Ingo Beyer

Chronic low-grade inflammation and age-related sarcopenia.

Purpose of reviewAge-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 findingsTwenty-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-&agr; 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. SummaryAssociations 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.

Clinical Relevance of Thiamine Status amongst Hospitalized Elderly Patients

Background: The prevalence and the consequences of thiamine deficiency among elderly patients admitted to acute geriatric wards are not known. Objectives: (1) To assess the prevalence of thiamine deficiency in patients admitted to a geriatric ward compared to age-matched ambulatory outpatients; (2) to identify their diseases and problems associated with thiamine deficiency, and (3) to determine the relationship between the thiamine status and the cognitive and functional status of these patients. Materials and Methods: 118 aged hospitalized patients (83 ± 7 years; mean age ± SD) were prospectively enrolled on admission to the geriatric ward. Their cognitive status was assessed using the Mini-Mental State Examination (MMSE) and their ability to perform their activities of daily living (ADL) using ADL scales. The effect of exogenous thiamine pyrophosphate (TPP) addition on the blood transketolase (TK) activity (TPP TK effect) served to estimate thiamine deficiency. Socioeconomic data, diseases and treatment were identified as potential associated risk factors. This group of hospitalized patients was divided according to their thiamine status to characterize the conditions associated with thiamine deficiency. Thirty-five outpatients without any functional or cognitive impairment served as a control group. Results: Of 118 inpatients, 46 (39%) presented with a TPP TK effect of >15%, and 6 with values of >22%, indicating moderate and severe thiamine deficiency, respectively. Only 6 of 30 outpatients (20%) exhibited a TPP TK effect of >15% and none of them reached values of >18%. Although it tended to be lower in outpatients, the mean TPP TK effect did not statistically differ from the mean of inpatients. Thiamine-deficient inpatients comprised a larger proportion of institutionalized subjects than nondeficient inpatients (87 versus 47%, p < 0.001). Functional status, cognitive functions and the occurrence of delirium did not differ according to their thiamine status. By contrast, thiamine-deficient inpatients exhibited a higher proportion of Alzheimer’s disease, depression, cardiac failure and falls. Furosemide was more frequently taken by thiamine-deficient patients. Conclusions: Severe thiamine deficiency remained quite low among the hospitalized elderly. The prevalence of moderate thiamine deficiency approached 40%. Institutionalized subjects were at particular risk of developing thiamine deficiency. Its clinical relevance on functional status and on cognitive function remained not significant. By contrast, a high proportion of falls, Alzheimer’s disease, depression, cardiac failure and furosemide use could have been related to thiamine deficiency.

Effect of advanced glycation end product intake on inflammation and aging: a systematic review

Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health.

Inflammation-related muscle weakness and fatigue in geriatric patients.

Inflammation in older persons is associated with muscle wasting, leading to frailty and functional decline. Most studies have focused on IL-6 and TNF-α. In order to further elucidate the underlying mechanisms of muscle wasting and reduced muscle mass and strength we investigated a large panel of cytokines and chemokines, as well as cytoprotective heat shock proteins (Hsp), and measured lean body mass (LBM) and grip strength (GS), fatigue resistance (FR), and grip work (GW) in 33 geriatric patients (median age 84 years) admitted with acute infection-induced inflammation. Higher expression of Hsp27 without heat challenge (WHC) in circulating monocytes and lymphocytes correlated with better FR (r=0.363, p<0.05 and r=0.602, p<0.001 respectively) suggesting a protective effect, as Hsp27 is abundant in muscle. On the other hand, higher serum levels of the inflammatory chemokines CCL11/Eotaxin and CCL2/MCP-1 were related to lower GS and lower LBM (r=-0.393, p<0.05; r=-0.431, p<0.05) respectively. Our results point to a complex pattern of pro-and anti-inflammatory substances that interact with skeletal muscle performance during acute inflammation.

Frailty and the Prediction of Negative Health Outcomes: A Meta-Analysis

INTRODUCTION Frailty is one of the most important concerns regarding our aging population. Evidence grows that the syndrome is linked to several important health outcomes. A general overview of frailty concepts and a comprehensive meta-analysis of their relation with negative health outcomes still lacks in literature, making it difficult for health care professionals and researchers to recognize frailty and the related health risks on the one hand and on the other hand to appropriately follow up the frailty process and take substantiated action. Therefore, this study aims to give an overview of the predictive value of the main frailty concepts for negative health outcomes in community-dwelling older adults. METHODS This review and meta-analysis assembles prospective studies regarding the relation between frailty and any potential health outcome. Frailty instruments were subdivided into frailty concepts, so as to make comprehensive comparisons. Odds ratios (ORs), hazard ratios (HRs), and relative risk (RR) scores were extracted from the studies, and meta-analyses were conducted in OpenMeta Analyst software. RESULTS In total, 31 articles retrieved from PubMed, Web of Knowledge, and PsycInfo provided sufficient information for the systematic review and meta-analysis. Overall, (pre)frailty increased the likelihood for developing negative health outcomes; for example, premature mortality (OR 2.34 [1.77-3.09]; HR/RR 1.83 [1.68-1.98]), hospitalization (OR 1.82 [1.53-2.15]; HR/RR 1.18 [1.10-1.28]), or the development of disabilities in basic activities of daily living (OR 2.05 [1.73-2.44]); HR/RR 1.62 [1.50-1.76]). CONCLUSION Overall, frailty increases the risk for developing any discussed negative health outcome, with a 1.8- to 2.3-fold risk for mortality; a 1.6- to 2.0-fold risk for loss of activities of daily living; 1.2- to 1.8-fold risk for hospitalization; 1.5- to 2.6-fold risk for physical limitation; and a 1.2- to 2.8-fold risk for falls and fractures. The analyses presented in this study can be used as a guideline for the prediction of negative outcomes according to the frailty concept used, as well as to estimate the time frame within which these events can be expected to occur.

Management of urinary tract infections in the elderly

Summary Urinary tract infection (UTI) is the most common infection and the first cause of bacteremia in the elderly. With increasing age the female to male ratio decreases and UTI becomes almost half as frequent in men compared to women. Significant bacteriuria exists in about 40% of institutionalized women. But asymptomatic bacteriuria is neither the cause of morbidity nor associated with a higher mortality rate and thus should not be treated. Symptomatic infection in women without complicating factors is most often caused by E. coli and may be treated with 3 or 7 day regimens of trimethoprim-sulfamethoxazole or fluoroquinolones (FQ). In the presence of symptoms of upper tract infection or complicating factors, urine culture is mandatory and will detect multiple and/or resistant microorganisms in most cases. Empirical treatment has to be adapted according to the sensitivity once established and should be administered for at least 10 days. Most of the patients above 65 and virtually all patients above 80 present either with general debility or diabetes or other factors such as bladder outflow obstruction or abnormal bladder function and have to be considered as presenting with complicated UTI. Indwelling catheters should be removed if possible, otherwise be changed.Zusammenfassung Harnwegsinfektionen (HWI) sind die häufigsten Infektionen und die vorrangige Ursache für Bakteriämien bei älteren Menschen. Mit zunehmendem Alter nimmt die Proportion der HWI bei Männern im Verhältnis zu Frauen zu und die HWI wird beim Mann beinahe halb so häufig wie bei der Frau. Eine bedeutsame Bakteriurie besteht bei ungefähr 40% der institutionalisierten Frauen. Aber asymptomatische HWI sind weder die Ursache für Morbidität noch mit einer erhöhten Mortalität verbunden und sollten deshalb nicht behandelt werden. Symptomatische Infektionen bei Frauen ohne Komplikationsfaktoren werden in den meisten Fällen von E. coli verursacht und können 3 oder 7 Tage lang mit Antibiotika wie Trimethoprim-Sulfamethoxazol oder Fluoroquinolonen in geringer Dosis behandelt werden. Sobald Symptome einer Niereninfektion oder Komplikationsfaktoren vorliegen, ist eine Urinkultur unabkömmlich und diese weist in den meisten Fällen mehrfache und/oder resistente Krankheitserreger nach. Empirische Behandlungen müssen dann dem Sensibilitätsspektrum entsprechend angepasst werden, und sollten für mindestens 10 Tage verabreicht werden. Die meisten Patienten über 65 und sozusagen alle Patienten über 80 haben entweder eine allgemeine Schwäche oder Diabetes oder andere Faktoren wie anormale Blasenfunktion oder Blasenabflussstörungen und sollten deshalb für komplizierte HWI behandelt werden. Dauerkatheter sollten wenn möglich entfernt oder zumindest gewechselt werden.

Prevalence of orthostatic hypotension and relationship with drug use amongst older patients

Abstract Introduction: Orthostatic hypotension (OH) is said to be highly prevalent in older people. Drugs are often involved as causative factor. Nevertheless, few data are available about the prevalence of OH and its relationship with drugs in olders. Objectives: To review data about (i) the prevalence and characteristics of OH in older patients; and (ii) the relationship between OH and drugs. Methods: Review of publications from Ovid (Pub-Med) from 1980 to May 2011 using the following key words: “orthostatic hypotension” combined with “elderly” or equivalent for the analysis of prevalence (first search) and “orthostatic hypotension” combined with “drugs” or equivalent to assess the relationship between OH and drugs (second search). Results: Fifty-one publications (of which 14 with original data) were retrieved from the prevalence search, 31 for the second search (8 with original data: 7 retrospective studies and 1 prospective cohort study) and 12 reviews or experts opinions. Prevalence of OH varies according to the characteristics of the subjects, the settings of the studies, and the procedures of blood pressure measurement. In acute geriatrics units, two studies reported a prevalence of over 30% and one study mentioned that 68% of the patients presented with at least one episode during the day. OH was associated with several geriatric problems: gait disorders, balance disorders, falls, cerebral hypoperfusion, transient ischemic attacks, cognitive impairment, acute myocardial infarct and systolic hypertension. OH can also be asymptomatic or with atypical presentation: falls, gait disorders and confusion. Psychotropic agents (antipsychotics, sedatives, antidepressants), and cardiovascular drugs (antihypertensive agents, vasodilators, diuretics) were associated with OH. Discussion: If the hypothesis of causality between drug treatment and OH is confirmed, the identification of the involved drugs could be of value for the prevention of OH and its complications. In this context, the Working Group Pharmacology Pharmacotherapy and Pharmaceutical Care of the Belgian Society of Gerontology and Geriatrics proposes to conduct a multicentre study to assess the prevalence of OH in Belgian acute geriatrics units and its relationship with drugs.

Anemia and transfusions in geriatric patients: a time for evaluation

Abstract Anemia is common in the elderly, especially in very old patients who are often frail and may be institutionalized. Senescence, the ageing process, puts the elderly at risk of developing anemia for multiple reasons, but anemia may not be attributed to senescence unless a thorough diagnostic workup has excluded other etiologies. Nutritional deficiencies are common and need to be identified and treated appropriately. Inflammatory diseases and renal failure are also frequent etiological factors and tend to be chronic. Myelodysplastic syndromes increase in frequency with age and may be difficult to diagnose and only a minority of cases respond to appropriate treatment. Anemia is associated with poor outcome and symptomatic treatment with transfusions frequently has to be considered. Red blood cell transfusion has a high therapeutic index and is likely to be effective only if anemia is symptomatic or particularly severe, as a consequence, its use has been restricted to this group. Much of the evidence on usage is limited to younger adults and specific clinical situations. Geriatricians have to deal with a large number of patients with significant anemia but with an absence of well constructed guidelines for the frail and the very old. The object of the present article is to raise awareness that anemia in the geriatric group is multi-factorial and that the patients are more than merely older than those included in most studies, that the results of ongoing trials should be appropriately interpreted and will be important in guiding future practice.

Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults.

BACKGROUND BDNF is known to induce neuroplasticity and low circulating levels have been related to neuronal loss in older persons. Physical exercise is thought to trigger BDNF-induced neuroplasticity, but conflicting observations have been reported regarding the effects of resistance training on circulating BDNF in the elderly. These conflicting observations might reflect dose-and gender-specific differences. METHOD Fifty-six apparently healthy elderly (68 ± 5 years) participants were randomized to 12 weeks of resistance training (3×/week) at either high-resistance (HIGH, 8 Males, 10 Females, 2 × 10-15 repetitions at 80% 1 RM), low-resistance (LOW, 9 Males, 10 Females, 1 × 80-100 repetitions at 20% 1 RM), or mixed low-resistance (LOW+, 9 Males, 10 Females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10-20 repetitions at 40% 1 RM). Serum was collected for BDNF assay at baseline and after 12 weeks (24 h-48 h after the last training). RESULTS 12 weeks of LOW+ exercise significantly increased BDNF levels in male (from 34.9 ± 10.7 ng/mL to 42.9 ± 11.9 ng/mL, time × group interaction p=0.013), but not in female participants. No significant change was observed in HIGH or LOW, neither in male nor female subjects. CONCLUSION Our results show that only the mixed-low-resistance training program with a very high number of repetitions at a sufficiently high external resistance was able to increase circulating BDNF in older male participants. Training to volitional fatigue might be necessary to obtain optimal results. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed gender difference.

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

BackgroundInflammation 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.MethodsConsecutive 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.ResultsEMS 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.ConclusionsPiroxicam 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 numberISRCTN: ISRCTN96340690