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Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

ABSTRACT: To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment.We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily), lithium (400 mg twice daily, titrated progressively), or remained in a control group (no new medication). The primary efficacy endpoint was change in a global cognitive score (NPZ-7). Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results.Seventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]): rivastigmine, 0.35 (0.14); lithium, 0.25 (0.40); control, 0.20 (0.44) (p = 0.78). The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48): rivastigmine, -0.47 (0.22) vs -0.11 (0.29), p = 0.06; lithium, -0.50 (0.40) vs -0.26 (0.21), p = 0.22; control, -0.52 (0.34) vs -0.32 (0.52), p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control): information processing speed, 0.35 (0.64) vs -0.13 (0.25), p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33) vs 0.03 (0.74), p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41%) individuals dropped out of the study: 2 (20%) were due to medication-related effects in the rivastigmine group and 4 (36%) in the lithium group. No severe adverse events were reported.The results from this small randomized trial indicate that transdermal rivastigmine did not provide significant cognitive benefits in people with HAND on stable antiretroviral therapy, even though positive trends were found in specific cognitive domains. Relevant tolerability issues were not observed.

SUBMITTER: Munoz-Moreno JA

PROVIDER: S-EPMC5576750 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

Muñoz-Moreno Jose A JA Prats Anna A Moltó José J Garolera Maite M Pérez-Álvarez Núria N Díez-Quevedo Crisanto C Miranda Cristina C Fumaz Carmina R CR Ferrer Maria J MJ Clotet Bonaventura B

PloS one 20170830 8

<h4>Objective</h4>To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment.<h4>Methods</h4>We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily), lithium (400 mg twice daily, titrated progressively), or remained in a control ...[more]

PMID: 28854283

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Project description:OBJECTIVE:We determined whether there are sex differences in the prevalence and profile of HIV-associated neurocognitive impairment, and whether sex moderates the effect of HIV-serostatus on neurocognitive impairment among HIV-positive and HIV-negative individuals. Secondarily, we assessed whether differences were explained by greater biopsychosocial risk factors in HIV-positive women. DESIGN:An observational cohort study. METHODS:Analyses included 1361 HIV-positive (204 women) and 702 HIV-negative (214 women) (ages?=?18-79 years) participants from the UCSD HIV Neurobehavioral Research Program. Demographically corrected standardized T-scores from 15 neuropsychological tests were used to calculate domain-specific and global deficit scores (GDS). GDS at least 0.5 defined neurocognitive impairment. Biopsychosocial risk factors included low education, low reading level (education quality), lifetime substance use disorders, depressed mood (clinically significant depressive symptoms and/or current major depressive disorder) and a cumulative syndemic count (sum of biopsychosocial risk factors, range?=?0-4). Race-stratified analyses were conducted. Analyses were adjusted for relevant demographic and clinical factors. RESULTS:HIV-associated neurocognitive impairment was more prevalent in women versus men; however, the difference was eliminated after adjustment for reading level. In sex-stratified logistic regressions, the association between HIV-seropositivity and higher likelihood of neurocognitive impairment was stronger in women versus men; however, the association was attenuated in women, but not men, after adjusting for reading level. These results in the overall sample were specific to blacks. Sex differences in the profile of HIV-associated neurocognitive impairment varied by race. CONCLUSION:Women, particularly black women, were most at-risk for HIV-associated neurocognitive impairment. Higher rates of HIV-associated neurocognitive impairment in women versus men may reflect differences in educational quality.

Project description:IntroductionThe associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures.MethodsThe study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD.ResultsAmong 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification.ConclusionIn exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.

Project description:ObjectiveTo assess the effectiveness of the selegiline transdermal system (STS) in reversing HIV-induced metabolic brain injury (as measured by proton magnetic resonance spectroscopy [MRS]) and in decreasing oxidative stress, measured by CSF protein carbonyl concentration.MethodsSixty-two subjects with HIV-associated cognitive impairment were coenrolled in a 24-week placebo-controlled study (AIDS Clinical Trial Group protocol A5090) and were randomly assigned to receive STS 3 mg/24 h, STS 6 mg/24 h, or matching placebo. Cognitive performance was evaluated using the neuropsychological z score (NPZ)-8 and NPZ-6, as well as cognitive domain scores. Subjects underwent proton MRS at study entry and weeks 12 and 24. CSF protein carbonyl was measured at baseline and week 24.ResultsA slight increase in N-acetyl aspartate/creatine from baseline to week 24 was found in the basal ganglia (p = 0.023) and centrum semiovale (p = 0.072) of the placebo group compared with the STS groups; however, there were no significant changes when the absolute metabolite concentrations were analyzed. The levels of choline/creatine in the midfrontal cortex were also significantly higher during the week 12 visit in the combined STS groups. This persisted to the week 24 visit (p = 0.002). Evaluation of the change in NPZ-8, NPZ-6, and cognitive domain scores from baseline to weeks 12 and 24 revealed no significant differences between treatment arms. Protein carbonyl analysis revealed no significant changes among the groups.ConclusionIn this 24-week study, the selegiline transdermal system (STS) had no effect on either magnetic resonance spectroscopy (MRS) metabolites or oxidative stress, as measured by CSF protein carbonyl concentration. The lack of effect on these biomarkers is also reflected in the lack of cognitive improvement in the STS groups compared to placebo.Level of evidenceThis study provides Class II evidence that STS had no effect on either MRS metabolites or oxidative stress, as measured by CSF protein carbonyl concentration over a period of 24 weeks.

Project description:BackgroundTranscranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer's disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group.MethodsTwenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3).ResultsSignificant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word (p = 0.047)], innovation [TOSL (p = 0.01)] and on episodic memory [TOSL (p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm3) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort (p = 0.033)] and category fluency [COWAT (p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT (p = 0.009)].ConclusionOne intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

Dataset Information

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

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Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

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