An Umbrella Review of Self-Management Interventions for Health Conditions With Symptom Overlap With Traumatic Brain Injury.

OBJECTIVE: To synthesize evidence for the effectiveness of self-management interventions for chronic health conditions that have symptom overlap with traumatic brain injury (TBI) in order to extract recommendations for self-management intervention in persons with TBI. DESIGN: An umbrella review of existing systematic reviews and/or meta-analyses of randomized controlled trials or nonrandomized studies targeting self-management of chronic conditions and specific outcomes relevant to persons with TBI. METHOD: A comprehensive literature search of 5 databases was conducted using PRISMA guidelines. Two independent reviewers conducted screening and data extraction using the Covidence web-based review platform. Quality assessment was conducted using criteria adapted from the Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2). RESULTS: A total of 26 reviews met the inclusion criteria, covering a range of chronic conditions and a range of outcomes. Seven reviews were of moderate or high quality and focused on self-management in persons with stroke, chronic pain, and psychiatric disorders with psychotic features. Self-management interventions were found to have positive effects on quality of life, self-efficacy, hope, reduction of disability, pain, relapse and rehospitalization rates, psychiatric symptoms, and occupational and social functioning. CONCLUSIONS: Findings are encouraging with regard to the effectiveness of self-management interventions in patients with symptoms similar to those of TBI. However, reviews did not address adaptation of self-management interventions for those with cognitive deficits or for populations with greater vulnerabilities, such as low education and older adults. Adaptations for TBI and its intersection with these special groups may be needed.

The application of Strategy-based Training to Enhance Memory (STEM) in multiple sclerosis: A pilot RCT.

New learning and memory (NLM) impairments are common in multiple sclerosis (MS), negatively impacting daily life. Few studies seek to remediate these deficits to improve everyday functioning. Self-generation, spaced learning and retrieval practice have been shown to improve NLM in healthy persons and have been incorporated into an 8-session treatment protocol, Strategy-based Training to Enhance Memory (STEM). STEM teaches participants about each of the techniques, how to apply them in daily life and provides practice. Participants are taught to restructure a memory-demanding situation to optimize self-generation, spaced learning and retrieval practice. This pilot double-blind, placebo-controlled, randomized clinical trial (RCT) tested the efficacy of STEM in 20 learning-impaired participants with clinically definite MS (9 treatment, 11 control). Significant treatment effects were noted on self-report measures of daily functioning (primary outcome). Objective neuropsychological testing approached significance, showing a medium-large effect on verbal NLM. Results suggest that STEM may improve everyday functioning in individuals with MS. A full-scale RCT is warranted to validate findings in a larger sample so that findings may be generalized to the broader MS community.

The Neural Mechanisms Underlying Processing Speed Deficits in Individuals Who Have Sustained a Spinal Cord Injury: A Pilot Study.

Our objective was to determine differences in brain activation during a processing-speed task in individuals with SCI compared to a group of age-matched healthy controls and to a group of older healthy controls. Ten individuals with cervical SCI (C3-C5), 10 age-matched healthy controls and 10 older healthy controls participated in a cross-sectional study in which performance on neuropsychological tests of processing speed and brain activation were the main outcome measures. The brain areas used by the individuals with SCI during the processing-speed task differed significantly from the age-matched healthy controls, but were similar to the older control cohort, and included activation in frontal, parietal and hippocampal areas. This suggests that individuals with SCI may compensate for processing-speed deficits by relying on brain regions that classically support control cognitive processes such as executive control and memory.

Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI.

STUDY DESIGN: Clinical trial. OBJECTIVES: Individuals with spinal cord injury (SCI) above T6 experience impaired descending cortical control of the autonomic nervous system, which predisposes them to hypotension. However, treatment of hypotension is uncommon in the SCI population because there are few safe and effective pharmacological options available. The primary aim of this investigation was to test the efficacy of a single dose of midodrine (10 mg), compared with placebo, to increase and normalize systolic blood pressure (SBP) between 110 and 120 mmHg during cognitive testing in hypotensive individuals with SCI. Secondary aims were to determine the effects of midodrine on cerebral blood flow velocity (CBFv) and global cognitive function. SETTING: United States clinical research laboratory. METHODS: Forty-one healthy hypotensive individuals with chronic (≥1-year post injury) SCI participated in this 2-day study. Seated SBP, CBFv, and cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo. RESULTS: Compared with placebo, midodrine increased SBP (4 ± 13 vs. 18 ± 24 mmHg, respectively; p < 0.05); however, responses varied widely with midodrine (-15.7 to +68.6 mmHg). Further, the proportion of SBP recordings within the normotensive range did not improve during cognitive testing with midodrine compared with placebo. Although higher SBP was associated with higher CBFv (p = 0.02), global cognitive function was not improved with midodrine. CONCLUSIONS: The findings indicate that midodrine increases SBP and may be beneficial in some hypotensive patients with SCI; however, large heterogeneity of responses to midodrine suggests careful monitoring of patients following administration. CLINICAL TRIALS REGISTRATION: NCT02307565.

Comparing learning performance on the open trial selective reminding test with the California verbal learning test II in traumatic brain injury.

Introduction: Learning and memory deficits are prevalent following moderate to severe traumatic brain injury (TBI), affecting between 54% and 84% of impacted individuals.Objective: The current study examined learning performance on two tests of verbal memory: the OT-SRT and the CVLT-II.Methods: Sixty-eight participants with TBI performed the OT-SRT and the CVLT-II on two different days. Additionally, all participants completed cognitive tests assessing processing speed, working memory and executive functions. By definition, all participants with TBI were identified as having impaired learning on the OT-SRT, however only 38 were also identified as impaired on the CVLT-II. The sample was thus divided into two groups, those who failed both tests (Fail-2) and those who failed only the OT-SRT (Fail-1).Results: The Failed-1 group showed significantly better performance in processing speed, working memory and executive functions compared to the Fail-2 group. On the CVLT-II, the Fail-1 group performed significantly better on the number of words recalled on trials 1 and 5 compared to the Fail-2 group. Both groups performed similarly the OT-SRT.Discussion: The CVLT-II and the OT-SRT are not equivalent tests and should not be used interchangeably.

Factors associated with the remission of insomnia after traumatic brain injury: a traumatic brain injury model systems study.

Objective: To examine the factors associated with the remission of insomnia by examining a sample of individuals who had insomnia within the first two years after traumatic brain injury (TBI) and assessing their status at a secondary time point.Design and Methods: Secondary data analysis from a multicenter longitudinal cohort study. A sample of 40 individuals meeting inclusion criteria completed a number of self-report scales measuring sleep/wake characteristics (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Insomnia Severity Index, Sleep Hygiene Index), fatigue and depression (Multidimensional Assessment of Fatigue, Patient Health Questionnaire-9), and community participation (Participation Assessment with Recombined Tools-Objective). One cohort was followed at 1 and 2 years post-injury (n = 19) while a second cohort was followed at 2 and 5 years post-injury (n = 21).Results: Remission of insomnia was noted in 60% of the sample. Those with persistent insomnia had significantly higher levels of fatigue and depression at their final follow-up and poorer sleep hygiene across both follow-up time-points. A trend toward reduced community participation among those with persistent insomnia was also found.Conclusion: Individuals with persistent post-TBI insomnia had poorer psychosocial outcomes. The chronicity of post-TBI insomnia may be associated with sleep-related behaviors that serve as perpetuating factors.

Beyond cognitive dysfunction: Relevance of ecological validity of neuropsychological tests in multiple sclerosis.

In neurological diseases such as multiple sclerosis (MS), a neuropsychological assessment is often requested to assist clinicians in evaluating the role of cognition in a patient's level of everyday functioning. To be effective in this charge, it is assumed that performance on neuropsychological tests is related to how a person may function in everyday life, and the question is often asked: "Are neuropsychological tests ecologically valid?" In this review, we synthesize the literature that examines the use of neuropsychological tests to assess functioning across a variety of everyday functioning domains in MS (i.e. driving, employment, instrumental activities of daily living (IADLs)). However, we critically examine the usefulness of asking this broad question regarding ecological validity, given the psychometric and conceptual pitfalls it may yield. While many neuropsychological tests may be generally considered "ecologically valid" in MS, it is much more helpful to specify for whom, under what circumstances, and to what degree.

Time-Based Prospective Memory Is Associated with Functional Performance in Persons with MS.

OBJECTIVE: Persons with multiple sclerosis (MS) often report prospective memory (PM) failures that directly impact their everyday life. However, it is not known whether PM deficits confer an increased risk of poorer everyday functioning. The aims of this study were to: (1) compare time- (Time-PM) and event-based PM (Event-PM) performance between persons with MS and healthy controls (HCs), (2) examine the neuropsychological correlates of PM in MS, and (3) examine the relationship between PM and everyday functioning in MS. METHOD: A between-subjects design was used to examine 30 adults with MS and 30 community-dwelling HC. Participants were administered the Memory for Intentions Screening Test (MIST) to assess PM skills, the Actual Reality™ (AR) to assess everyday functioning, and a battery of cognitive tests. RESULTS: The MS group performed significantly worse on Time-PM compared to HC but not on Event-PM tasks. While both Time-PM and Event-PM subscales were correlated with retrospective learning and memory, the MIST Time-PM subscale was correlated with executive functions. Significant correlations were observed between AR and the MIST Time-PM, but not Event-PM, subscales. CONCLUSIONS: The results highlight the role of executive functions on Time-PM. Furthermore, significant relationships with AR extend the ecological validity of the MIST to MS populations.

Physical, Cognitive, and Psychosocial Characteristics Associated With Mortality in Chronic TBI Survivors: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To compare a group of individuals who died more than 1 year posttraumatic brain injury (TBI) with a matched group of survivors and to identify physical function, cognitive function, and/or psychosocial function variables associated with mortality. DESIGN: Secondary analysis of data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities and community follow-up. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM), Disability Rating Scale, Participation Assessment with Recombined Tools Objective, Extended Glasgow Outcome Scale, Satisfaction With Life Scale. RESULTS: Individuals who died were distinguishable from their surviving counterparts. They demonstrated significantly poorer global functioning on all physical, cognitive, and psychosocial functioning variables at their most recent study follow-up visit prior to death. FIM Motor demonstrated the largest difference between survival groups, suggesting that independence in mobility may be particularly indicative of likelihood of longer-term survival. CONCLUSIONS: These findings may inform continued research to elucidate functional characteristics of individuals postchronic TBI prior to their death and to identify opportunities for prevention of accelerated death and interventions to improve health, longevity, and quality of life.

Time estimation and production in HIV-associated neurocognitive disorders (HAND).

The ability to accurately perceive the passage of time relies on several neurocognitive abilities, including attention, memory, and executive functions, which are domains commonly affected in persons living with HIV disease. The current study examined time estimation and production and their neurocognitive correlates in a sample of 53 HIV+ individuals with HIV-associated neurocognitive disorders (HAND), 120 HIV+ individuals without HAND, and 113 HIV- individuals. Results revealed a moderate main effect of HAND on time estimation and a trend-level effect on time production, but no interaction between HAND and time interval duration. Correlational analyses revealed that time estimation in the HIV+ group was associated with attention, episodic memory and time-based prospective memory. Findings indicate that individuals with HAND evidence deficits in time interval judgment suggestive of failures in basic attentional and memory processes.

Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection.

The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naive adults with median duration of infection of 75 days relative to a sample of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States, a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly fivefold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, the results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use.

Cognitive neurorehabilitation of HIV-associated neurocognitive disorders: a qualitative review and call to action.

Despite significant advances in the virologic management of HIV infection over the last two decades, effective treatments for HIV-associated neurocognitive disorders (HAND) remain elusive. While pharmacological interventions have yielded some success in improving neurocognitive outcomes in HIV, there is a dearth of rigorous studies examining the efficacy of cognitive rehabilitation for remediating HIV-associated neurocognitive impairment. This qualitative review summarizes and critiques the emerging literature on cognitive and behavioral treatments for HAND, which provides many reasons for optimism, but also has major limitations that underscore the scope of the work that lies ahead. Considering the notable real-world consequences of HAND, the development, validation, and clinical deployment of cognitive neurorehabilitation interventions tailored to the needs of persons living with HIV infection is a priority for clinical neuroAIDS investigators. In describing potential future directions for this endeavor, particular attention was paid to the application of cognitive neuropsychological principles in developing theory-driven approaches to managing HAND, improving everyday functioning, and enhancing HIV health outcomes.

Feasibility of remotely delivered and supported aerobic walking exercise training for cognitive processing speed impairment in fully-ambulatory persons with multiple sclerosis.

PURPOSE: The current pilot, single-blind, randomized controlled trial (RCT) examined the feasibility of remotely-delivered and supported aerobic walking exercise training compared with an active control condition on cognitive processing speed (CPS) in 19 fully-ambulatory persons with multiple sclerosis (pwMS) who were pre-screened for impaired CPS. METHODS: Feasibility was assessed in the domains of process (e.g., recruitment), resource (e.g., monetary costs), management (e.g., time requirements), and scientific outcomes (i.e., treatment effect). Fully-ambulatory, but CPS-impaired pwMS were randomly assigned into either 16-weeks of home-based aerobic walking exercise or home-based stretching and range-of-motion activities. Both conditions involved delivery of informational newsletters and one-on-one, online video chats with a behavior coach. Participants across both conditions tracked their activity using highly accurate wearable motion sensors. Treatment-blinded assessors administered the Symbol Digit Modalities Test (SDMT) remotely before and after the 16-week study period. RESULTS: The study was cost-effective, accessible, and acceptable. The intervention further was safe. Adherence and compliance rates across both conditions exceeded 80%. There was an overall moderate effect for change in SDMT score between the conditions (d = 0.42). The intervention was associated with a 4.8-point improvement in SDMT scores (d = 0.70; 10% increase) compared with a 1-point improvement for the control condition (d = 0.09; 2% increase). CONCLUSIONS: This remotely-delivered and supported aerobic walking exercise training intervention was safe and feasible for fully-ambulatory, CPS-impaired pwMS. The pattern of results, including the promising effects on CPS, support the design and implementation of an appropriately-powered RCT on this approach for managing CPS impairment in a large MS sample.

Autonomic Cardiovascular Control, Psychological Well-Being, and Cognitive Performance in People With Spinal Cord Injury.

PURPOSE: To examine associations between parameters of psychological well-being, injury characteristics, cardiovascular autonomic nervous system (ANS) control, and cognitive performance in persons with spinal cord injury (SCI) compared with age-matched uninjured controls. This is an observational, cross-sectional study including a total of 94 participants (52 with SCI and 42 uninjured controls: UIC). Cardiovascular ANS responses were continuously monitored at rest and during administration of the Paced Auditory Serial Addition Test (PASAT). Self-report scores on the SCI-Quality of Life questionnaires are reported for depression, anxiety, fatigue, resilience, and positive affect. Participants with SCI performed significantly more poorly on the PASAT compared with the uninjured controls. Although not statistically significant, participants with SCI tended to report more psychological distress and less well-being than the uninjured controls. In addition, when compared with uninjured controls, the cardiovascular ANS responses to testing were significantly altered in participants with SCI; however, these responses to testing did not predict PASAT performance. Self-reported levels of anxiety were significantly related to PASAT score in the SCI group, but there was no significant relationship between PASAT and the other indices of SCI-Quality of Life. Future investigations should more closely examine the relationship among cardiovascular ANS impairments, psychological disorders, and cognitive dysfunction to better elucidate the underpinnings of these deficits and to guide interventions aimed at improving physiological, psychological, and cognitive health after SCI. Tetraplegia, paraplegia, blood pressure variability, cognitive, mood.

The effects of cognitive rehabilitation combined with aerobic exercise or stretching-and-toning on new learning and memory in persons with moderate-to-severe TBI: Protocol for a randomized controlled trial.

This paper describes the protocol for a Phase I/II, parallel-group, blinded randomized controlled trial that compares the effects of 12-weeks of combined learning and memory rehabilitation with either aerobic cycling exercise or stretching on cognitive, neuroimaging, and everyday life outcomes in 60 persons with moderate-to-severe traumatic brain injury (TBI) who demonstrate impairments in new learning. Briefly, participants will undergo baseline testing consisting of neuropsychological testing, neuroimaging, daily life measures, and cardiorespiratory fitness. Following baseline testing, participants will be randomized to one of 2 conditions (30 participants per condition) using concealed allocation. Participants will be masked as to the intent of the conditions. The conditions will both involve supervised administration of an enhanced, 8-week version of the Kessler Foundation modified Story Memory Technique, embedded within either 12-weeks of supervised and progressive aerobic cycling exercise training (experimental condition) or 12-weeks of supervised stretching-and-toning (active control condition). Following the 12-week intervention period, participants will complete the same measures as at baseline that will be administered by treatment-blinded assessors. The primary study outcome is new learning and memory impairment based on California Verbal Learning Test (CVLT)-III slope, the secondary outcomes include neuroimaging measures of hippocampal volume, activation, and connectivity, and the tertiary outcomes involve measures of daily living along with other cognitive outcomes. We further will collect baseline sociodemographic data for examining predictors of response heterogeneity. If successful, this trial will provide the first Class I evidence supporting combined memory rehabilitation and aerobic cycling exercise training for treating TBI-related new learning and memory impairment.

Altered prefronto-striato-parietal network response to mental rotation in HIV.

The present study used functional magnetic resonance imaging to examine the neural substrates of mental rotation in 11 individuals with HIV infection and 13 demographically similar HIV seronegative volunteers. Individuals with HIV showed increased brain response to mental rotation in prefrontal and posterior parietal cortices, striatum, and thalamus, with significant HIV by angle interactions emerging in the prefrontal cortex and caudate. Results indicate that HIV infection is associated with altered brain response to mental rotation in fronto-striato-parietal pathways, which may reflect compensatory strategies, recruitment of additional brain regions, and/or increased neuroenergetic demands during mental rotation needed to offset underlying HIV-associated neural injury.

Self-generation enhances verbal recall in individuals infected with HIV.

Despite the prevalence of HIV-associated episodic memory impairment and its adverse functional impact, there are no empirically validated cognitive rehabilitation strategies for HIV-infected persons. The present study examined the self-generation approach, which is theorized to enhance new learning by elaborating and deepening encoding. Participants included 54 HIV-infected and 46 seronegative individuals, who learned paired word associates in both self-generated and didactic encoding experimental conditions. Results revealed main effects of HIV serostatus and encoding condition, but no interaction. Planned comparisons showed that both groups recalled significantly more words learned in the self-generation condition, and that HIV+ individuals recalled fewer words overall compared to their seronegative counterparts at delayed recall. Importantly, HIV+ participants with clinical memory impairment evidenced similar benefits of self-generation compared to unimpaired HIV+ subjects. Self-generation strategies may improve verbal recall in individuals with HIV infection and may, therefore, be an appropriate and potentially effective cognitive rehabilitation tool in this population.

Aging, prospective memory, and health-related quality of life in HIV infection.

HIV infection and older age are each independently associated with lower health-related quality of life (HRQoL) and deficits in prospective memory (PM), which is a distinct aspect of cognition involving the ability to "remember to remember" to do something at a future occasion. The present study investigated associations between PM and HRQoL in 72 older (≥ 50 years) and 41 younger (≤ 40 years) HIV-infected adults. Self-reported PM complaints predicted HRQoL across the entire sample, but there was a significant interaction between performance-based PM and age group on HRQoL, such that lower time-based PM was associated with lower HRQoL only in the younger cohort. Within the younger group, time-based and self-reported PM significantly predicted mental HRQoL independent of other risk factors (e.g. depression). These findings suggest that PM plays a unique role in HRQoL outcomes among younger persons living with HIV infection and support the examination of other age-related factors (e.g. effective use of compensatory strategies) that may regulate the adverse impact of PM on everyday functioning.

Lower cognitive reserve among individuals with syndromic HIV-associated neurocognitive disorders (HAND).

HIV-seropositive individuals with low cognitive reserve are at high risk for developing HIV-associated neurocognitive disorders (HAND). The present study evaluated the hypothesis that cognitive reserve would also play a unique role in the expression of everyday functioning complications among those with HAND (i.e., syndromic versus subsyndromic impairment). Eighty-six individuals with HIV infection were evaluated; 53 individuals evidenced normal neurocognitive performance, 16 had subsyndromic HAND (i.e., asymptomatic neurocognitive impairment), and 17 were diagnosed with syndromic HAND based on a comprehensive neurobehavioral evaluation. Cognitive reserve represented a combined score including years of education, estimated verbal IQ, and highest occupational attainment. The groups were comparable (e.g. demographics), and the HAND groups had similar rates of global neurocognitive impairment. The syndromic HAND group evidenced lower reserve scores relative to both other groups, suggesting that individuals with lower reserve may be less able to effectively counteract their neurocognitive impairment to maintain independence in daily living activities than HIV-infected individuals with high cognitive reserve.

Semantic cueing improves category verbal fluency in persons living with HIV infection.

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in the era of combination antiretroviral therapies, but there are no validated psychological interventions aimed at improving cognitive outcomes. This study sought to determine the potential benefit of semantic cueing on category fluency deficits, which are prevalent in HIV and affect daily functioning. A group of 86 HIV-infected individuals and 87 demographically-matched seronegative participants were administered a standard (i.e., uncued) and a cued category fluency task. Results revealed significant improvements in cued versus uncued performance in HIV, particularly for persons with lower levels of education. The cueing benefit observed may inform rehabilitation efforts aimed at ameliorating HAND.