Mindfulness-Based Stress Reduction for Symptom Management in Older Individuals with HIV-Associated Neurocognitive Disorder.

The growing number of people aging with HIV represents a group vulnerable to the symptom burdens of HIV-associated neurocognitive disorder (HAND). Among younger groups, Mindfulness-Based Stress Reduction (MBSR) has been shown to help people living with HIV manage HIV-related and other life stress, and although there is some theoretical and empirical evidence that it may be effective among those with cognitive deficits, the approach has not been studied in older populations with HAND. Participants (n = 180) 55 years or older with HIV and cognitive impairment were randomly assigned to either an 8-week MBSR arm or a waitlist control. We assessed the impact of MBSR compared to a waitlist control on psychological outcomes [stress, anxiety, depression, and quality of life (QOL)] and cognitive metrics (e.g., speed of information processing, working memory, attention, impulsivity) measured at baseline, immediately post intervention (8 weeks) and one month later (16 weeks). Intent to treat analyses showed significant improvement in the MBSR group compared to control on symptoms of depression from baseline to 8 weeks, however, the difference was not sustained at 16 weeks. The MBSR group also showed improvement in perceived QOL from baseline to 16 weeks compared to the waitlist control group. Cognitive performance did not differ between the two treatment arms. MBSR shows promise as a tool to help alleviate the symptom burden of depression and low QOL in older individuals living with HAND and future work should address methods to better sustain the beneficial impact on depression and QOL.

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481.

CROI 2022: neurologic complications of HIV-1, SARS-CoV-2, and other pathogens.

The 2022 Conference on Retroviruses and Opportunistic Infections featured new and important findings about the neurologic complications of HIV-1, COVID-19, and other infections. Long-term analyses identified that cognitive decline over time, phenotypic aging, and stroke are associated with various comorbidities in people with HIV. Neuroimaging studies showed greater neuroinflammation, white matter damage, demyelination, and overall brain aging in people with chronic HIV infection. Childhood trauma and exposure to environmental pollutants contribute to these neuroimaging findings. Studies of blood and cerebrospinal fluid biomarkers showed that systemic inflammation, neurodegeneration, endothelial activation, oxidative stress, and iron dysregulation are associated with worse cognition in people with HIV. Some animal studies focused on myeloid cells of the central nervous system, but other animal and human studies showed that lymphoid cells also contribute to HIV neuropathogenesis. The deleterious central nervous system effects of polypharmacy and anticholinergic drugs in people with HIV were demonstrated. In contrast, a large randomized controlled trial showed that integrase strand transfer inhibitor therapy was not associated with neurotoxicity. Studies of cryptococcal meningitis demonstrated he cost-effectiveness of single high-dose liposomal amphotericin and the prognostic value of the cryptococcal antigen lateral flow assay. People hospitalized with COVID-19 had more anxiety over time after discharge. The SARS-CoV-2 nucleocapsid antigen is present in cerebrospinal fluid in the absence of viral RNA. Systemic inflammation, astrocyte activation, and tryptophan metabolism pathways are associated with post-COVID-19 neurologic syndromes. Whether these processes are independent or intertwined during HIV-1 and COVID-19 infections requires further study.

Mindfulness-based stress reduction for HIV-associated neurocognitive disorder: Rationale and protocol for a randomized controlled trial in older adults.

The symptom burden of HIV-associated neurocognitive disorder (HAND) is high among older individuals, and treatment options are limited. Mindfulness-based stress reduction (MBSR) has potential to improve neurocognitive performance, psychosocial wellbeing, and quality of life, but empirical studies in this growing vulnerable population are lacking. In this trial, participants (N = 180) age 55 and older who are living with HIV infection, are on combination antiretroviral therapy with suppressed viral loads, and yet continue to experience behavioral and cognitive symptoms of HAND, are randomized to MBSR or to a waitlist control arm that receives MBSR following a 16-week period of standard care. Primary outcomes (attention, executive function, stress, anxiety, depression, everyday functioning, quality of life) and potential mediators (affect, mindfulness) and moderators (social support, loneliness) are assessed at baseline and weeks 8, 16, and 48 in both groups, with an additional assessment at week 24 (post-MBSR) in the crossover control group. Assessments include self-report and objective measures (e.g., neuropsychological assessment, neurological exam, clinical labs). In addition, a subset of participants (n = 30 per group) are randomly selected to undergo fMRI to evaluate changes in functional connectivity networks and their relationship to changes in neuropsychological outcomes. Forthcoming findings from this randomized controlled trial have the potential to contribute to a growing public health need as the number of older adults with HAND is expected to rise.

Mindfulness, Education, and Exercise for age-related cognitive decline: Study protocol, pilot study results, and description of the baseline sample.

BACKGROUND/AIMS: Age-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such interventions. METHODS: Here, we describe the design of the Mindfulness, Education, and Exercise study, an 18-month randomized controlled trial that will assess the effect of two interventions-mindfulness training plus moderate-to-vigorous intensity exercise or moderate-to-vigorous intensity exercise alone-compared with a health education control group on cognitive function in older adults. An extensive battery of biobehavioral assessments will be used to understand the mechanisms of cognitive remediation, by using structural and resting state functional magnetic resonance imaging, insulin sensitivity, inflammation, and metabolic and behavioral assessments. RESULTS: We provide the results from a preliminary study (n = 29) of non-randomized pilot participants who received both the exercise and Mindfulness-Based Stress Reduction interventions. We also provide details on the recruitment and baseline characteristics of the randomized controlled trial sample (n = 585). CONCLUSION: When complete, the Mindfulness, Education, and Exercise study will inform the research community on the efficacy of these widely available interventions improve cognitive functioning in older adults.