Comparison between Two Different Handgrip Systems and Protocols on Force Reduction in Handgrip Assessment.

INTRODUCTION: Fatigue resistance (FR) can be assessed as the time during which grip strength (GS) drops to 50% of its maximum during a sustained maximal voluntary contraction. For the first time, we compared force-time characteristics during FR test between two different handgrip systems and investigated age- and clinical-related differences in order to verify if a briefer test protocol (i.e., until 75%) could be sufficiently informative. METHODS: A cohort of young healthy controls (Y, <30 y, 24 ± 3 y, 54% women), middle-aged (MA, 30-65 y, 47 ± 11 y, 54% women), and older (OLD, >65 y, 77 ± 7 y, 50% women) community-dwelling persons, and hospitalized geriatric patients (HOSP, 84 ± 5 y, 50% women) performed the FR test. For this purpose, an adapted vigorimeter (original rubber bulb of the Martin Vigorimeter connected to a Unik 5000 pressure gauge) here defined as "pneumatic handgrip system" (Pneu) and Dynamometer G200 system (original Jamar Dynamometer handle with an in-build strength gauge) here defined as "hydraulic handgrip system" (Hydr) were used. Force-time curves were analysed from 100% to 75% and from 75% to 50% of the initial maximal GS during the FR test. The area under the curve (GW) was calculated by integrating the actual GS at each time interval (i.e., 1/5,000 s) and corrected for body weight (GW/body weight). RESULTS: For both systems, we found fair associations between FR100-50 and FR100-75 (Pneu mean difference = 50.1 s [95% CI: 47.9-52.4], r2 = 0.48; Hydr mean difference = 28.4 s [95% CI: 27.0-29.7], r2 = 0.52, all p < 0.001) and also moderate associations between GW(100-50)/body weight and GW(100-75)/body weight (Pneu mean difference = 32.1 kPa*s/kg [95% CI: 30.6-33.6], r2 = 0.72; Hydr mean difference = 8.1 kg*s/kg [95% CI: 7.7-8.6], r2 = 0.68, all p < 0.001). Between MA and OLD, we found a significant age-related difference in the GW results in the first 25% strength decay for Pneu (10.2 ± 0.6 kPa*s/kg against 7.1 ± 1.2 kPa*s/kg, respectively). CONCLUSION: The brief test protocol is valid. Differences within the first 25% strength decay in GW between OLD and HOSP were identified when using Pneu but not when using Hydr. Therefore, a brief FR test protocol using a continuous registration of the strength decay seems to be sufficiently informative in a clinical setting to appraise muscle fatigability, however, only when using a Pneu system.

Hearing aid use and gender differences in the auditory-cognitive cascade in the oldest old.

OBJECTIVES: This study analyzed cognitive differences between hearing-aid (HA) and non-HA users. We hypothesized that HA-use attenuates the auditory-cognitive cascade, thereby, the latter is more conspicuous in non-HA users. Since hearing impairment (HI) shows male predominance, we hypothesized gender differences within the auditory-cognitive relationship. METHODS: Non-frail community-dwellers ≥ 80 years were assessed for HI (pure tone audiogram-PTA; speech reception threshold-SRT) and global and domain-specific cognitive impairments (Mini-Mental State Examination-MMSE; Montreal Cognitive Assessment-MOCA; Reaction Time Test-RT1-4). Pearson and partial correlations (correcting for age and PTA) assessed auditory-cognitive associations within gender and HA subgroups. Fisher's z test compared correlations between HA and non-HA users. RESULTS: 126 participants (age range 80-91 years) were included. HA-use prevalence was 21%. HA-users were older with worse HI (mean PTA 49.5dBHL). HA-users exhibited no significant auditory (PTA, SRT) and cognitive (MMSE, MOCA, RT1- RT4) correlations. Male non-HA users, displayed a significant association between HI and global cognition, processing speed, selective and alternating attention. Significant differences were noted between MMSE and PTA and SRT (z-score 2.28, 3.33, p = 0.02, <0.01, respectively) between HA and non-HA users. CONCLUSION: Male non-HA users displayed an association between HI and global and domain-specific (processing speed; selective and alternating attention) cognitive decline. Associations between global cognition and HI were significantly different between HA and non-HA users. This may be partially attributable to underlying subgroups sample sizes and statistical power disparity. If larger scale longitudinal or interventional studies confirm these findings, timely HI assessment and management may be the cornerstone for delaying cognitive decline.

Leptomeningeal metastasis in a marginal zone lymphoma, presenting as a delirium: case report.

BACKGROUND: Hematologic malignancies can spread to the central nervous system (CNS), either as focal lesions or as leptomeningeal disease. Marginal zone lymphoma (MZL) is a low-grade non-Hodgkin lymphoma and generally presents as an indolent disease. This case report illustrates an unexpected diagnosis of leptomeningeal metastasis in an MZL, presenting as a delirium without B symptoms, pronounced hematologic progression or abnormalities on cerebral imaging. CASE PRESENTATION: An 80-year-old patient with a medical history of monoclonal B-cell lymphocytosis (MBL) with a clone indicative for an MZL, presented to the emergency and the geriatric departments with a recent cognitive deterioration and behavioral changes. MMSE score was 18/30. After excluding the most common etiologies through classical work-up including a normal head magnetic resonance imaging, a lumbar puncture was performed. In the cerebrospinal fluid an elevated protein level and increased lymphocyte count were identified, whereas beta-amyloid and tau protein levels were normal. Immunophenotyping of the lymphocytes confirmed CNS invasion by the MZL clone. Staging revealed mild splenomegaly. Prednisolone, intrathecal and systemic chemotherapy were initiated, leading to quick cognitive improvement with a final MMSE score of 28/30. CONCLUSIONS: To the best of our knowledge a delirium in an older patient due to leptomeningeal disease in MZL has never been described. To date, rare reports of CNS invasion by MZL describe focal intracranial lesions. After exclusion of common etiologies, physicians should remain vigilant when confronted with a patient with history of MBL presenting neurological symptoms. This case illustrates the importance of low threshold for lumbar punctures in this population, also for those patients with normal imaging studies.

Six weeks of strength endurance training decreases circulating senescence-prone T-lymphocytes in cytomegalovirus seropositive but not seronegative older women.

BACKGROUND: Ageing is associated with a decline in immune function termed immunosenescence. This process is characterized amongst others by less naive T-cells and more senescent phenotypes, which have been implicated in the pathogenesis of many age-related diseases. Thus far, reports regarding the long-term adaptation effects of exercise on T-cell phenotypes are scant and largely equivocal. These inconsistencies may be due to potential contributors to immunosenescence, particularly cytomegalovirus infection, which is considered a hallmark of T-cell senescence. Therefore, we sought to investigate the impact of cytomegalovirus serostatus on the distribution of peripheral T-cell subsets following long-term exercise in older women. METHODS: One hundred women (aged 65 years and above) were randomized to 3 times/weekly training at either intensive strength training (3 × 10 repetitions at 80% of one-repetition maximum, n = 31), strength endurance training (2 × 30 repetitions at 40% of one-repetition maximum, n = 33), or control (passive stretching exercise, n = 36) for 6 weeks. All training sessions were supervised by trained instructors to minimize the risk of injury and to ensure that the participants adhered to the training protocol throughout the entire range of motion. The T-cell percentages and absolute blood counts were determined before and after 6 weeks (24 h-48 h after the last training session) using flow cytometry and a haematology analyser. Cytomegalovirus antibodies were measured in serum using Architect iSystem and cytomegalovirus serostatus was balanced in the three intervention groups. C-reactive protein was measured using immunonephelometry. RESULTS: We report for the first time that 6 weeks of strength endurance training significantly decreased senescence-prone T-cells along with a small increase in the number of CD8- naive T-cells in blood. The absolute counts of senescent-like T-cells decreased by 44% (from 26.03 ± 35.27 to 14.66 ± 21.36 cells/µL, p < 0.01) and by 51% (from 6.55 ± 12.37 to 3.18 ± 6.83 cells/µL, p < 0.05) for the CD8+ and CD8- T-cell pools, respectively. Intriguingly, these changes were observed in cytomegalovirus seropositive, but not cytomegalovirus seronegative individuals. CONCLUSIONS: In conclusion, the present study shows that strength endurance training leads to a reduction in circulating senescence-prone T-cells in cytomegalovirus seropositive older women. It remains to be established if monitoring of peripheral senescence-prone T-cells may have utility as cellular biomarkers of immunosenescence.

Convergent and concurrent validity of a report- versus performance-based evaluation of everyday functioning in the diagnosis of cognitive disorders in a geriatric population.

ABSTRACTBackground:Several methods have been developed to evaluate activities of daily living (ADLs) in mild cognitive impairment (MCI) and mild dementia. This study evaluated the convergent and concurrent validity between (1) two report-based methods (the advanced (a)- and instrumental (i)-ADL tools) and (2) a performance-based method (the Naturalistic Action Test (NAT)) to check if their ability to differentiate between cognitively healthy comparisons (HCs), persons with MCI, and persons with mild Alzheimer's disease (AD) are comparable to each other. METHOD: This was a cross-sectional study, undertaken in a geriatric day hospital. The participants comprised community-dwelling HCs (n = 21, median age 78.0 years, 61.9% female), MCI (n = 20, median age 79.5 years, 55.0% female), and AD (n = 20, median age 80.0 years, 85.0% female) adults. A diagnostic procedure for neurocognitive disorders was employed. In addition, the a- and i-ADL tools and the NAT were administered separately by blinded raters. RESULTS: The NAT and both the a- and i-ADL tools showed significant differences between HCs, MCI, and AD participants. Convergent validity showed moderate to strong significant correlations between the NAT, and a- and i-ADL tools (range -0.583 to -0.663; p < 0.01). Concurrent validity showed that the NAT (AUC 0.809-1.000) and the a- and i-ADL tools (AUC 0.739-0.964) presented comparable discriminatory accuracy (p = 0.0588). CONCLUSIONS: In contrast to prior studies comparing report-based and performance-based methods of assessing ADL, this study indicates that the NAT and the a- and i-ADL tools have strong convergent and concurrent validity, and appear to have similar discriminatory power in differentiating between HCs, MCI, and AD.

Early diagnosis of mild cognitive impairment and mild dementia through basic and instrumental activities of daily living: Development of a new evaluation tool.

BACKGROUND: Assessment of activities of daily living (ADL) is paramount to determine impairment in everyday functioning and to ensure accurate early diagnosis of neurocognitive disorders. Unfortunately, most common ADL tools are limited in their use in a diagnostic process. This study developed a new evaluation by adopting the items of the Katz Index (basic [b-] ADL) and Lawton Scale (instrumental [i-] ADL), defining them with the terminology of the International Classification of Human Functioning, Disability and Health (ICF), adding the scoring system of the ICF, and adding the possibility to identify underlying causes of limitations in ADL. METHODS AND FINDINGS: The construct validity, interrater reliability, and discriminative validity of this new evaluation were determined. From 2015 until 2016, older persons (65-93 y) with normal cognitive ageing (healthy comparison [HC]) (n = 79), mild cognitive impairment (MCI) (n = 73), and Alzheimer disease (AD) (n = 71) underwent a diagnostic procedure for neurocognitive disorders at the geriatric day hospital of the Universitair Ziekenhuis Brussel (Brussels, Belgium). Additionally, the ICF-based evaluation for b- and i-ADL was carried out. A global disability index (DI), a cognitive DI (CDI), and a physical DI (PDI) were calculated. The i-ADL-CDI showed high accuracy and higher discriminative power than the Lawton Scale in differentiating HC and MCI (area under the curve [AUC] = 0.895, 95% CI .840-.950, p = .002), MCI and AD (AUC = 0.805, 95% CI .805-.734, p = .010), and HC and AD (AUC = 0.990, 95% CI .978-1.000, p < .001). The b-ADL-DI showed significantly better discriminative accuracy than the Katz Index in differentiating HC and AD (AUC = 0.828, 95% CI .759-.897, p = .039). This study was conducted in a clinically relevant sample. However, heterogeneity between HC, MCI, and AD and the use of different methods of reporting ADL might limit this study. CONCLUSIONS: This evaluation of b- and i-ADL can contribute to the diagnostic differentiation between cognitively healthy ageing and neurocognitive disorders in older age. This evaluation provides more clarity and nuance in assessing everyday functioning by using an ICF-based terminology and scoring system. Also, the possibility to take underlying causes of limitations into account seems to be valuable since it is crucial to determine the extent to which cognitive decline is responsible for functional impairment in diagnosing neurocognitive disorders. Though further prospective validation is still required, the i-ADL-CDI might be useful in clinical practice since it identifies impairment in i-ADL exclusively because of cognitive limitations.

The effects of exercise on muscle strength, body composition, physical functioning and the inflammatory profile of older adults: a systematic review.

PURPOSE OF REVIEW: This systematic review reports the most recent literature regarding the effects of physical exercise on muscle strength, body composition, physical functioning and inflammation in older adults. All articles were assessed for methodological quality and where possible effect size was calculated. RECENT FINDINGS: Thirty-four articles were included - four involving frail, 24 healthy and five older adults with a specific disease. One reported on both frail and nonfrail patients. Several types of exercise were used: resistance training, aerobic training, combined resistance training and aerobic training and others. In frail older persons, moderate-to-large beneficial exercise effects were noted on inflammation, muscle strength and physical functioning. In healthy older persons, effects of resistance training (most frequently investigated) on inflammation or muscle strength can be influenced by the exercise modalities (intensity and rest interval between sets). Muscle strength seemed the most frequently used outcome measure, with moderate-to-large effects obtained regardless the exercise intervention studied. Similar effects were found in patients with specific diseases. SUMMARY: Exercise has moderate-to-large effects on muscle strength, body composition, physical functioning and inflammation in older adults. Future studies should focus on the influence of specific exercise modalities and target the frail population more.

Effects of resistance training at different loads on inflammatory markers in young adults.

PURPOSE: Suppressing inflammaging at an early stage in life via exercise might prevent chronic diseases later in life. The aim was to investigate the influence of resistance training at different external loads on inflammatory markers in healthy young adults. METHODS: Serum was collected for basal levels of cytokines (IL-1beta, IL-6, IL-8, sTNFR1, IL-1RA, IL-10 and GM-CSF) before and after 9 weeks exercise from 36 young (22 ± 2 years) healthy subjects who were randomized to three times weekly supervised resistance training at either HImax (n = 12, 1 × 10-12 repetitions at 80% 1RM), LO (n = 12, 1 × 10-12 repetitions at 40% 1RM), or LOmax (n = 12, 1 × 10-12 repetitions at 40% 1RM preceded by 60 repetitions at 20-25% 1RM) respectively. RESULTS: Overall, IL-8 increased (p < 0.001) and IL-6 decreased (p = 0.001) after training, but no significant time*group interaction was found (respectively, p = 0.283 and p = 0.058 for IL-8 and IL-6). When analyzed separately, IL-8 increased significantly in HImax (p = 0.022) and LOmax (p = 0.024); and IL-6 decreased significantly in LOmax (p = 0.009) and LO (p = 0.013). No significant overall time effect was observed for sTNFR1 and IL-1RA; however, in HImax sTNFR1 (p = 0.031) and IL-1RA (p = 0.014) increased significantly, but remained unchanged in LOmax and LO. IL-1beta, IL-10 and GM-CSF levels remained undetectable in most participants. CONCLUSIONS: Nine weeks of resistance training-irrespective of the external load-have beneficial effects on circulating IL-8 and IL-6. In addition, training at high external load increases the anti-inflammatory cytokines sTNFR1 and IL-1RA. The results of this study show that resistance training has anti-inflammatory effects in healthy young persons and that the response of the different inflammatory mediators depends on the magnitude of the external load.

Fall predictors in older cancer patients: a multicenter prospective study.

BACKGROUND: In the older population falls are a common problem and a major cause of morbidity, mortality and functional decline. The etiology is often multifactorial making the identification of fall predictors essential for preventive measures. Despite this knowledge, data on falls within the older cancer population are limited. The objective of this study was to evaluate the occurrence of falls within 2 to 3 months after cancer treatment decision and to identify predictors of falls (≥1 fall) during follow-up. METHODS: Older patients (70 years or more) with a cancer treatment decision were included. At baseline, all patients underwent geriatric screening (G8 and Flemish Triage Risk Screening Tool), followed by a geriatric assessment including living situation, activities of daily living (ADL), instrumental activities of daily living (IADL), fall history in the past 12 months, fatigue, cognition, depression, nutrition, comorbidities and polypharmacy. Questionnaires were used to collect follow-up (2-3 months) data. Univariate and multivariate analyses were performed to identify predictors for falls (≥1 fall) during follow-up. RESULTS: At baseline, 295 (31.5%) of 937 included patients reported at least one fall in the past 12 months with 88 patients (29.5%) sustaining a major injury. During follow-up (2-3 months), 142 (17.6%) patients fell, of whom 51.4% fell recurrently and 17.6% reported a major injury. Baseline fall history in the past 12 months (OR = 3.926), fatigue (OR = 0.380), ADL dependency (OR = 0.492), geriatric risk profile by G8 (OR = 0.471) and living alone (OR = 1.631) were independent predictors of falls (≥1 fall) within 2-3 months after cancer treatment decision. CONCLUSION: Falls are a serious problem among older cancer patients. Geriatric screening and assessment data can identify patients at risk for a fall. A patient with risk factors associated with falls should undergo further evaluation and intervention to prevent potentially injurious fall incidents.

The relationship between self-perceived fatigue, muscle endurance, and circulating markers of inflammation in participants of the Copenhagen aging and Midlife Biobank (CAMB).

BACKGROUND: Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife. METHODS: A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions). RESULTS: Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015). CONCLUSIONS: Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.

Chronic low-grade inflammation and age-related sarcopenia.

PURPOSE OF REVIEW: Age-related chronic low-grade inflammatory profile (CLIP) has been recognized as an important causative factor for sarcopenia. Here, we report the recent evidence concerning CLIP and sarcopenia. RECENT FINDINGS: Twenty-one studies were included (12 observational, five interventional studies and four randomized controlled trials). Observational studies strengthen the association between CLIP and sarcopenia in cross-sectional and longitudinal designs. Interleukin (IL)-6 and tumour necrosis factor-α are the most reported inflammatory parameters. Biopsy studies confirm the role of oxidative mechanisms, protein kinase B and nuclear factor kappa-light-chain-enhancer of activated B cells pathways and implicate stress response mechanisms and heat shock protein. Adipose tissue as source of inflammatory cytokines remains unclear and correction for fat mass is advisable in new research. Exercise interventions (both aerobic and resistance training) demonstrate beneficial effects on CLIP even in the absence of decreases in weight, BMI or fat mass. IL-6 is also released during exercise, in hormone-like fashion unrelated to inflammation, and exercise-induced IL-6 changes require careful interpretation. Soy supplementation in one study showed no influence on CLIP and no recent pharmacological trials were retrieved. SUMMARY: Associations between CLIP and sarcopenia are observed quite consistently and underlying mechanisms become apparent. Exercise remains the mainstay intervention to lower CLIP and counter sarcopenia. More research is warranted to unravel the exact dose-response relationship.

Three Months of Strength Training Changes the Gene Expression of Inflammation-Related Genes in PBMC of Older Women: A Randomized Controlled Trial.

Here, we investigate changes in inflammation-related gene-expression in peripheral mononuclear blood cells (PBMC) by strength training. A total of 14 women aged ≥65 years were randomized into 3 months of either 3×/week intensive strength training (IST: 3×10 rep at 80% 1RM), strength endurance training (SET: 2×30 reps at 40% 1RM) or control (CON: 3×30 sec stretching). Differentially expressed genes (fold change ≤0.67 or ≥1.5) were identified by targeted RNA-sequencing of 407 inflammation-related genes. A total of 98 genes (n = 61 pro-inflammatory) were significantly affected. IST and SET altered 14 genes in a similar direction and 19 genes in the opposite direction. Compared to CON, IST changed the expression of 6 genes in the same direction, and 17 genes in the SET. Likewise, 18 and 13 genes were oppositely expressed for, respectively, IST and SET compared to CON. Changes in gene expression affected 33 canonical pathways related to chronic inflammation. None of the altered pathways overlapped between IST and SET. Liver X Receptor/Retinoid X Receptor Activation (LXR/RXR) and Triggering Receptor Expressed On Myeloid Cells 1 (TREM1) pathways were enriched oppositely in both training groups. We conclude that three months IST and SET can induce changes in CLIP-related gene expression in PBMC, but by affecting different genes and related pathways.

Reporting of Palliative Sedation and Use of Opioids at the End of Life in a Belgian University Hospital: A Pilot Study.

Background: Palliative sedation requires no formal registration in Belgium. For euthanasia, however, there are clear guidelines in certain countries, including mandatory registration and evaluation of cases. Official guidelines have been developed for palliative sedation, but research still shows unskilled use of sedation and unclear demarcation between palliative sedation and euthanasia. Registration could be used to avoid unskilled use of sedation and to avoid use or abuse of sedation to hasten the patient's death (described as "slow/passive euthanasia"). Objective: To evaluate the current practice of palliative sedation and use of opioids and sedatives at the end of life by using a registration document. Design: Retrospective observational study. Setting/Subjects: We included all in-hospital deaths at an academic hospital in Belgium of patients (age ≥18 years) who had received parenteral opioids, benzodiazepines, barbiturates, or other anesthetics during the last 24 hours. Measurements: We investigated indications for palliative sedation, patients' and physicians' characteristics, types of medication used, and the decision-making process with the patients and family. The questionnaires were collected between July 9 and November 25, 2016. The study was approved by the Biomedical Ethics Committee of UZ Brussel (B.U.N. 1432016293). Results: In a population of 124 patients, refractory symptoms were reported in 94.4%. All patients received parenteral opioids (intravenously). Benzodiazepines were used in 51.6%. In 75.8%, physicians reported no change in treatment plan during end of life. Hastening death by increasing analgesics and/or sedatives was mentioned in 19.3%. The treatment plan was discussed with patients in 26.6% of cases. In 6 cases, an explicit intention to hasten death was mentioned; in 36 cases, doses of opioids/sedatives may not have been strictly proportional to symptoms. Conclusion: This Belgian study shows that objective reporting of palliative sedation can be used as a tool to ensure good clinical practice where patients receive the most appropriate end-of-life care, avoiding abusive and injudicious or unskilled use of sedation.

Audiometric Findings in Senior Adults of 80 Years and Older.

Objective: To examine hearing thresholds in senior adults of 80 years and older and compare this data to the current ISO 7029 reference values. Design: A descriptive, prospective study testing pure-tone and speech audiometry in senior adults participating in the BUTTERFLY study or the BrUssels sTudy on The Early pRedictors of FraiLtY. A Gerontological study to identify determinants for active aging and for early stages of frailty in the oldest population. Using the formula given by ISO 7028:2017 the median value of hearing was calculated based on the sex and age of the participant and compared to the measured hearing thresholds. Results: 151 senior adults were included. The prevalence of hearing loss was 90.7% (PTA > 20 dB HL). The results were compared to the mean ISO values, calculated for every participant. Both males and females in our study population had worse hearing thresholds than could be expected based on the ISO reference values. In our study population with moderate hearing loss (PTA > 40 dB HL), 38% is underserved in term of hearing restoration healthcare and yet another 38% is unsatisfied with the result of the hearing aids. Given the vast impact on the individual and society, this is a problem in need of our attention. Conclusion: The ISO 7029 reference values may be an underestimation of hearing loss in senior adults of 80 years and older. Therefore we present a statistical distribution of hearing thresholds on different frequencies related to age and sex that can be used as a baseline for further development of the reference values.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN96340690.

The effects of exercise interventions on the inflammatory profile of older adults: A systematic review of the recent literature.

INTRODUCTION: Inflammageing - characterized by age-related chronic low-grade inflammation is considered to be positively influenced by physical exercises. The aim of this systematic review is to provide an update of the most recent literature regarding exercise effects on the inflammatory profile in older adults. METHODS: This review is an update of an earlier published literature review and was performed according to the NICE guidelines. Databases PubMed and Web-of-Science were systematically searched by two independent authors screening for papers published since 2016. Effect sizes of outcome parameters related to the inflammatory profile were calculated where possible. RESULTS & DISCUSSION: Twenty-three articles were included. Resistance training (RT) was the most investigated type of exercise (13 articles: 8 in healthy, 1 in frail and 4 in older adults with a specific condition or disease). Aerobic training (AT) was investigated in 8 articles, including 5 studies in older adults with a specific disease or condition. Combined resistance & aerobic training (CT) was investigated in 7 articles: 3 were in healthy, 1 in frail and 3 in older adults with a specific condition or disease. 1 study investigated the effects of Tai Chi in older adults with mild cognitive impairment. In frail older subjects, IGF-1 - sole marker investigated - significantly increased after 8 weeks RT and CT, whereas AT showed no significant effects compared to control. Most consistent exercise effects consisted in lowering of circulating levels of CRP, IL-6 and TNF-α; which seemed more prominent in healthy older adults compared to those with a specific disease or condition. None of the studies reported an exacerbation of inflammation following exercise and all studied exercise protocols were feasible and safe for older adults. CONCLUSIONS: Overall, significant anti-inflammatory effects of exercise in older persons were reported. Literature remains extremely scarce regarding the exercise-induced effects in frail older persons. Therefore, there is an urgent need for more studies focusing on the frail elderly. There is growing literature data on exercise interventions in older adults with a specific condition or disease; however, it appears more challenging to reduce inflammageing through exercise in these specific patient groups. Importantly, the exercise interventions performed in all studies appeared to be feasible and safe for older patients, thus the presence of a specific condition or disease should not be considered as a contra-indication to perform physical exercise.

Effect of Antihypertensive and Statin Medication Use on Muscle Performance in Community-Dwelling Older Adults Performing Strength Training.

OBJECTIVES: Antihypertensive drugs (AHTD) and statins have been shown to have effects beyond their primarily designed purpose; here we investigate their possible effect on muscle performance and strength in older adults following a physical exercise programme. DESIGN: The Senior PRoject INtensive Training (SPRINT) study is a randomised, controlled clinical trial designed to evaluate the effects of physical exercise on the immune system and muscle performance in older adults. PARTICIPANTS: In this secondary analysis, we included 179 independent participants (aged 65 years and above). We applied further categorisation based on medication use: AHTD (including, angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARB], ß-blockers, and other AHTD) and statins. INTERVENTION: Participants were allocated randomly to one of the three exercise protocols: intensive strength training 3 times/week (3 × 10 repetitions at 80% of one-repetition maximum), strength endurance training (2 × 30 repetitions at 40% of one-repetition maximum), or control (passive stretching exercise) for 6 weeks. MEASUREMENTS: The change in maximal hand grip strength (GS), muscle fatigue resistance (FR), Muscle Strength Index (MSI), the 6-min walk test (6MWT), and Timed Up and Go Test (TUG) were assessed before and after 6 weeks of training. RESULTS: After 6 weeks, muscle strength (MSI and TUG) improved significantly in all training groups compared to baseline, independently of AHTD use. Moreover, AHTD had no effect on exercise improvements, with no significant differences between medication groups, except for TUG in ARB users, which exhibited a significantly lower performance. On the other hand, statin users presented a significantly longer FR time, indicating better performance compared to non-users. Finally, medication did not affect the participants' commitment to the training programme. CONCLUSION: Our study showed that statins and ARB usage might affect participant's response to strength training. Nevertheless, 6 weeks of training significantly improved muscle strength and performance irrespective of AHTD or statin use.

Muscle fatigability measured with Pneumatic and Hydraulic handgrip systems are not interchangeable.

BACKGROUND: Fatigue resistance (FR) was here defined as the time during which grip strength (GS) drops to 50% of its maximum during sustained contraction. Since different GS systems exist, we compared FR obtained with Pneumatic (Pneu) and Hydraulic (Hydr) handgrip systems. Hand pain induced by both systems was also investigated since this might influence FR-outcomes. METHODS: 618 young controls (Y: reference group), 426 middle-aged (MA) and 234 old community-dwelling adults (OLD), and 50 hospitalized patients (HOSP) participated. FR was recorded with Pneu and Hydr. Grip work corrected for body weight (area under the strength-time curve; GWBW = 0.75 ∗ maximal GS ∗ FR / body weight) was calculated. We corrected for body weight since heavier or more obese participants will have to engage more strength and sustain the effort over time. Thereafter GWBW was expressed as T-scores representing the deviation from the mean score of the sex-specific reference group. Experienced pain, its intensity and whether pain hindered participants to sustain the contraction were questioned. RESULTS: Overall, although significant correlation between FR measured with both systems was found (r = 0.418, p < 0.001), FR measured by Pneu (55.7 ± 35.0 s) was higher compared to Hydr (34.2 ± 18.4 s). There was a proportional difference in FR measured with both systems (R2 = 0.36, p < 0.001), highlighting the longer participants could sustain FR test, the higher the difference in FR measured with both systems. Overall, there was no difference in pain variables between both systems. Independent of sex and system, GWBW deviated less from reference group in MA compared to OLD and HOSP. In OLD, GWBW deviated less from reference group than HOSP, independent of sex and system. CONCLUSION: Participants were unable to sustain the contraction with Hydr as long as with Pneu. Hydr seems less able to identify subjects with higher levels of muscle endurance. Based on the GWBM-scores we can conclude that either system can be used for assessing muscle fatigability, but Pneu may be more sensitive as differences can be detected more easily.

Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role?

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty. One hundred seventy-three persons aged 80 to 99 years were enrolled. Pre-frailty was defined according to Fried's criteria. Anti-CMV IgG and serum IL-6 were measured using Architect iSystem and Luminex, respectively. T-cell phenotypes were determined using flow cytometry. The prevalence of pre-frailty was 52.6%, increased with age (p = .001), and was greater in men than women (p = .044). No relationship was found between pre-frailty and positive CMV serology. Further, CMV-seropositivity was significantly associated with less naïve cells, more memory and senescence-prone phenotypes (all p < .001). After adjusting for potential confounders, only IL-6, age and sex were predictive of pre-frailty. We conclude that the presence of pre-frailty is independent from CMV infection in very old subjects.

Strength Endurance Training but Not Intensive Strength Training Reduces Senescence-Prone T Cells in Peripheral Blood in Community-Dwelling Elderly Women.

Aging is characterized by a progressive decline in immune function known as immunosenescence. Although the causes of immunosenescence are likely to be multifactorial, an age-associated accumulation of senescent T cells and decreased naive T-cell repertoire are key contributors to the phenomenon. On the other hand, there is a growing consensus that physical exercise may improve immune response in aging. However, the optimum training modality required to obtain beneficial adaptations in older subjects is lacking. Therefore, we aimed to investigate the effects of exercise modality on T-cell phenotypes in older women. A total of 100 women (aged ≥ 65 years) were randomized to either intensive strength training (80% of one-repetition maximum ), strength endurance training (40% one-repetition maximum), or control (stretching exercise) for 2-3 times per week during 6 weeks. The T-cell percentages and absolute counts were determined using flow cytometry and a hematology analyzer. C-reactive protein was measured using immunonephelometry. We report for the first time that 6 weeks of strength endurance training significantly decreased the basal percentage and absolute counts of senescence-prone T cells, which was positively related to the number of training sessions performed. Conceivably, training protocols with many repetitions-at a sufficiently high external resistance-might assist the reduction of senescence-prone T cells in older women.