The advanced activities of daily living: a tool allowing the evaluation of subtle functional decline in mild cognitive impairment

Objectives: Assessment of advanced activities of daily living (a-ADL) can be of interest in establishing the diagnosis of Alzheimer's disease (AD) in an earlier stage, since these activities demand high cognitive functioning and are more responsive to subtle changes. In this study we tested a new a-ADL tool, developed according to the International Classification of Functioning, Disability and Health (ICF). The a-ADL tool is based on the total number of activities performed (TNA) by a person and takes each subject as his own reference. It distinguishes a total Disability Index (a-ADL-DI), a Cognitive Disability Index (a-ADL-CDI), and a Physical Disability Index (a-ADL-PDI), with lower score representing more independency. We explored whether these indices allow distinction between cognitively healthy persons, patients with Mild Cognitive Impairment (MCI) and patients with mild AD. Methods: Participants were on average 80 years old (SD 4.6; 66-90), were community dwelling, and were diagnosed as (1) cognitively healthy subjects (n=26); (2) patients with MCI (n = 17), or (3) mild AD (n = 25), based upon extensive clinical evaluation and a set of global, cognitive, mood and functional assessments. The a-ADL-tool was not part of the clinical evaluation. Results: The a-ADL-CDI was significantly different between the three groups (p<.01). The a-ADL-DI was significantly different between MCI and AD (p<.001). The tool had good psychometrical properties (inter-rater reliability; agreement between patient and proxy; correlations with cognitive tests). Although the sample size was relatively small, ROC curves were computed for the a-ADL-DI and a-ADL-CDI with satisfactory and promising results. Conclusion: The a-ADL-CDI and a-ADL-DI might offer a useful contribution to the identification and follow up of patients with mild cognitive disorders in an older population

Reproducibility, accuracy and concordance of Accutrend® Plus for measuring circulating lipid concentration in adults

Introduction: The determination of lipid biomarkers by capillary sampling may be useful in the scree-ning, diagnosis and/or personal management of hyperlipidemia and cardiovascular risk. It remains unclear whether the use of the Accutrend® Plus system is appropriate. This study aimed to assess its reproducibility, accuracy and concordance for blood lipid profiling in adults. Materials and methods: Fasting capillary total cholesterol (TC) and triglyceride (TG) concentration on Accutrend® Plus were compared with their venous analogues obtained by a laboratory reference method in sixty-one adults (27 men and 34 women, aged 33.0 years). Supplementary capillary sam-pling was performed at two consecutive days taking into account macro-nutrient intake. Results: The day-to-day reproducibility of the Accutrend® Plus system proved to be high for TC (ICC = 0.85, P < 0.001), but moderate for TG (ICC = 0.68, P < 0.001). Strong correlations (r ≥ 0.80, P < 0.001) with the reference method were found for TC and TG. Mean difference (limits of agreement) were: 0.26 mmol/L (-0.95, 1.47) for TC, and -0.16 mmol/L (-1.29, 0.98) for TG. The concordance for subject classification according to the National Cholesterol Education Program (NCEP) guidelines was significant (P < 0.001), with substantial agreement for TC (κw = 0.67), and moderate agreement for TG (κw = 0.50). Conclusions: Day-to-day reproducibility of the Accutrend® Plus device for TC and TG is not optimal and lacks accuracy when compared to the reference laboratory method. The concordance between both methods for classifying subjects according to the NCEP is inadequate. Accutrend® Plus device should not be interchangeably used as a substitution for the standard laboratory methods in the diag-nosis of hyperlipidemia

Circulating Heat Shock Protein 70 in Health, Aging and Disease

<p>Abstract</p> <p>Background</p> <p>Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters.</p> <p>Results</p> <p>Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients.</p> <p>Conclusions</p> <p>The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.</p

Effects on muscle performance of NSAID treatment with Piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. a double blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp.</p> <p>Methods</p> <p>Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation.</p> <p>Results</p> <p>EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group.</p> <p>Conclusions</p> <p>Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN96340690">ISRCTN96340690</a></p

Exercise therapy for knee osteoarthritis pain:how does it work? A study protocol for a randomised controlled trial

INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATION NUMBER: NCT04362618.</p

Exercise therapy for knee osteoarthritis pain:how does it work? A study protocol for a randomised controlled trial

INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATION NUMBER: NCT04362618.</p

The feasibility of whole body vibration in institutionalised elderly persons and its influence on muscle performance, balance and mobility: a randomised controlled trial [ISRCTN62535013]

BACKGROUND: Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance. METHODS: Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 ± 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension. RESULTS: At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed. CONCLUSION: In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further