Sixteen Weeks of Aerobic Exercise does not Alter Resting-state Connectivity of the Precuneus in Patients with Alzheimer's Disease.

INTRODUCTION: In healthy elderly persons and patients with mild cognitive impairment, physical exercise can increase functional brain connectivity in the default mode network (DMN) measured by restingstate functional magnetic resonance imaging (rs-fMRI). However, no studies have so far investigated the effect of physical exercise on functional resting-state connectivity in the DMN in patients with Alzheimer's disease (AD). OBJECTIVE: In a single-blinded randomized controlled trial, we assessed the effects of an aerobic exercise intervention of 16 weeks of physical exercise on DMN connectivity using rs-fMRI in patients with AD. METHODS: Forty-five patients were randomly assigned to either a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All the patients underwent whole-brain rs-fMRI at 3 T, at baseline, and after 16 weeks. Since the posterior cingulate cortex (PCC) and adjacent precuneus constitute a central hub of the DMN, this parietal region was defined as region-ofinterest and used as the seed region for functional connectivity analysis of the rs-fMRI data treating age and gender as covariates. RESULTS: Neither seed-based analysis, seeded in the PCC/precuneus region nor ICA-based analyses, focusing on components of the DMN network, showed any exercise-induced changes in functional resting-state connectivity from baseline to follow-up. CONCLUSION: 16 weeks of aerobic exercise does not modify functional connectivity of the PCC/precuneus region in patients with AD. A longer intervention may be needed to show the effect of exercise on brain connectivity.

Participant evaluation of a behavioral intervention targeting reduction of sedentary behavior in patients with rheumatoid arthritis: a mixed methods study.

Purpose: The "Joint Resources - Sedentary Behavior Study" (JR-SB) revealed significant behavioral and cardio-metabolic effects of reducing daily sedentary behavior replaced by light-intensity physical activity in patients with rheumatoid arthritis. This study explores the participant perception and experiences of the intervention and impact on the participants' health, family and physical activity behavior.Materials and Methods: A mixed-methods study design, including quantitative and qualitative data, was applied. Quantitative data were collected post-intervention using a questionnaire (n = 69) evaluating experiences of participation in the intervention. By maximum variation sampling, 18 participants were recruited to three focus group interviews with discussions of intervention elements. Data from the two sub-studies were collected and analyzed separately, although integrated at the interpretation and reporting level.Results: Based on four overarching themes, results indicated participant satisfaction with the individually tailored, behavioral approach and the focus on light-intensity physical activity rather than higher intensities. Study participation had an additional positive impact on the behaviors of family and social relations. Conversely, the family motivated the participants to achieve their physical activity goals.Conclusions: The study results support the use of individually tailored and behavioral approaches to reduce sedentary behavior, increase light-intensity physical activity and improve physical abilities in patients with rheumatoid arthritis. IMPLICATIONS FOR REHABILITATIONThis paper presents positive participant perception and motivation for an individually tailored, behavioural intervention that aimed to reduce sedentary behaviour replaced by light-intensity physical activity in patients with rheumatoid arthritis.The results indicate that especially the focus on light-intensity physical activity, a consistent focus on the individual's everyday life and continuous support from health professionals motivated the participants to reduce their daily sedentary behaviour - also in the long term.Involvement of participants' family members seems to have influence on their own physical activity behavior as well as on the participants' motivation for changing physical activity behavior.Together with earlier evidence, the results underpin the use of behavioural strategies to support patients with rheumatoid arthritis in achieving their physical activity goals and in improving the abilities needed to manage their everyday lives.

Exercise in patients with hip osteoarthritis - effects on muscle and functional performance: A randomized trial.

BACKGROUND: It is believed that clinical management of osteoarthritis should address muscle weakness to improve physical function and prevent disability and frailty. OBJECTIVES: This sub-study investigated the effects of supervised progressive resistance training (RT), supervised Nordic Walking (NW), and unsupervised home-based exercise (HBE) on muscle and functional performance; and associations between these exercise-induced changes in persons with hip osteoarthritis. METHODS: Forty-two patients with hip osteoarthritis were recruited from a larger RCT (NCT01387867). All the groups (RT, n = 15; NW, n = 12; HBE, n = 15) exercised 1 h 3 times/week for 4 months. Quadriceps cross-sectional area (QCSA, MRI-determined); quadriceps strength (QMVC); leg extensor power (LEP); functional performance (chair stands (30sCS); stair climbs (TSC); and 6-minute walk (6MWT)) were assessed at baseline and 4 months. RESULTS: Per protocol analyses (one-way ANOVA and Bonferroni test) showed significant between-group differences for improvements in QCSA in the most symptomatic leg favoring RT versus NW (2.3 cm2, 95% CI [0.6, 3.9]) and HBE (2.3 cm2 [0.8, 3.9]); and 30sCS (1.8 repetitions [0.2-3.3]), and 6MWT (35.1 m [3.5-66.7]) favoring NW versus HBE. Associations existed between exercise-induced changes in QCSA and QMVC (r = 0.366, p = .019) for the most symptomatic leg and between changes in 6MWT and QMVC (r = 0.320, p = .04) and LEP (r = 0.381, p = .01), respectively, for the least symptomatic leg. CONCLUSIONS: Resistance training appeared effective for improving muscle mass, but less effective for improving muscle strength, power, and functional performance. Only exercise-induced changes in muscle strength and power of the least symptomatic leg, not the most symptomatic leg, were related to changes in functional performance.

Inter-Day Test-Retest Reproducibility of the CAT, CCQ, HADS and EQ-5D-3L in Patients with Severe and Very Severe COPD.

INTRODUCTION: In patients with COPD, the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and EuroQol 5D (EQ-5D-3L) are widely used patient reported outcome measures (PROMs) of respiratory symptoms, anxiety, depression and quality of life. Despite established validity, responsiveness and minimal important change (MIC), the reproducibility and especially important agreement parameters remain unreported in these frequently used PROMs. The aim of this study was to investigate the inter-day test-retest reliability and agreement of the CAT, CCQ, HADS and EQ-5D-3L in patients with severe and very severe COPD (FEV1 <50%) eligible for hospital-based pulmonary rehabilitation. PATIENTS AND METHODS: Fifty patients (22 females, mean [SD] age 67 [9] yrs.; FEV1 32[9] %; 6-minute walk distance 347 [102] meters; CAT 21 [6] points; BMI: 26 [6] kg/m2) completed the questionnaires (CAT, CCQ, HADS, EQ-5D-3L) in combination with functional performance test instructed by one assessor on test-day one (T1) and by another assessor 7-10 days later on test-day two (T2). RESULTS: The inter-day test-retest reliability ICC was 0.88 (LL95CI: 0.80) for CAT; 0.69 (LL95CI: 0.46) for CCQ; 0.86 (LL95CI: 0.75) and 0.90 (LL95CI: 0.82) for HADS-anxiety (A) and depression (D) and 0.87 (LL95CI: 0.76) for EQ-5D-VAS. The corresponding agreements within a single measurement (standard error of measurement, SEM) and for repeated measurement errors (smallest real difference, SRD) were respectively 2.1 and 2.9 points for CAT; 0.5 and 0.7 points for CCQ total; 1.3 and 1.9 points for HADS-A; 0.9 and 1.3 points for HADS-D and 6.8 and 9.7 VAS-score for EQ-5D-3L, respectively. Ceiling/flooring effect was present in <5% for all questionnaires. CONCLUSION: In patients with severe and very severe COPD, the CAT, CCQ, HADS and EQ-5D-3L questionnaires presented moderate to excellent inter-day test-retest reliability, and no floor or ceiling effect was documented for any of the questionnaires. Only CAT and HADS had an acceptable SRD below the established MIC for assessing change over time on group level, and none of the PROMS were fit to assess individual changes over time.

The Impact of Self-Efficacy on Activity Limitations in Patients With Hip Osteoarthritis: Results From a Cross-Sectional Study.

OBJECTIVE: Pain and activity limitations are the main health complaints in osteoarthritis. We explored pathways between pain and activity limitations in a chain mediation model that involved self-efficacy, physical activity behavior, and muscle function in patients with hip osteoarthritis not awaiting hip replacement. METHODS: We used cross-sectional, baseline data from a randomized controlled trial on 152 patients with clinical hip osteoarthritis according to the American College of Rheumatology not awaiting hip replacement. The associations between pain, self-efficacy, self-reported physical activity, muscle function (leg extensor power), and activity limitations (performance-based and self-reported activity limitation outcomes) were modeled using structural equation models. RESULTS: The effect of pain on performance-based activity limitation was fully mediated by self-efficacy, physical activity, and muscle function. Of the total effect of self-efficacy on performance-based activity limitation, the direct effect accounted for 63% (95% CI: 45%-82%), whereas the indirect effect via physical activity constituted 16% (95% CI: 1%-30%) and the indirect effect via muscle function constituted 21% (95% CI: 9%-32%). In contrast, physical activity and muscle function had no effect on self-reported activity limitations, whereas pain had a direct effect and an indirect effect mediated by self-efficacy. CONCLUSION: Our results suggest that self-efficacy should be taken into consideration in prevention and treatment of activity limitations in patients with hip osteoarthritis not awaiting hip replacement. Coupling exercise with programs of self-efficacy enhancement could potentially increase the positive effects of exercise.

The role of physical and cognitive function in performance of activities of daily living in patients with mild-to-moderate Alzheimer's disease - a cross-sectional study.

BACKGROUND: Several factors may play a role in the ability of patients with Alzheimer's disease to perform activities of daily living (ADL). The aim of this study was to examine the impact of different aspects of physical performance and cognitive functions on ADL in patients suffering from mild-to-moderate Alzheimer's disease. METHODS: We conducted secondary analyses on cross-sectional baseline data from the randomized controlled multicentre study "Preserving quality of life, physical health and functional ability in Alzheimer's Disease: The effect of physical exercise" (ADEX). In total, 185 AD patients (76 women and 109 men), with a mean age on 70,4 years, were included. Data from physical performance tests (Astrand cycle test, Timed up & Go (TUG), Sit to Stand test (STS)) and cognitive tests (Mini Mental Status Examination (MMSE), Symbol Digit Modalities Test (SDMT), Stroop Color and Word test (Stroop)) were used. Their associations with ADL, measured on the ADCS-ADL scale was assessed in multivariable regression analyses. RESULTS: SDMT and MMSE had significant, moderate correlations with total ADL (SDMT: r = 0.33, MMSE: r = 0.42) and instrumental ADL (SDMT: r = 0.31, MMSE: r = 0.42), but not with basic ADL. Adjusting for age and sex, the associations between SDMT and MMSE to total ADL and instrumental ADL persisted. No significant associations were found between Astrand, TUG, STS or Stroop and total ADL, basic ADL or instrumental ADL. CONCLUSION: Total ADL and instrumental ADL are associated with cognitive functions, including executive function. No significant association between examined physical performance parameters and ADL functions was observed, and consequently does not support an impact of physical function on ADL functions in patients with mild-to-moderate Alzheimer's disease and relatively well-preserved physical function. Strategies aimed to improve cognition may be better suited to improve ADL function in patients with mild-to-moderate Alzheimer's disease. TRIAL REGISTRATION: NCT01681602 . Registered 10 September 2012, retrospectively registered.

Health-Related Quality of Life and Physical Function in Individuals with Parkinson's Disease after a Multidisciplinary Rehabilitation Regimen-A Prospective Cohort Feasibility Study.

Parkinson's disease (PD) is a neurodegenerative disease and a multidisciplinary approach to rehabilitation has been suggested as the best clinical practice. However, very few studies have investigated the long-term effects of a multidisciplinary rehabilitation approach, particularly regarding whether this can slow the progression of PD. The purpose was to investigate the short- and long-term effect of a 2-week multidisciplinary rehabilitation regimen on the PD-related decline in health-related quality of life (HRQOL), mobility, and muscle function. Individuals with PD (IPD) participated in a 2-week inpatient multidisciplinary rehabilitation regimen that focused on improving HRQOL, mobility, and muscle function. Data from the primary outcome: HRQOL (Parkinson's Disease Questionnaire 39, PDQ-39), secondary outcomes: handgrip strength, Timed-up and Go (TUG), Hospital Anxiety and Depression Scale (HADS), and Falls Efficacy Scale-International (FES-I) were compared at pre-visitation, before and after the 2-week regimen, and again at 4 and 10 months follow-up. In total, 224 patients with PD were included. There were short-term improvements in all outcomes. PDQ-39 was maintained at the same level as pre-visitation after 10 months follow-up. A 2-week multidisciplinary rehabilitation regimen improved short-term mobility, muscle function, and HRQOL in individuals with Parkinson's disease. HRQOL was maintained after 10 months demonstrating long-term effects.

12-months follow-up of pulmonary tele-rehabilitation versus standard pulmonary rehabilitation: A multicentre randomised clinical trial in patients with severe COPD.

Between March 2016 and October 2017, we randomised 134 patients with severe COPD from 8 hospitals in the Capital Region of Denmark to participate in either standardised, outpatient pulmonary rehabilitation (control group) or on-line, supervised and home-based tele-rehabilitation (intervention group). We found no difference between the groups in the primary outcome: six minutes walking distance (6MWD) after completion of the programme. The current study presents results from the 12-month follow-up with assessment of the 6MWD and analyses of hospitalisation and mortality. There were no significant differences between or within the groups in the 6MWD one year after completion of the programme.

Physical Exercise May Increase Plasma Concentration of High-Density Lipoprotein-Cholesterol in Patients With Alzheimer's Disease.

Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n = 90) or treatment as usual (n = 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.

Supervised pulmonary tele-rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicentre trial.

RATIONALE: Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD. Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported. Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR). OBJECTIVE: To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR. METHODS: In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly). Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks' follow-up from baseline. The primary analysis was based on the intention-to-treat principle. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised. The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: -6.6 to 24.9)) or at 22 weeks' follow-up (-5.3 metres (95% CI: -28.9 to 18.3)). More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01). CONCLUSION: PTR was not superior to conventional PR on the 6MWD and we found no differences between groups. As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design. Trial registration number ClinicalTrials.gov (NCT02667171), 28 January 2016.

Sustained Long-Term Efficacy of Motivational Counseling and Text Message Reminders on Daily Sitting Time in Patients With Rheumatoid Arthritis: Long-Term Follow-up of a Randomized, Parallel-Group Trial.

OBJECTIVE: To evaluate the 18-month postintervention efficacy following a 4-month individually tailored behavioral intervention on daily sitting time in patients with rheumatoid arthritis (RA). METHODS: In an observer-blinded randomized trial, 150 RA patients were included. During 4 months, the intervention group (n = 75) received 3 motivational counseling sessions and tailored text messages aimed at increasing light-intensity physical activity through reduction of sedentary behavior. The control group (n = 75) maintained their usual lifestyle. The primary outcome was change from baseline to 18 months postintervention in objectively measured daily sitting time (using ActivPAL). Secondary outcomes included changes in clinical patient-reported outcomes and cardiometabolic biomarkers. A mixed-effect repeated measures analysis of covariance model in the intent-to-treat population was applied. RESULTS: At 22 months follow-up from baseline, 12 participants were lost to follow-up. Compared to baseline, sitting time in the intervention group decreased 1.10 hours/day, whereas it increased by 1.32 hours/day in the control group, a between-group difference of -2.43 hours/day (95% confidence interval [95% CI] -2.99, -1.86; P < 0.0001) favoring the intervention group. For most secondary outcomes, between-group differences favored the intervention: visual analog scale (VAS) pain -15.51 mm (95% CI -23.42, -7.60), VAS fatigue -12.30 mm (95% CI -20.71, -3.88), physical function -0.39 Health Assessment Questionnaire units (95% CI -0.53, -0.26), total cholesterol -0.86 mmoles/liter (95% CI -1.03, -0.68), triglycerides -0.26 mmoles/liter (95% CI -0.43, -0.09), and average glucose -1.15 mmoles/liter (95% CI -1.39, -0.91). CONCLUSION: The 4-month postintervention results showed that patients in the intervention reduced their daily sitting time and improved patient-reported outcomes and total cholesterol levels compared to the control group. Eighteen months after intervention, patients in the intervention group were still significantly less sedentary than controls. Findings suggest that a behavioral approach is beneficial for promoting long-term physical activity and health in patients with RA.

A randomized controlled trial of the effect of supervised progressive cross-continuum strength training and protein supplementation in older medical patients: the STAND-Cph trial.

BACKGROUND: During hospitalization, older adults (+ 65 years) are inactive, which puts them at risk of functional decline and loss of independence. Systematic strength training can prevent loss of functional performance and combining strength training with protein supplementation may enhance the response in muscle mass and strength. However, we lack knowledge about the effect of strength training commenced during hospitalization and continued after discharge in older medical patients. This assessor-blinded, randomized study investigated the effect of a simple, supervised strength training program for the lower extremities, combined with post-training protein supplementation during hospitalization and in the home setting for 4 weeks after discharge, on the effect on change in mobility in older medical patients. METHODS: Older medical patients (≥ 65 years) admitted acutely from their home to the Emergency Department were randomized to either standard care or supervised progressive strength training and an oral protein supplement during hospitalization and at home 3 days/week for 4 weeks after discharge. The primary outcome was between-group difference in change in mobility from baseline to 4 weeks after discharge assessed by the De Morton Mobility Index, which assesses bed mobility, chair mobility, static and dynamic balance, and walking. Secondary outcomes were 24-h mobility, lower extremity strength, gait speed, grip strength and activities of daily living. RESULTS: Eighty-five patients were randomized to an intervention group (N = 43) or a control group (N = 42). In the intervention group, 43% were highly compliant with the intervention. Our intention-to-treat analysis revealed no between-group difference in mobility (mean difference in change from baseline to 4 weeks, - 4.17 (95% CI - 11.09; 2.74; p = 0.24) nor in any of the secondary outcomes. The per-protocol analysis showed that the daily number of steps taken increased significantly more in the intervention group compared to the control group (mean difference in change from baseline to 4 weeks, 1033.4 steps (95% CI 4.1; 2062.7), p = 0.049, adjusted for mobility at baseline and length of stay; 1032.8 steps (95% CI 3.6; 2061.9), p = 0.049, adjusted for mobility at baseline, length of stay, and steps at baseline). CONCLUSIONS: Simple supervised strength training for the lower extremities, combined with protein supplementation initiated during hospitalization and continued at home for 4 weeks after discharge was not superior to usual care in the effect on change in mobility at 4 weeks in older medical patients. For the secondary outcome, daily number of steps, high compliance with the intervention resulted in a greater daily number of steps. Less than half of the patients were compliant with the intervention indicating that a simpler intervention might be needed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01964482. Registered on 14 October 2013. Trial protocol PubMed ID (PMID), 27039381.

Influence of between-limb asymmetry in muscle mass, strength, and power on functional capacity in healthy older adults.

PURPOSE: Numerous daily tasks such as walking and rising from a chair involve bilateral lower limb movements. During such tasks, lower extremity function (LEF) may be compromised among older adults. LEF may be further impaired due to high degrees of between-limb asymmetry. The present study investigated the prevalence of between-limb asymmetry in muscle mass, strength, and power in a cohort of healthy older adults and examined the influence of between-limb asymmetry on LEF. METHODS: Two hundred and eight healthy older adults (mean age 70.2 ± 3.9 years) were tested for LEF (400 m walking and 30-seconds chair stand). Furthermore, maximal isometric and dynamic knee extensor strength, leg extensor power, and lower limb lean tissue mass (LTM) were obtained unilaterally. RESULTS: Mean between-limb asymmetry in maximal muscle strength and power ranged between 10% and 13%, whereas LTM asymmetry was 3 ± 2.3%. Asymmetry in dynamic knee extensor strength was larger for women compared with men (15.0 ± 11.8% vs 11.1 ± 9.5%; P = .005) Leg strength and power were positively correlated with LEF (r2  = .43-.46, P < .001). The weakest leg was not a stronger predictor of LEF than the strongest leg. Between-limb asymmetry in LTM and isometric strength was negatively associated with LEF (LTM; r2  = .12, P = .005, isometric peak torque; r2  = 0.40, P = .03.) but dynamic strength and power were not. CONCLUSION: The present study supports the notion that in order to improve or maintain LEF, healthy older adults should participate in training interventions that increase muscle strength and power, whereas the effects of reducing between-limb asymmetry in these parameters might be of less importance.

Moderate- to high-intensity exercise does not modify cortical ß-amyloid in Alzheimer's disease.

INTRODUCTION: Animal models of Alzheimer's disease show that exercise may modify ß-amyloid (Aß) deposition. We examined the effect of a 16-week exercise intervention on cortical Aß in patients with mild-to-moderate Alzheimer's disease. METHODS: Thirty-six patients with Alzheimer's disease were randomized to either one hour of aerobic exercise three times weekly for 16 weeks or usual care. Pre and post intervention, 11Carbon-Pittsburgh compound B positron emission tomography was carried out to assess cortical Aß, and quantified using standardized uptake value rations (SUVRs). RESULTS: The intervention showed no effect on follow-up SUVRs in a covariance analysis with group allocation, baseline intervention SUVR, age, sex, and baseline Mini-Mental State Examination as predictors. Change in SUVRs did not correlate with changes in measures of physical or aerobic fitness. DISCUSSION: The present findings do not support an effect of exercise on Aß. However, the relatively short intervention period may account for a lack of efficacy. Further studies should test earlier and longer interventions.

Patients with Alzheimer's disease who carry the APOE ε4 allele benefit more from physical exercise.

INTRODUCTION: Our group has completed an exercise study of 200 patients with mild Alzheimer's disease. We found improvements in cognitive, neuropsychiatric, and physical measures in the participants who adhered to the protocol. Epidemiological studies in healthy elderly suggest that exercise preserves cognitive and physical abilities to a higher extent in AP OE ε4 carriers. METHODS: In this post hoc subgroup analysis study, we investigated whether the beneficial effect of an exercise intervention in patients with mild AD was dependent on the patients' APOE genotype. RESULTS: We found that patients who were APOE ε4 carriers benefitted more from the exercise intervention by preservation of cognitive performance and improvement in physical measures. DISCUSSION: This exploratory study establishes a possible connection between the beneficial effects of exercise in AD and the patients' APOE genotype. These findings, if validated, could greatly impact the clinical management of patients with AD and those at risk for developing AD.

Assessment of Mobility in Older People Hospitalized for Medical Illness Using the de Morton Mobility Index and Cumulated Ambulation Score-Validity and Minimal Clinical Important Difference.

BACKGROUND AND PURPOSE: Older adults acutely hospitalized for medical illness typically have comorbidity and disability, and in-hospital physical inactivity greatly increases the likelihood of developing new disability. Thus, assessment of the patients' mobility status is crucial for planning and carrying out targeted interventions that ensure mobilization during hospital admission. The aim of this study was to determine convergent validity, known group validity, floor and ceiling effects, and anchor-based minimal clinically important difference (MCID) of the more time-consuming de Morton Mobility Index (DEMMI) and the less time-consuming Cumulated Ambulation Score (CAS) in older adults acutely hospitalized for medical illness. METHODS: In this multicenter cohort study, 235 older hospitalized adults, with a mean (standard deviation) age of 84.8 (7.1) years, were consecutively included. Assessments of mobility using the DEMMI (score range 0-100), the CAS (score range 0-6), and the Barthel Index (BI, score range 0-100) were performed by physical or occupational therapists at hospital admission and discharge. In addition, at discharge patients and therapists were independently asked to assess the patients' current mobility status compared with their mobility status at hospital admission using the Global Rating of Change scale. RESULTS AND DISCUSSION: Complete data sets were obtained for 155 patients. Baseline characteristics of those with complete data sets did not differ from those with incomplete data sets, except for the number of secondary diagnoses, which was lower in the latter. Significant and moderate relationships existed both at admission and at discharge between scores in the DEMMI and the BI (rs = 0.68, P < .0001, and rs = 0.71, P < .0001), and between scores in the CAS and the BI (rs = 0.60, P < .0001, and rs = 0.57, P < .0001). Use of a gait aid and discharge to inpatient rehabilitation or nursing home were associated with significantly lower DEMMI and CAS scores. No floor or ceiling effects were present in the DEMMI, while a ceiling effect was present in the CAS. The MCID scores based on patients' assessments were 10.7 points for the DEMMI and 0.67 for the CAS. CONCLUSIONS: These data show that the DEMMI is valid and responsive to changes in mobility and can be considered to have the required properties for measuring mobility in older adults who are hospitalized in medical and geriatric wards. In contrast, the CAS appears to be appropriate to identify whether a patient is independently mobile or needs assistance, while the measure is less suitable for measuring improvements in mobility.

Intra- and inter-rater reproducibility of the 6-minute walk test and the 30-second sit-to-stand test in patients with severe and very severe COPD.

BACKGROUND: In patients with COPD, the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30sec-STS) are widely used as clinical outcome measures of walking capacity, lower limb muscle strength, and functional ability. Due to a documented learning effect, at least two trials are recommended for assessment. The aim of our study was to investigate the intra- and inter-rater reliability and agreement of the two tests in patients with severe and very severe COPD (FEV1 <50%). PATIENTS AND METHODS: Fifty patients (22 females; mean [SD]: age 67 [9] years, FEV1 predicted 32 [9]%) were assessed with the 6MWT and the 30sec-STS twice by the same assessor on test-day 1 (T1) and by another assessor 7-10 days later on test-day 2 (T2). RESULTS: The 6MWT intra- and inter-rater reliability (intraclass correlation coefficient, ICC1.1) was 0.98 (lower limit 95% CI: 0.94) and 0.96 (lower limit 95% CI: 0.94), respectively, and agreement (standard error of the measurement, SEM) was 14.8 and 20.5 m, respectively. The 30sec-STS intra- and inter-rater reliability and agreement results were, respectively, ICC1.1 0.94 (lower limit 95% CI: 0.90) and 0.92 (lower limit 95% CI: 0.86), with SEM of 0.97 and 1.14 repetitions. There was no difference (95% CI: -5.3; 8.1) between the 6MWT distances on T1, while the mean walking distance improved 7.9 m (0.0 m; 15.8 m) from T1 to T2. Improvement on the same test date was less likely (OR: 3.6 [95% CI: 1.1; 11.8], Fisher's exact test, P=0.047) in patients who walked less than 350 m in the 6MWT. We found no clinically relevant learning effect in the 30sec-STS. CONCLUSION: In patients with severe and very severe COPD the 6MWT and the 30sec-STS showed excellent intra- and inter-rater reliability and acceptable agreement. No learning effect was documented for the tests when performed on the same day. Our data suggest that in clinical practice using different assessors is acceptable, and that a single test trial may be sufficient to assess patients with severe and very severe COPD.

Change in Fitness and the Relation to Change in Cognition and Neuropsychiatric Symptoms After Aerobic Exercise in Patients with Mild Alzheimer's Disease.

BACKGROUND: Physical activity has the potential to improve physical function in patients with Alzheimer's disease (AD) and may contribute to modify disease processes and cognitive function. OBJECTIVE: The aim of this study was to investigate 1) the effect of moderate-high-intensity aerobic exercise on cardiorespiratory fitness, i.e., peak oxygen uptake (VO2peak) determined by direct breath-by-breath cardiopulmonary exercise test, and 2) the association between changes in VO2peak and changes in cognition and neuropsychiatric symptoms in patients with mild AD. METHODS: The study is based on secondary outcome analyses from the large single-blinded multi-center study ADEX (Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise). A preselected sub-group of 55 participants (age 52-83 years), 29 from the intervention group (IG) and 26 from the control group (CG), was included. IG performed 16 weeks of supervised moderate-to-high intensity aerobic exercise. Assessments of VO2peak, mental speed and attention (Symbol Digit Modalities Test, SDMT), and neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI) were performed at baseline and at 16 weeks. RESULT: VO2peak increased 13% in the IG and a between-group difference in mean change (3.92 ml/kg/min, 95% CI 6.34-1.51, p = 0.003) was present in favor of the IG. Combined data from IG and CG showed positive associations between changes in VO2peak and changes in NPI (Rho = - 0.41, p = 0.042) and changes in SDMT (Rho = 0.36, p = 0.010), respectively. CONCLUSION: Aerobic exercise improves VO2peak in community-dwelling patients with mild AD. Furthermore, changes in VO2peak appear to be associated to changes in cognition and neuropsychiatric symptoms.

Exercise induced effects on muscle function and range of motion in patients with hip osteoarthritis.

BACKGROUND AND PURPOSE: Patients with hip osteoarthritis have impairments in muscle function (muscle strength and power) and hip range of motion (ROM), and it is commonly believed that effective clinical management of osteoarthritis should address these impairments to reduce pain and disability. Therefore, the purpose of this study was to compare the short- and long-term effects of 4 months of physiotherapist-supervised strength training, physiotherapist-supervised Nordic Walking (NW), or unsupervised home-based exercise (HBE) on muscle function and hip ROM in patients diagnosed with hip osteoarthritis. METHODS: Secondary outcome analyses from an observer-blinded three-armed parallel-design randomized controlled trial in 60+-year-old patients with clinical hip osteoarthritis (American College of Rheumatology criteria) who were not on a waiting list for hip replacement. One hundred and fifty-two patients were randomized to either 4 months of physiotherapist-supervised, moderate, progressive, strength training (n = 50), physiotherapist-supervised NW (n = 50), or unsupervised HBE (n = 52). Maximal isometric hip and thigh muscle strength and leg extensor power and active hip ROM were assessed at baseline 2, 4, and 12 months. RESULTS: Intention-to-treat-analyses did not show any significant between-group differences for improvements in muscle strength and power or ROM at any time points. Short-term significant (p < .05) increases in muscle strength were present in the physiotherapist-supervised exercise groups and in the long-term for muscle power in the NW-group. All exercise modes resulted in significant increases of ROM but long-term improvements were only shown for NW and HBE. DISCUSSION: Four months of physiotherapist-supervised, progressive, moderate, and strength training was less effective than hypothesized for improving muscle strength and power in patients with hip osteoarthritis who are not awaiting hip replacement. Our results may indicate that in these patients, improvements in disability are not necessarily dependent on improvements in strength and power or ROM.

Exploring PTDH-P450BM3 Variants for the Synthesis of Drug Metabolites.

The conversion of a series of pharmaceutical compounds was examined with three variants of cytochrome P450BM3 fused to phosphite dehydrogenase (PTDH) to enable cofactor recycling. Conditions for enzyme production were optimized, and the purified PTDH-P450BM3 variants were tested against 32 commercial drugs by using rapid UPLC-MS analysis. The sets of mutations (R47L/F87V/L188Q and R47L/F87V/L188Q/E267V/G415S) improved conversion for all compounds, and a variety of products were detected. Product analysis showed that reaction types included C-hydroxylation, N-oxidation, demethylation, and aromatization. Interestingly, enzymatic aromatization could occur independent of the addition of reducing coenzyme. These results identified new conversions catalyzed by P450BM3 variants and showed that a small set of mutations in the oxygenase domain could broaden both substrate range and reaction type.