIV infection and potentially of other viral infections.
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http://dx.doi.org/10.1093/infdis/jiab252DOI Listing
May 2021

Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy.

Neurology 2021 07 4;97(2):e156-e165. Epub 2021 May 4.

From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA.

Objective: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures.

Methods: In this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures.

Results: Sixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32-65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm (SD 97 cells/mm, range 1-416 cells/mm) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147-657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) ( = -0.344, = 0.04) and sural nerve amplitude ( = -0.359, = 0.004).

Conclusions: Both IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy.
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http://dx.doi.org/10.1212/WNL.0000000000012142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279564PMC
July 2021

Higher circulating intermediate monocytes are associated with cognitive function in women with HIV.

JCI Insight 2021 Jun 8;6(11). Epub 2021 Jun 8.

Department of Psychiatry and Behavioral Sciences, and.

BACKGROUNDIdentifying a quantitative biomarker of neuropsychiatric dysfunction in people with HIV (PWH) remains a significant challenge in the neuroHIV field. The strongest evidence to date implicates the role of monocytes in central nervous system (CNS) dysfunction in HIV, yet no study has examined monocyte subsets in blood as a correlate and/or predictor of neuropsychiatric function in virally suppressed PWH.METHODSIn 2 independent cohorts of virologically suppressed women with HIV (vsWWH; n = 25 and n = 18), whole blood samples were obtained either in conjunction with neuropsychiatric assessments (neuropsychological [NP] test battery, self-report depression and stress-related symptom questionnaires) or 1 year prior to assessments. Immune cell subsets were assessed by flow cytometry.RESULTSA higher proportion of intermediate monocytes (CD14+CD16+) was associated with lower global NP function when assessing monocytes concurrently and approximately 1 year before (predictive) NP testing. The same pattern was seen for executive function (mental flexibility) and processing speed. Conversely, there were no associations with monocyte subsets and depression or stress-related symptoms. Additionally, we found that a higher proportion of classical monocytes was associated with better cognition.CONCLUSIONAlthough it is widely accepted that lentiviral infection of the CNS targets cells of monocyte-macrophage-microglial lineage and is associated with an increase in intermediate monocytes in the blood and monocyte migration into the brain, the percentage of intermediate monocytes in blood of vsWWH has not been associated with neuropsychiatric outcomes. Our findings provide evidence for a new, easily measured, blood-based cognitive biomarker in vsWWH.FUNDINGR01-MH113512, R01-MH113512-S, P30-AI094189, R01-MH112391, R01-AI127142, R00-DA044838, U01-AI35004, and P30-MH075673.
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http://dx.doi.org/10.1172/jci.insight.146215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262276PMC
June 2021

Dietary intake is associated with neuropsychological impairment in women with HIV.

Am J Clin Nutr 2021 07;114(1):378-389

Department of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco, San Francisco, CA, USA.

Background: Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives: We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods: An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = 50; SD = 10) ≤40 at ≥1 visit after completing the dietary screener. Multivariable logistic regression, stratified by HIV serostatus, examined associations between intake frequency tertile (referent = lowest intake) and NP performance.

Results: Dietary intake frequencies of individual food line items were similar between WWH and HIV-seronegative women, except for sweet beverages, for which HIV-seronegative women reported higher intake frequencies than WWH (P values < 0.05). In WWH, multivariable-adjusted models indicated higher odds of NP impairment with higher intake frequencies of processed meat [P = 0.006; ORupper tertile = 1.91 (95% CI: 1.23-2.95; P = 0.003); ORmiddle tertile = 1.66 (95% CI: 1.14-2.42; P = 0.01)], sweet beverages [P = 0.02; ORupper tertile = 1.75 (95% CI: 1.17-2.64; P = 0.007)], fish [P = 0.01; ORupper tertile = 1.70 (95% CI: 1.10-2.64; P = 0.02)], and whole milk [P = 0.029; ORupper tertile = 1.66 (95% CI: 1.14-2.42; P = 0.008)]. Lower odds of NP impairment [P = 0.005; ORupper tertile = 0.65 (95% CI: 0.45-0.95; P = 0.02); ORmiddle tertile = 0.42 (95% CI: 0.24-0.73; P = 0.002)] were associated with higher vegetable intakes. In HIV-seronegative women, multivariable-adjusted models did not show associations between food line items/diet quality score and NP outcomes.

Conclusions: Intakes of processed meat, sweet beverages, whole milk, fish, and vegetables may be associated with NP functions among WWH. Associations among WWH are not directly comparable to those among HIV-seronegative women, because models were conducted on each group separately given controls for HIV-specific covariates in WWH. Further studies are needed using more rigorous dietary assessment methods and lengthier longitudinal follow-ups.
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http://dx.doi.org/10.1093/ajcn/nqab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246600PMC
July 2021

Assessment, prevalence, and correlates of frailty among middle-aged adults with HIV in rural Uganda.

J Neurovirol 2021 Jun 31;27(3):487-492. Epub 2021 Mar 31.

Johns Hopkins University School of Medicine, Baltimore, USA.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.
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http://dx.doi.org/10.1007/s13365-021-00969-xDOI Listing
June 2021

Patterns and Predictors of Cognitive Function Among Virally Suppressed Women With HIV.

Front Neurol 2021 11;12:604984. Epub 2021 Feb 11.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Cognitive impairment remains frequent and heterogeneous in presentation and severity among virally suppressed (VS) women with HIV (WWH). We identified cognitive profiles among 929 VS-WWH and 717 HIV-uninfected women from 11 Women's Interagency HIV Study sites at their first neuropsychological (NP) test battery completion comprised of: Hopkins Verbal Learning Test-Revised, Trail Making, Symbol Digit Modalities, Grooved Pegboard, Stroop, Letter/Animal Fluency, and Letter-Number Sequencing. Using 17 NP performance metrics (T-scores), we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores and clustering those nodes. Among VS-WWH, nine clusters were identified (entropy = 0.990) with four having average T-scores ≥45 for all metrics and thus combined into an "unimpaired" profile ( = 311). Impaired profiles consisted of weaknesses in: (1) sequencing (; = 129), (2) speed (; = 144), (3) learning + recognition (; = 137), (4) learning + memory (; = 86), and (5) learning + processing speed + attention + executive function (; = 122). Sociodemographic, behavioral, and clinical variables differentiated profile membership using Random Forest models. The top 10 variables distinguishing the combined impaired vs. unimpaired profiles were: clinic site, age, education, race, illicit substance use, current and nadir CD4 count, duration of effective antiretrovirals, and protease inhibitor use. Additional variables differentiating each impaired from unimpaired profile included: depression, stress-symptoms, income (); depression, employment (); depression, integrase inhibitor (INSTI) use (); employment, INSTI use, income, atazanavir use, non-ART medications with anticholinergic properties (); and marijuana use (). Findings highlight consideration of NP profile heterogeneity and potential modifiable factors contributing to impaired profiles.
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http://dx.doi.org/10.3389/fneur.2021.604984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928382PMC
February 2021

Longitudinal 5-year prediction of cognitive impairment among men with HIV disease.

AIDS 2021 05;35(6):889-898

Department of Psychiatry.

Background: Although combination antiretroviral therapy reduced the prevalence of HIV-associated dementia, milder syndromes persist. Our goals were to predict cognitive impairment of the Multicenter AIDS Cohort Study (MACS) participants 5 years ahead and from a large pool of factors, select the ones that mostly contributed to our predictions.

Design: Longitudinal, natural and treated history of HIV infection among MSM.

Methods: The MACS is a longitudinal study of the natural and treated history of HIV disease in MSM; the neuropsychological substudy aims to characterize cognitive disorders in men with HIV disease.

Results: We modeled on an annual basis the risk of cognitive impairment 5 years in the future. We were able to predict cognitive impairment at individual level with high precision and overperform default methods. We found that while a diagnosis of AIDS is a critical risk factor, HIV infection per se does not necessarily convey additional risk. Other infectious processes, most notably hepatitis B and C, are independently associated with increased risk of impairment. The relative importance of an AIDS diagnosis diminished across calendar time.

Conclusion: Our prediction models are a powerful tool to help clinicians address dementia in early stages for MACS paticipants. The strongest predictors of future cognitive impairment included the presence of clinical AIDS and hepatitis B or C infection. The fact that the pattern of predictive power differs by calendar year suggests a clinically critical change to the face of the epidemic.
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http://dx.doi.org/10.1097/QAD.0000000000002827DOI Listing
May 2021

Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV.

Menopause 2021 01 11;28(4):360-368. Epub 2021 Jan 11.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Objective: To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH).

Methods: A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean).

Results: Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%.

Conclusions: Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment.
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http://dx.doi.org/10.1097/GME.0000000000001725DOI Listing
January 2021

Evaluation of a screening tool for the identification of neurological disorders in rural Uganda.

J Neurol Sci 2021 Feb 24;421:117273. Epub 2020 Dec 24.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, University Teaching Hospital, Lusaka, Zambia. Electronic address:

Background: Neurological disorders are common in sub-Saharan African, but accurate neuroepidemiologic data are lacking from the region. We assessed a neuroepidemiological screening tool in a rural Ugandan cohort with high HIV prevalence.

Methods: Participants were recruited from the Rakai Neurology Study in rural Rakai District, Uganda. A nurse administered the tool and a sociodemographic survey. 100 participants returned for validation examinations by a neurologist (validation cohort). The diagnostic utility and validity of the instrument were calculated and characteristics of those with and without neurological disorders compared.

Results: The tool was administered to 392 participants, 48% female, 33% people with HIV, average age 35.1 ± 8.5 years. 33% of the study cohort screened positive for neurologic disorders. These participants were older [mean (SD): 38.3 (9.7) vs. 33.5 (7.1) years, p < 0.001], had a lower Karnofsky score [89.8 (8.4) vs. 93.9 (7.5), p < 0.001] and had a lower body mass index [21.8 (3.3) vs. 22.8 (3.7), p = 0.007] than those who screened negative. Amongst the validation cohort, 54% had a neurological abnormality of which 46% were symptomatic. The tool was 57% sensitive and 74% specific for detecting any neurological abnormality and 80% sensitive and 69% specific for symptomatic abnormalities.

Conclusions: We found a lower sensitivity and similar specificity for the screening tool compared with two previous studies. The lower validity in this study was likely due in part to the high percentage of asymptomatic neurological abnormalities detected. This screening tool will require further refinement and cultural contextualization before it can be widely implemented across new populations.
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http://dx.doi.org/10.1016/j.jns.2020.117273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914201PMC
February 2021

Plasma Lipidomic Profiles and Risk of Diabetes: 2 Prospective Cohorts of HIV-Infected and HIV-Uninfected Individuals.

J Clin Endocrinol Metab 2021 03;106(4):999-1010

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Objectives: Antiretroviral therapy (ART) use is associated with disrupted lipid and glucose metabolism in people with HIV infection. We aimed to identify plasma lipid species associated with risk of diabetes in the context of HIV infection.

Research Design And Methods: We profiled 211 plasma lipid species in 491 HIV-infected and 203 HIV-uninfected participants aged 35 to 55 years from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Cox proportional hazards model was used to examine associations between baseline lipid species and incident diabetes (166 diabetes cases were identified during a median follow-up of 12.6 years).

Results: We identified 11 lipid species, representing independent signals for 8 lipid classes/subclasses, associated with risk of diabetes (P < 0.05 after FDR correction). After adjustment for multiple covariates, cholesteryl ester (CE) (22:4), lysophosphatidylcholine (LPC) (18:2), phosphatidylcholine (PC) (36:4), phosphatidylcholine plasmalogen (34:3), and phosphatidylethanolamine (PE) (38:2) were associated with decreased risk of diabetes (HRs = 0.70 to 0.82 per SD increment), while diacylglycerol (32:0), LPC (14:0), PC (38:3), PE (36:1), and triacylglycerol (50:1) were associated with increased risk of diabetes (HRs = 1.26 to 1.56 per SD increment). HIV serostatus did not modify any lipid-diabetes associations; however, most of these lipid species were positively associated with HIV and/or ART use, including 3 diabetes-decreased ( CE [22:4], LPC [18:2], PE [38:2]) and all 5 diabetes-increased lipid species.

Conclusions: This study identified multiple plasma lipid species associated with incident diabetes. Regardless of the directions of their associations with diabetes, most diabetes-associated lipid species were elevated in ART-treated people with HIV infection. This suggests a complex role of lipids in the link between ART and diabetes in HIV infection.
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http://dx.doi.org/10.1210/clinem/dgab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993589PMC
March 2021

Integrase Strand Transfer Inhibitor Start or Switch Impacts Learning in Women With HIV.

J Acquir Immune Defic Syndr 2021 04;86(5):593-599

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH).

Setting: Women's Interagency HIV Study, a multisite, prospective, cohort study.

Methods: WWH who started or switched to INSTI-based antiretroviral therapy (ART) and completed neuropsychological testing and the Center for Epidemiological Studies-Depression (CES-D) scale before and after INSTI start/switch were included in the analyses. Primary outcomes were demographically corrected cognitive domain T-scores. Linear mixed-effects models adjusted for relevant covariates were used to examine effects of start/switch of any INSTI and individual INSTI drugs on cognition and CES-D scores.

Results: Six hundred thirty-nine WWH, median age 49 (interquartile range 12) years, 66% Black non-Hispanic, had neuropsychological and CES-D scale data before and after INSTI start/switch. Although 14% started INSTI-based ART, the remainder switched to INSTI-based ART from another regimen. Overall, any INSTI use was associated with poorer learning post-INSTI. Specifically, use of dolutegravir and elvitegravir, but not raltegravir, was associated with poorer learning. In analyses restricted to INSTI switch, any INSTI use, and dolutegravir use, was associated with poorer learning. Among those switching from a PI-based regimen, INSTIs overall and dolutegravir remained associated with poorer learning; switching from a nonnucleoside reverse transcriptase inhibitor to dolutegravir was also associated with poorer learning. INSTI start/switch was not related to depressive symptom changes.

Conclusions: INSTI use was associated with poorer learning among WWH. These changes were mainly observed in elvitegravir and dolutegravir users, indicating that the impact of INSTI on cognition in WWH may not be a class effect.
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http://dx.doi.org/10.1097/QAI.0000000000002608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319920PMC
April 2021

Long-term consequences of interpersonal violence experiences on treatment engagement and health status in people living with HIV.

AIDS 2021 04;35(5):801-809

Department of Psychiatry.

Objective: To examine the impact of previous interpersonal violence (IPersV) experiences on long-term healthcare engagement and health outcomes in a large Canadian HIV-cohort.

Design: People living with HIV (PLHIV) were screened for IPersV, and their healthcare outcomes over the nine subsequent years were analyzed.

Methods: A total of 1064 PLHIV were screened for past and present IPersV experiences through semistructured interviews. Follow-up included core treatment engagement (e.g. clinic visits) and health-status variables (HIV viral load, CD4+ T-cell count, mortality, comorbidities), analyzed descriptively and with longitudinal Cox regressions.

Results: At intake, 385 (36%) PLHIV reported past or present IPersV including childhood (n = 224, 21%) or adulthood experiences (n = 161, 15%) and were offered conventional social work support. Over 9 years, individuals with any IPersV experiences were 36% more likely to discontinue care, 81% more likely to experience viremia, 47% more likely to experience a drop in CD4+ cell counts below 200/μl, and 65% more likely to die compared with patients not reporting IPersV (P < 0.05). Outcomes were similar when adjusted for sociodemographic factors. Childhood IPersV in particular was linked to several of the outcomes, with higher rates of discontinuation of care, viremia, and mortality related to mental health/addiction or HIV-related complications.

Conclusion: IPersV is associated with an increased risk over time of healthcare discontinuation, poorer long-term HIV-related health outcomes, and increased mortality, especially for patients victimized in childhood. Apart from targeted IPersV screening to initiate conventional supports (e.g. through social work), increased efforts to engage vulnerable populations in their long-term care seems warranted.
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http://dx.doi.org/10.1097/QAD.0000000000002798DOI Listing
April 2021

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda.

Brain Behav Immun 2021 03 24;93:111-118. Epub 2020 Dec 24.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.
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http://dx.doi.org/10.1016/j.bbi.2020.12.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023502PMC
March 2021

Sex Differences in the Patterns and Predictors of Cognitive Function in HIV.

Front Neurol 2020 23;11:551921. Epub 2020 Nov 23.

Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.

Despite advancements in antiretroviral therapy, mild cognitive deficits persist in nearly half of people with HIV (PWH). The profile of impairment in HIV is highly variable with deficits observed in a range of cognitive domains. Despite evidence of greater cognitive impairment among women with HIV (WWH) vs. men with HIV (MWH), it is unclear how MWH and WWH differ in the type of cognitive impairment and in risk factors associated with cognitive impairment profiles. In a large and well-characterized sample of PWH, we used machine learning to identify profiles of cognitive functioning and their associated factors overall and within sex. Participants included 1,666 PWH (201 WWH; 1,465 MMH) from the HIV Neurobehavioral Research Program who completed a neuropsychological test battery at their baseline visits. Using demographically-adjusted T-scores from 13 test outcomes assessing motor skills, executive functioning, attention/working memory, episodic learning and memory, verbal fluency, and processing speed, we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores (MCLUST R package). Random forest models were used to determine how sociodemographic (e.g., age, education), clinical (e.g., depressive symptoms, substance use disorder), and biological (e.g., HIV disease characteristics) factors differentially related to membership within a cognitive profile. All analyses were repeated within sex. Three cognitive profiles were identified overall and within each sex. Overall and within MWH, there were unimpaired and global weakness profiles. The third profile in the total sample demonstrated relatively weak auditory attention whereas in MWH showed relative strengths in attention and processing speed. Conversely, there was no unimpaired profile among WWH. Rather, WWH demonstrated separate profiles reflecting weakness in motor skills, a relative weakness in learning and delayed recall, and global weaknesses with spared recognition memory. Despite different cognitive profiles by sex, the most discriminative factors were similar between men and women and included reading level (cognitive reserve), current and nadir CD4 count, plasma HIV viral load, duration of HIV disease, age, depressive symptoms, and race/ethnicity. Findings fill a knowledge gap concerning sex differences in cognitive impairment in PWH and inform personalized risk reduction and therapeutic strategies.
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http://dx.doi.org/10.3389/fneur.2020.551921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732436PMC
November 2020

Longitudinal multivariate normative comparisons.

Stat Med 2021 03 9;40(6):1440-1452. Epub 2020 Dec 9.

Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Motivated by the Multicenter AIDS Cohort Study (MACS), we develop classification procedures for cognitive impairment based on longitudinal measures. To control family-wise error, we adapt the cross-sectional multivariate normative comparisons (MNC) method to the longitudinal setting. The cross-sectional MNC was proposed to control family-wise error by measuring the distance between multiple domain scores of a participant and the norms of healthy controls and specifically accounting for intercorrelations among all domain scores. However, in a longitudinal setting where domain scores are recorded multiple times, applying the cross-sectional MNC at each visit will still have inflated family-wise error rate due to multiple testing over repeated visits. Thus, we propose longitudinal MNC procedures that are constructed based on multivariate mixed effects models. A test procedure is adapted from the cross-sectional MNC to classify impairment on longitudinal multivariate normal data. Meanwhile, a permutation procedure is proposed to handle skewed data. Through simulations we show that our methods can effectively control family-wise error at a predetermined level. A dataset from a neuropsychological substudy of the MACS is used to illustrate the applications of our proposed classification procedures.
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http://dx.doi.org/10.1002/sim.8850DOI Listing
March 2021

Weight and Body Mass Index Change After Switching to Integrase Inhibitors or Tenofovir Alafenamide Among Women Living with HIV.

AIDS Res Hum Retroviruses 2021 06 12;37(6):461-467. Epub 2021 Jan 12.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Weight and body mass index (BMI) change was assessed among women after switch to integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF). From 2006 to 2019, 1,458 women living with HIV enrolled in the Women's Interagency HIV Study and on antiretroviral therapy (ART) with ≥1 study visit before and after switching to INSTIs and/or TAF were included. Weight and BMI were compared pre- and postswitch to INSTI (by class and type) and/or TAF using multivariable linear mixed effects models; all models were also stratified by preswitch presence or absence of obesity (BMI ≥30 vs. <30 kg/m). Mean age preswitch was 47 ± 6 years, 64% were black, mean CD4 = 475 ± 201 cells/mm, 56% had HIV RNA <200 copies/mL, 36% switched to TAF but not INSTI, 60% to INSTI but not TAF, and 3.5% to TAF+INSTI. Time from pre- to postswitch was 12.8 ± 11.8 months. The INSTI-only group but not TAF groups had small but significant increases in weight and BMI: mean 79.2-80.6 kg and 30.2-30.7 kg/m, s < .001, respectively, with congruent findings by INSTI type (s ≤ .01). In stratified (preswitch BMI) analyses, only nonobese subgroups experienced increases in weight and BMI across all ART treatment groups (s < .05). Significant, although small-to-medium, increases in weight and BMI occurred among nonobese women who switched to INSTIs and/or TAF over short follow-up. Given long-term health consequences of obesity particularly as a low-grade inflammatory condition, identifying women at highest risk of ART-associated weight gain is imperative.
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http://dx.doi.org/10.1089/AID.2020.0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213005PMC
June 2021

Neural dynamics of attention in HIV: A cognitive aging phenotype?

EBioMedicine 2020 Dec 10;62:103114. Epub 2020 Nov 10.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD USA; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD USA. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2020.103114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658472PMC
December 2020

Factors Predicting Detrimental Change in Declarative Memory Among Women With HIV: A Study of Heterogeneity in Cognition.

Front Psychol 2020 15;11:548521. Epub 2020 Oct 15.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Objective: Statistical techniques used to study cognitive function in HIV typically yield normative estimates and can mask the heterogeneity in cognitive trajectories over time. We applied a novel statistical approach to identify clusters of individuals with distinct patterns of change in declarative memory in HIV-seropositive (HIV+) and HIV-seronegative (HIV-) women.

Methods: 1731 women from the Women's Interagency HIV Study, a multi-center, prospective cohort study, completed the Hopkins Verbal Learning Test-Revised (HLVT-R) at >2 visits. To derive subgroups with similar patterns of decline by HIV-serostatus, we used a mixed-effects framework that modeled the trajectory of multiple declarative memory outcomes over time, while simultaneously clustering individuals.

Results: Of the 1731 participants, 1149 were HIV+ (70% Black/African American [AA]; 30% White/Other [W/O]) and 582 were HIV- (68% AA; 32% W/O). Race stratification was necessary to optimize clustering. Among HIV+AA's, four subgroups emerged: a subgroup with minimal decline, two with accelerated decline, and one with stable but low performance. In HIV- AA, three subgroups emerged: one with minimal decline and two with accelerated decline. In multivariable-adjusted models among HIV+, individuals with accelerated decline were less educated ( < 0.001) and more likely to have a history of depression ( < 0.001) versus those with minimal decline. Similar subgroups were identified in W/O HIV+ and W/O HIV- participants.

Conclusion: We identified clinically meaningful subgroups of women with distinct phenotypes of declarative memory decline, which depend on race and HIV-serostatus using a data driven approach. Identification of underlying mechanisms and risk factors contributing to the observed differences are warranted. More broadly our modeling approach could be other populations to identify risk factors for accelerated cognitive decline and to personalize interventions.
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http://dx.doi.org/10.3389/fpsyg.2020.548521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594511PMC
October 2020

Physiologic vasomotor symptoms are associated with verbal memory dysfunction in breast cancer survivors.

Menopause 2020 11;27(11):1209-1219

Department of Psychology, University of Illinois, Chicago, IL.

Objective: Vasomotor symptoms (VMS), sleep disturbance, and cognitive complaints are common among women with a history of breast cancer and contribute to decreased quality of life. Studies in healthy women showed an association between verbal memory performance and physiologic VMS measured with ambulatory skin conductance monitors but not with VMS by self-report. We hypothesized that we would find a similar association in women with breast cancer.

Methods: Participants included 30 female breast cancer survivors (mean age 52.7 y; 26.7% African-American) with moderate-to-severe VMS enrolled in a larger clinical trial of a nonhormonal intervention for VMS. At baseline, participants completed assessments of physiologic VMS, actigraphy-based assessments of sleep, questionnaires about mood, and two tests of verbal memory - Logical Memory (LM) and the California Verbal Learning Test (CVLT). Using baseline data, we conducted multivariate regression analyses to examine the association between VMS and memory, controlling for sleep and other factors.

Results: On average, women reported 46% of total physiologic VMS. A higher frequency of physiologic VMS - but not reported VMS - was significantly associated with lower scores on the California Verbal Learning Test short-delay free recall (r[28] = -0.41, P = 0.03), long-delay free recall (r[28] = -0.42, P = 0.03), and total clustering, (r[28] = -0.39, P = 0.04). These associations were independent of sleep, mood, and other factors.

Conclusions: Independent of their effect on sleep, VMS may be a modifiable contributor to memory difficulties in women with breast cancer. These findings underscore the importance of objective measurement of VMS in cognitive studies. : Video Summary:http://links.lww.com/MENO/A623.
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http://dx.doi.org/10.1097/GME.0000000000001608DOI Listing
November 2020

Multivariate relationships between peripheral inflammatory marker subtypes and cognitive and brain structural measures in psychosis.

Mol Psychiatry 2021 Jul 15;26(7):3430-3443. Epub 2020 Oct 15.

Department of Experimental and Clinical Pharmacology and Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.

Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n = 79; Psychotic Bipolar disorder, n = 61) and matched healthy controls (HC, n = 60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.
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http://dx.doi.org/10.1038/s41380-020-00914-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046847PMC
July 2021
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