Effect of a Home-Based Exercise Program on Indices of Physical Function and Quality of Life in Elderly Maintenance Hemodialysis Patients.

BACKGROUND: Patients on maintenance hemodialysis (MHD) exhibit muscle wasting and impaired physical function which can be reversed with regular exercise, but accessibility to exercise programs for this unique population is lacking. We assessed the efficacy of a home-based exercise program on a broad range of indices of physical function, quality of life (QoL), and cognitive decline in patients with MHD. DESIGN AND METHODS: Twenty-eight MHD patients, mean age 66 ± 7 years, were randomized to a 12-week home-based, case-managed aerobic and resistance exercise program or to usual care (13 exercise and 15 usual care). Comparisons were made for peak VO2, ventilatory inefficiency, 6-min walk test (6MWT), 1-min sit-to-stand (1STS), muscle strength, body composition, QoL, and cognitive measures. RESULTS: Peak VO2 improved significantly in the exercise group (p = 0.01 between groups); exercise time improved by 41 and 36% at the ventilatory threshold and peak exercise, respectively (p < 0.01 between groups), but there were no differences in ventilatory efficiency. Trends for improvements in 6MWT and 1STS in the exercise group were observed, but no differences were observed in strength or body composition. Among measures of QoL, general health determined by the SF-36 improved in the exercise group, but there were no differences between groups in cognitive function. CONCLUSIONS: MHD patients improved exercise capacity and some indices of QoL following a 12-week home-based exercise program. Home-based exercise is feasible for patients undergoing MHD and may help to obviate accessibility barriers to regular exercise.

Association of physical function and performance with peak VO2 in elderly patients with end stage kidney disease.

BACKGROUND: Physical function is impaired in end stage renal disease (ESRD). Various instruments have been used to assess the functional capabilities and health status of patients with ESRD, but it is not known which has the best association with peak VO2. AIMS: To assess the association between functional measures in ESRD. METHODS: Thirty nine elderly ESRD patients were evaluated with commonly used functional, health status, and quality of life measures, including maximal cardiopulmonary exercise testing (CPET), 6-min walk (6MWT), sit-to-stand test (STS), Veterans Specific Activity Questionnaire (VSAQ), upper and lower body strength, pulmonary function tests, and body composition determined by dual X-ray absorptiometry. The association between performance on these functional tools, clinical variables, and exercise test responses was assessed, and a non-exercise test multivariate model was developed to predict peak VO2. RESULTS: Peak VO2 was modestly related to VSAQ score (r = 0.59, p < 0.01), indices of upper and lower body strength (r = 0.45, p < 0.01 for both), and FEV1 (r = 0.51, p < 0.01). Functional and quality of life questionnaires were generally poorly related to one another and to peak VO2. In a multivariate model, 6MWT performance, forced expiratory volume in 1 s (FEV1), and VSAQ score were the best predictors of peak VO2, yielding a multiple R = 0.82, accounting for 67% of the variance in peak VO2. CONCLUSION: Exercise capacity can be reasonably estimated using non-exercise test variables in patients with ESRD, including a symptom questionnaire (VSAQ), 6MWT and FEV1. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov identifier: NCT01990495. Registered Nov 21, 2013.

Diffusion tensor tractography of brainstem fibers and its application in pain.

Evaluation of brainstem pathways with diffusion tensor imaging (DTI) and tractography may provide insights into pathophysiologies associated with dysfunction of key brainstem circuits. However, identification of these tracts has been elusive, with relatively few in vivo human studies to date. In this paper we proposed an automated approach for reconstructing nine brainstem fiber trajectories of pathways that might be involved in pain modulation. We first performed native-space manual tractography of these fiber tracts in a small normative cohort of participants and confirmed the anatomical precision of the results using existing anatomical literature. Second, region-of-interest pairs were manually defined at each extracted fiber's termini and nonlinearly warped to a standard anatomical brain template to create an atlas of the region-of-interest pairs. The resulting atlas was then transformed non-linearly into the native space of 17 veteran patients' brains for automated brainstem tractography. Lastly, we assessed the relationships between the integrity levels of the obtained fiber bundles and pain severity levels. Fractional anisotropy (FA) measures derived using automated tractography reflected the respective tracts' FA levels obtained via manual tractography. A significant inverse relationship between FA and pain levels was detected within the automatically derived dorsal and medial longitudinal fasciculi of the brainstem. This study demonstrates the feasibility of DTI in exploring brainstem circuitries involved in pain processing. In this context, the described automated approach is a viable alternative to the time-consuming manual tractography. The physiological and functional relevance of the measures derived from automated tractography is evidenced by their relationships with individual pain severities.

Brainstem atrophy in Gulf War Illness.

BACKGROUND: Gulf War Illness (GWI) is a condition that affects about 30 % of veterans who served in the 1990-91 Persian Gulf War. Given its broad symptomatic manifestation, including chronic pain, fatigue, neurological, gastrointestinal, respiratory, and skin problems, it is of interest to examine whether GWI is associated with changes in the brain. Existing neuroimaging studies, however, have been limited by small sample sizes, inconsistent GWI diagnosis criteria, and potential comorbidity confounds. OBJECTIVES: Using a large cohort of US veterans with GWI, we assessed regional brain volumes for their associations with GWI, and quantified the relationships between any regional volumetric changes and GWI symptoms. METHODS: Structural magnetic resonance imaging (MRI) scans from 111 veterans with GWI (Age = 49 ±â€¯6, 88 % Male) and 59 healthy controls (age = 51 ±â€¯9, 78 % male) were collected at the California War Related Illness and Injury Study Center (WRIISC-CA) and from a multicenter study of the Parkinson's Progression Marker Initiative (PPMI), respectively. Individual MRI volumes were segmented and parcellated using FreeSurfer. Regional volumes of 19 subcortical, 68 cortical, and 3 brainstem structures were evaluated in the GWI cohort relative to healthy controls. The relationships between regional volumes and GWI symptoms were also assessed. RESULTS: We found significant subcortical atrophy, but no cortical differences, in the GWI group relative to controls, with the largest effect detected in the brainstem, followed by the ventral diencephalon and the thalamus. In a subsample of 58 veterans with GWI who completed the Chronic Fatigue Scale (CFS) inventory of Centers for Disease Control and Prevention (CDC), smaller brainstem volumes were significantly correlated with increased severities of fatigue and depressive symptoms. CONCLUSION: The findings suggest that brainstem volume may be selectively affected by GWI, and that the resulting atrophy could in turn mediate or moderate GWI-related symptoms such as fatigue and depression. Consequently, the brain stem should be carefully considered in future research focusing on GWI pathology.

Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study.

BACKGROUND: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR). PURPOSE: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown. STUDY TYPE: Prospective longitudinal. SUBJECTS: Fifty-three subjects undergoing carotid endarterectomy or stenting. FIELD STRENGTH/SEQUENCE: 3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR). ASSESSMENT: We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery. STATISTICAL TESTS: PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P < 0.05, while the voxel-level significance threshold was set for P < 0.001. RESULTS: The entire group showed significant (cluster-level P < 0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P > 0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P < 0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P > 0.001) and cholesterol greater CBF decrease (P > 0.001). DATA CONCLUSION: The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734-747.

White Matter Asymmetry: A Reflection of Pathology in Traumatic Brain Injury.

Comparisons of white matter (WM) fractional anisotropy (FA) values between mild traumatic brain injury (mTBI) patients and controls have revealed inconsistencies in the directions of the resulting FA changes. To address these discrepancies, we examined hemispheric FA symmetry levels across WM tracts in 150 mTBI patients relative to 96 military controls. Automated fiber quantification was used to extract 18 WM tracts with 100 FA values, which were used to compute correlation strengths between the nine bilateral tract pairs. The Fisher z-transformed Pearson's r values were entered into an analysis of covariance examining the effects of group (mTBI and controls) and age on symmetry levels within each tract pair. The mTBI group displayed lower symmetry levels in the corticospinal tract and the inferior longitudinal fasciculus. Interactions between age and group were detected in the inferior fronto-occipital (IFOF), uncinate (UF), and superior longitudinal fasciculi (SLF). A similar pattern emerged in the IFOF and the UF, revealing age-related symmetry decreases in the mTBI patients despite stable levels of symmetry across ages in controls. In contrast, although the control group's symmetry levels actually increased with age in the SLF, no age-related symmetry changes were detected across the mTBI participants. Here, we proposed WM symmetry measures as a potential means of circumventing directional inconsistencies of trauma-related FA changes, as well as capturing more within-tract and within-subject variances of diffusion tensor imaging (DTI) metrics. Further, we demonstrated the method's utility in detecting mTBI-specific effects and their associated interactions with age.

A randomized controlled trial of exercise to prevent muscle mass and functional loss in elderly hemodialysis patients: Rationale, study design, and baseline sample.

BACKGROUND: Elderly maintenance hemodialysis (MHD) patients exhibit muscle wasting and impaired physical function. This trial determines whether MHD patients benefit from a 12-week home-based exercise program, protein supplementation, or both. DESIGN: and Methods: This is a randomized, blinded controlled trial involving 60 elderly MHD patients with impaired exercise capacity and function. Patients are randomized into either a homebased exercise program or normal care over a 12-week period. Measures at baseline include peak VO2, strength and body composition as well as cognitive and disease-specific questionnaires. Muscle biopsies are obtained and analyzed for protein signaling, expression of IGF-1, androgen receptors, and myostatin. RESULTS: At baseline, patient characteristics in the exercise and normal care groups were similar by age, gender and anthropomorphic measures. Peak VO2 was impaired (14.7 ±â€¯3.3 ml/kg/min), representing 55 ±â€¯14% of the age-predicted value. Six-minute walk distance was 322 ±â€¯71 m, and the mean 1-min sit to stand test was 18 ±â€¯8 repetitions, representing 69 ±â€¯16% and 55 ±â€¯22% of the age-predicted values, respectively. Indices of muscle function, including upper and lower body and hand grip strength all indicate marked impairment. Quality of life (QoL) using the SF36, the Beeson cognitive test, and KDQOL all suggest marked impairments compared to age-expected reference values for non-MHD patients. CONCLUSIONS: Patients undergoing MHD exhibit markedly reduced physical function and QoL. Thus, there are potentially significant gains to be made through a program of aerobic and resistance exercise. We anticipate this trial will demonstrate that home-based exercise improves cardiopulmonary function, protein signaling and QoL, and increases muscle mass, strength, and body composition.

Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions.

While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185-2194, 2016. © 2016 Wiley Periodicals, Inc.

Improved cardiovascular flow quantification with time-resolved volumetric phase-contrast MRI.

BACKGROUND: Cardiovascular flow is commonly assessed with two-dimensional, phase-contrast MRI (2-D PC-MRI). However, scan prescription and acquisition over multiple planes is lengthy, often requires direct physician oversight and has inconsistent results. Time-resolved volumetric PC-MRI (4-D flow) may address these limitations. OBJECTIVE: We assess the degree of agreement and internal consistency between 2-D and 4-D flow quantification in our clinical population. MATERIALS AND METHODS: Software enabling flow calculation from 4-D flow was developed in Java. With IRB approval and HIPAA compliance, 18 consecutive patients without shunts were identified who underwent both (1) conventional 2-D PC-MRI of the aorta and main pulmonary artery and (2) 4-D flow imaging. Aortic and pulmonary flow rates were assessed with both techniques. RESULTS: Both methods showed general agreement in flow rates (ρ: 0.87-0.90). Systemic and pulmonary arterial flow rates were well-correlated (ρ: 4-D 0.98-0.99, 2-D 0.93), but more closely matched with 4-D (P < 0.05, Brown-Forsythe). Pulmonary flow rates were lower than systemic rates for 2-D (P < 0.05, two-sample t-test). In a sub-analysis of patients without pulmonary or aortic regurgitation, 2-D showed improved correlation of flow rates while 4-D phase-contrast remained tightly correlated (ρ: 4-D 0.99-1.00, 2-D 0.99). CONCLUSION: 4-D PC-MRI demonstrates greater consistency than conventional 2-D PC-MRI for flow quantification.