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Background and Purpose: Cutoff points for physical function tests are commonly used in clinical practice for the evaluation, monitoring, and treatment of older adults. Previous studies have shown that, while age-related patterns of muscle strength change are similar between ethnic groups, strength values differ significantly independent of age. Whether the same applies to other physical function tests is presently unclear. This study investigated age- and gender-related changes of performance on a battery of physical function tests in Brazilian community dwellers. Methods: The study followed a cross-sectional design. Participants were community-dwelling adults. Candidates were considered eligible if they were 18 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all of the measurements required by the protocol. Physical function tests included isometric handgrip (IHG), 5 times sit-to-stand (5×STS) test, Timed Up and Go, 1-leg stance, and walking speed (WS) at usual and fast pace. Results: Two-thousand eight-hundred and four people were enrolled. Mean age was 68.0 (7.0) years (range 50-102 years), and 2262 (80.7%) were women. Men displayed better IHG and balance, while women showed higher performance on the 5×STS and WS tests. A gender-specific pattern of decline in physical performance was observed. Specifically, women showed a linear age-dependent decline in all tests. In men, only in the IHG, 1-leg stance, and WS test at a fast pace was there a linear decline with age. In both genders, the lowest mean values of physical function tests were higher than the proposed cutoffs for sarcopenia. Discussion and Conclusions: Our findings indicate that the performance on different physical function tests decreases with advancing age in Brazilian adults, following a gender-specific pattern. In none of the tests did the lowest mean values reach the cutoffs for sarcopenia. This suggests that region-specific cutoffs might be

Background: Frailty is increasingly reported among older adults with cardiovascular diseases and it has been demonstrated to increase negative health outcomes and mortality. To date, no systematic review of the evidence is available regarding the association between frailty and ischemic heart disease (IHD). We performed a systematic review of literature and a meta-analysis to assess the association between frailty and IHD. Methods: We selected all the studies that provided information on the association between frailty and IHD, regardless of the study setting, study design, or definition of IHD and frailty. PubMed, Web of Science and Embase were searched for relevant papers. Studies that adopted the Fried definition for frailty were included in the meta-analyses. For each measure of interest (proportions and estimates of associations), a meta-analysis was performed if at least three studies used the same definition of frailty. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Results: Thirty-seven studies were included. Of these, 22 adopted the Fried criteria to define frailty and provided estimates of prevalence and therefore they were included in meta-analyses. The pooled prevalence of IHD in frail individuals was 17% (95% Confidence Interval [95%CI] 11-23%) and the pooled prevalence of frailty in individuals with IHD was 19% (95% CI 15-24%). The prevalence of frailty among IHD patients ranged from 4 to 61%. Insufficient data were found to assess longitudinal association between frailty and IHD. Conclusions: Frailty is quite common in older persons with IHD. The identification of frailty among older adults with IHD should be considered relevant to provide individualized strategies of cardiovascular prevention and care. Further research should specifically explore the association between frailty and IHD and investigate the potential common biological ground.

Background: Bloodstream infections (BSIs) are a major cause of mortality in elderly. Objective of the study is to identify factors predictive of mortality in old and oldest old patients. Methods: This is a single centre retrospective observational study, including all patients admitted to Fondazione Policlinico A. Gemelli university hospital and diagnosed with BSI. Patients were stratified into three groups according to age: adult (A), younger than 65; old (O), aged between 65 and 80; oldest old (OO), older than 80. Primary outcome was 30-day in-hospital mortality. Secondary outcomes were duration of antimicrobial therapy (DOT) and length of hospital stay (LOS). Results: Of the 1034 patients included in the study, 346 were in group A, 447 in group O and 241 in group OO. The rate of 30-day mortality raised from 6.9% (24/346) in group A to 10.8% (84/447) in group O and 33.2% (80/241) in group OO (p<0.01), while DOT and LOS significantly decreased moving from adults to oldest old (p<0.01). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus spp were both independently correlated to an increased 30-day mortality risk selectively in patients older than 80 (MRSA: HR 2.37, p=0.03; Enterococcus spp: HR 2.44, p=0.01). Conclusions: BSIs have a high impact on survival in old and oldest old patients. BSIs by gram-positive pathogens, in particular MRSA and Enterococcus spp, should be a wake-up call for physicians, who should focus efforts on adequate and prompt antibiotic and support treatment.

Objectives: To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson’s disease (PD). Methods: 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers’ and patients’ characteristics on the varying aspects of burden. Results: ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases. Discussion: An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient’s global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

Background: Late-life depression is common among older adults living in nursing homes (NHs). Over the last 30 years there has been an increase in the rates of prescription of antidepressant medications across all ages, with the largest rise reported in older adults. This study aimed to describe the pattern of antidepressant medication use among NH residents from 7 European countries and Israel and to examine patient and facilities characteristics that may account for it. Methods: We conducted a cross-sectional analysis of data from the SHELTER study, an observational longitudinal cohort study that collected comprehensive resident data using the interRAI Long-Term Care Facility instrument in 7 European Countries and Israel. Descriptive statistics were used to examine sample characteristics. Potential correlates of antidepressant medication use were identified using multiple logistic regression modeling. Results: Among 4023 residents entering the study, 32% had depressive symptoms and nearly half of these individuals used antidepressants. Antidepressant medication use varied by country, with a prevalence in the overall sample of 35.6% (n = 1431). Among antidepressant users, 59.9% were receiving selective serotonin reuptake inhibitors (SSRI). The strongest correlates of antidepressant use included reported diagnosis of anxiety, depression, bipolar disorder, pain, falls and high level of social engagement. Age over 85 years, living in facilities located in rural areas and a diagnosis of schizophrenia reduced the likelihood of being prescribed with an antidepressant. Conclusions: A large proportion of residents in European long-term care facilities receive antidepressant medications. The decision to prescribe antidepressants to NH residents seems to be influenced by both patient and facility characteristics. Future longitudinal studies should evaluate the efficacy and safety of antidepressant use in NHs thus providing evidence for recommendations for clinical practice.

We evaluated patients admitted through our ED for community-acquired pneumonia (CAP) to assess the relevance of an early procalcitonin (PCT) determination on patient's outcomes. Methods: We reviewed all patients admitted for CAP in a 10 years period (2008-2017). Patients were stratified according to age groups: (18-65 years; 65-84 years; and ≥85 years), CURB-65 score, need for ventilation, Sepsis-3 criteria at admission, enrollment period, blood culture in ED. In-hospital mortality rate and length of hospital stay (LOS) were compared between patients that had an early PCT determination in ED vs. patients admitted without. Results: Our study cohort consisted of 4056 CAP patients, age 76 [IQ range 64-84] years. We enrolled 1039 patients <65 years old, 2015 aged 65-84 years, and 1002 aged ≥85 years. Overall, the early PCT determination in ED was not associated to a reduced LOS (p=0.630), nor to a reduced mortality rate (p=0.134). However, in patients ≥ 85 years, the PCT determination in ED was associated with lower mortality in those with CURB-65 ≥ 2, and Charlson's score ≥ 2 (p=0.033 and p=0.002, respectively). Conclusions: Although an early PCT assessment in ED was not associated with better outcomes in term of LOS and mortality in patients with CAP, our findings suggest that it might be associated with reduced mortality in patients ≥ 85 years with severe CAP or high comorbidity.

Objectives: Studies on endoscopic treatment of non-anastomotic biliary strictures (NABS) following orthotopic liver transplantation (OLT) are scanty and with a short follow-up. The long-term results of endoscopic treatment with plastic stents of NABS following OLT were analyzed. Methods: Retrospective analysis of consecutive enrolled patients who underwent endoscopic treatment for NABS after OLT between 1997 and 2015. Endoscopic treatment success was defined as stricture resolution, without recurrence. Results: During the study period, 33 patients with NABS underwent endoscopic retrograde cholangiopancreatography (ERCP) in our center. A total of 68 ERCP were performed with a 4.4% of procedure-related adverse events. Mortality related to cholangitis secondary to endoscopic procedures was 12%. After median follow-up of 70.3 months from stents removal, NABS resolution was obtained in 12 out of 24 (50%) patients. Only one case of late NABS recurrence was observed which was successfully retreated endoscopically. According to our data analysis NABS occurring <12 months from OLT showed a worse prognosis (P < 0.04). Conclusions: The follow-up of this study confirms that endoscopic treatment of NABS is unsatisfactory. However, patients who respond to endoscopic treatment maintain the response over time. Prompt treatment of acute cholangitis due to stents occlusion is advised in these patients to avoid high mortality rates.

Background: Safinamide, as a levodopa adjunct, is effective in reducing motor fluctuations in Parkinson’s disease (PD) patients; however, scarce evidence is available regarding its use in older PD patients. Aim: To evaluate the safety and tolerability of safinamide as an adjunct therapy in patients aged ≥ 60 years with advanced PD. Methods: A retrospective study including 203 PD patients admitted to a geriatric day hospital, who were evaluated following an extensive clinical protocol. Safinamide use was categorized as never used, ongoing, and withdrawn. Potential correlations of Safinamide withdrawal were investigated in stepwise backward logistic regression models. Results: A total of 44 out of 203 participants were current or former users of Safinamide. Overall, 14 (32%) patients discontinued due to treatment-emergent adverse events (TEAEs). Withdrawal was not associated with older age. Conclusions: Safinamide as an adjunct therapy in patients aged ≥ 60 years with advanced PD was found to be safe and well-tolerated in older patients. There were no specific demographic or clinical characteristics associated with suspension.

Background: People with Down syndrome (DS) experience premature aging. Whether this accelerated aging also involves early declines in muscle mass, strength and physical performance is presently unclear. The present study investigated the prevalence of sarcopenia parameters in adults with DS. In addition, the relationship between well-established muscle mass indexes and a set of body composition, functional, biological, and clinical parameters was explored. Methods: One hundred-five adults with DS participated in the study. Demographic, clinical, anthropometric, and functional parameters were assessed. Lean body mass (LBM) was estimated using bioelectrical impedance analysis. Bone mineral density (BMD) of the hip and the spine was measured through dual X-ray absorptiometry. For the analysis, participants were categorized into two subgroups (i.e., low and high) for each LBM-related measurement (i.e., crude LBM, LBM to body mass index ratio, and skeletal muscle index) according to their median values. Results: The mean age of participants was 38.4 ± 12.1 years, with 43 men (41%). Muscle mass, handgrip strength, and gait speed were lower than established cutoffs for sarcopenia. All muscle mass indexes were negatively correlated with age. However, only crude LBM and the skeletal muscle index were correlated with a set of anthropometric parameters and BMD. Conclusion: Findings from this exploratory study indicate that adults with DS show muscle mass indexes and physical performance levels similar to or lower than older adults with sarcopenia. The assessment of muscle mass and functional status should therefore be included in the routine evaluation of this population starting at young age.

Background: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD). Research design and methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug–drug interactions. Outcome occurrence was evaluated 180 days after AP initiation. Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27–1.39) for conventional APs. There was no increased mortality risk with single drug–drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00–1.67)). Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.

Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerability to stressors. Having frailty places a person at increased risk of adverse outcomes, including falls, hospitalisation, and mortality. Studies have shown a clear pattern of increased health-care costs and use associated with frailty. All older adults are at risk of developing frailty, although risk levels are substantially higher among those with comorbidities, low socioeconomic position, poor diet, and sedentary lifestyles. Lifestyle and clinical risk factors are potentially modifiable by specific interventions and preventive actions. The concept of frailty is increasingly being used in primary, acute, and specialist care. However, despite efforts over the past three decades, agreement on a standard instrument to identify frailty has not yet been achieved. In this Series paper, we provide an overview of the global impact and burden of frailty, the usefulness of the frailty concept in clinical practice, potential targets for frailty prevention, and directions that need to be explored in the future.

OBJECTIVES: The association of body fat with health status and depression in the oldest old is still debated. The aim of this cross-sectional study is to investigate the association of body fat with health-related quality of life and depression in a sample of nonagenarians. DESIGN: Data are from the Mugello study, a community-based project conducted in Italian older adults aged 90 years. SETTING AND PARTICIPANTS: Total body fat was assessed by body impedance assessment. Participants were divided into 3 groups according to gender-specific tertiles of body fat percentage (BF%). Self-perceived mental and physical health status were assessed by the Mental Component Summary (MCS) and the Physical Component Summary (PCS) subscales derived from the 12-item Short Form Health Survey. Lower scores of MCS and PCS indicated poorer mental health and physical health status, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale, and a score ≥5 was used to identify participants with depression. RESULTS: The mean age of 251 study participants was 92.5 years, and 173 (68.9%) were women. Participants were included in the low (n = 83), medium (n = 83), and high (n = 85) BF% groups. In the whole sample, mean scores at PCS progressively declined with the increasing BF% group (P = .004). This association was stronger in women, although no significant interaction was observed between the gender and BF% group (P = .63). No significant association between BF% and MCS was documented. Medium and high BF% were associated with a significantly higher probability of depression as compared with low BF% [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.04-4.44, and OR 2.15, 95% CI 1.06-4.34, respectively]. This association was stronger in women, although no significant interaction was observed between gender and BF% group (P = .70). CONCLUSIONS AND IMPLICATIONS: High BF% is significantly positively associated with poor health-related quality of life and dep

BACKGROUND: Frailty is common in seniors and is characterized by diminished physiological reserves and increased vulnerability to stressors. Frailty can change the prognosis and treatment approach of several chronic diseases, including COPD. The association between frailty and COPD has never been systematically reviewed.OBJECTIVES: The goal of this study was to conduct a systematic review and meta-analysis assessing the association of COPD with frailty and pre-frailty.METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used when reporting this review. We searched PubMed, Web of Science, and Embase from January 1, 2002, to October 6, 2017. The quality of the studies was evaluated by using the Newcastle Ottawa Scale. Two assessors independently rated each study: scores > 7 were considered a low risk of bias; 5 to 7, a moderate risk of bias; and < 5, a high risk of bias. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity (I-2) and publication bias were assessed.RESULTS: Atotal of 27 studies were selected: 23 cross-sectional, three longitudinal, and one both. The pooled prevalence of pre-frailty in individuals with COPD was 56% (95% CI, 52-60; I-2 = 80.8%); it was 19% (95% CI, 14-24; I-2 = 94.4%) for frailty. Patients with COPD had a two-fold increased odds of frailty (pooled OR, 1.97 [95% CI, 1.53-2.53]; I-2 = 0.0%). Three longitudinal studies, presenting heterogeneous aims and methods, suggested a bidirectional association between COPD and frailty.CONCLUSIONS: Frailty and pre-frailty are common in individuals with COPD. Older subjects with COPD have a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in individuals with COPD and to further investigate any potential negative effects associated with the co-occurrence of these conditions. Longitudinal research that examines temporal associations betw

Multimorbidity is a common and burdensome condition that may affect quality of life, increase medical needs, and make people live more years of life with disability. Negative outcomes related to multimorbidity occur beyond what we would expect from the summed effect of single conditions, as chronic diseases interact with each other, mutually enhancing their negative effects, and eventually leading to new clinical phenotypes. Moreover, multimorbidity mirrors an accelerated global susceptibility and a loss of resilience, which are both hallmarks of aging. Due to the complexity of its assessment and definition, and the lack of clear evidence steering its management, multimorbidity represents one of the main current challenges for clinicians, researchers, and policymakers. The authors of this article recently reflected on these issues during two twin international symposia at the 2016 European Union Geriatric Medicine Society (EUGMS) meeting in Lisbon, Portugal, and the 2016 Gerontological Society of America (GSA) meeting in New Orleans, USA. The present work summarizes the most relevant aspects related to multimorbidity, with the ultimate goal to identify knowledge gaps and suggest future directions to approach this condition.

Background: One of the major threats looming over the growing older population is frailty. It is a distinctive health state characterised by increased vulnerability to internal and external stressors. Although the presence of frailty is well acknowledged, its concept and operationalisation are hampered by the extraordinary phenotypical and biological complexity. Yet, a widely accepted conception is needed to offer tailored policies and approaches. The ADVANTAGE Group aims to analyse the diverse frailty concepts to uncover the essence of frailty as a basis for a shared understanding. Method: A systematic literature review was performed on frailty concepts and definitions from 2010 onwards. Eligible publications were reviewed using concept analysis that led to the extraction of text data for the themes “definition” “attributes” “antecedents” “consequences” and “related concepts”. Qualitative description was used to further analyse the extracted text passages, leading to inductively developed categories on the essence of frailty. Results: 78 publications were included in the review, and 996 relevant text passages were extracted for analysis. Five components constituted a comprehensive definition: vulnerability, genesis, features, characteristics, and adverse outcomes. Each component is described in more detail by a set of defining and explanatory criteria. An underlying functional perspective of health or its impairments is most compatible with the entity of frailty. Discussion: The recent findings facilitate a focus on the relevant building blocks that define frailty. They point to the commonalities of the diverse frailty concepts and definitions. Based on these components, a widely accepted broad definition of frailty comes into range.

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Introduction: Well-conducted observational studies may represent valuable tools for getting insight to disease etiology, detecting the effect of age-related changes, and providing an important perspective on health risk factors and disabilities in an aging population. Nevertheless, this kind of research poses several challenges for researchers. The main aim of this narrative review was to address the potential methodological issues in performing the observational studies in the elderly, the factors that influence their participation, and the possible solutions for overcoming the barriers to research in this population. Methods: Comprehensive search for the papers published in the period from January 1st 1980 until 31st July 2016 in English or Italian was conducted through MEDLINE, Scopus and Web of Science electronic databases. Findings from the included papers were finally summarized. Results: In cohort studies, the following barriers were addressed: sample size calculation, ascertainment of the target population, frequency of data collection, exposure determination, multi factorial loss to follow-up (drop-outs), cognitive impairment, definition of confounders, and ethical aspects. Case-control studies were reported to be prone to the issues like ascertainment of cases and controls, willingness to participate, data accuracy, recall bias, issues related to patients’ multi morbidity, and cognitive impairment. Conclusions: Important factors to consider in research in elderly people include: precise definition of the study population, well conducted recruitment process, engagement with family and home care staff, cognitive impairment assessment and the consequent relevant ethical and legal issues, relief of participant burden in order to minimize withdrawal, and engagement with the media.

Background: Although the definition of multimorbidity as "the simultaneous presence of two or more chronic diseases" is well established, its operationalization is not yet agreed. This study aims to provide a clinically driven comprehensive list of chronic conditions to be included when measuring multimorbidity.Methods: Based on a consensus definition of chronic disease, all four-digit level codes from the International Classification of Diseases, 10th revision (ICD-10) were classified as chronic or not by an international and multidisciplinary team. Chronic ICD-10 codes were subsequently grouped into broader categories according to clinical criteria. Last, we showed proof of concept by applying the classification to older adults from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) using also inpatient data from the Swedish National Patient Register.Results: A disease or condition was considered to be chronic if it had a prolonged duration and either (a) left residual disability or worsening quality of life or (b) required a long period of care, treatment, or rehabilitation. After applying this definition in relation to populations of older adults, 918 chronic ICD-10 codes were identified and grouped into 60 chronic disease categories. In SNAC-K, 88.6% had >= 2 of these 60 disease categories, 73.2% had >= 3, and 55.8% had >= 4.Conclusions: This operational measure of multimorbidity, which can be implemented using either or both clinical and administrative data, may facilitate its monitoring and international comparison. Once validated, it may enable the advancement and evolution of conceptual and theoretical aspects of multimorbidity that will eventually lead to better care.

Summary: This study analyzed data of bone mineral density (BMD) from a large cohort of adults with Down syndrome (DS). BMD was found to decrease with age more rapidly in these subjects than in the general population, exposing adults with DS to an increased risk of osteoporosis and bone fracture. Introduction: Down syndrome (DS) in adulthood presents with a high prevalence of osteoporosis. However, in DS, bone mineral density (BMD) can be underestimated due to short stature. Furthermore, the rate of age-related decline in BMD and its association with gender in DS has been rarely evaluated or compared with the general population. The present study is aimed at assessing the variation of BMD with age and gender in a sample of adults with DS and to compare these data with those of the general population, after adjusting for anthropometric differences. Methods: Adults with DS, aged 18 or older, were assessed dual-energy-X-ray-absorptiometry (DXA) at the femoral neck and at the lumbar spine. They were compared with the general population enrolled in the National Health and Nutrition Examination Survey (NHANES) 2009–2010 dataset. Bone mineral apparent density (BMAD) was calculated for each individual. Results: DXA was evaluated in 234 subjects with DS (mean age 36.93 ± 11.83 years, ranging from 20 to 69 years; 50.4% females). In the lumbar spine both mean BMD (DS 0.880 ± 0.141 vs. NHANES 1.062 ± 0.167, p < 0.001) and BMAD (DS 0.138 ± 0.020 vs. NHANES 0.152 ± 0.020, p < 0.001) were significantly lower in the DS sample than in the NAHNES cohort. The same trend was observed at the femoral neck in both BMD (DS 0.658 ± 0.128 vs. NHANES 0.835 ± 0.137, p < 0.001) and BMAD (DS 0.151 ± 0.030 vs. NHANES 0.159 ± 0.028, p<0.001). Age was associated with lower femoral neck BMAD in both samples; importantly, this association was significantly stronger in the DS sample. In the lumbar spine region, no significant association between BMAD and age could be observed in both samples. Conclusio

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Chronic, low-grade inflammation and declining physical function are hallmarks of the aging process. However, previous attempts to correlate individual inflammatory biomarkers with physical performance in older people have produced mixed results. Given the complexity of the inflammatory response, the simultaneous analysis of an array of inflammatory mediators may provide more insights into the relationship between inflammation and age-related physical function decline. This study was designed to explore the association between a panel of inflammatory markers and physical performance in older adults through a multivariate statistical approach. Methods: Community-dwelling older persons were categorized into "normal walkers" (NWs; n = 27) or "slow walkers" (SWs; n = 11) groups using 0.8 m s -1 as the 4-m gait speed cutoff. A panel of 14 circulating inflammatory biomarkers was assayed by multiplex analysis. Partial least squares-discriminant analysis (PLS-DA) was used to identify patterns of inflammatory mediators associated with gait speed categories. Results: The optimal complexity of the PLS-DA model was found to be five latent variables. The proportion of correct classification was 88.9% for NW subjects (74.1% in cross-validation) and 90.9% for SW individuals (81.8% in cross-validation). Discriminant biomarkers in the model were interleukin 8, myeloperoxidase, and tumor necrosis factor alpha (all higher in the SW group), and P-selectin, interferon gamma, and granulocyte-macrophage colony-stimulating factor (all higher in the NW group). Conclusion: Distinct profiles of circulating inflammatory biomarkers characterize older subjects with different levels of physical performance. The dissection of these patterns may provide novel insights into the role played by inflammation in the disabling cascade and possible new targets for interventions.

Aims: Cognitive dysfunction is a prevalent condition among patients with heart failure, and is independently associated with disability and mortality. Angiotensin-converting enzyme (ACE)-inhibitors might increase cerebral blood flow in subjects with heart failure. Our aim was to assess whether starting treatment with ACE-inhibitors might improve cognition in patients with heart failure. Methods and results: Analyses involved 12 081 subjects, 1220 of whom had a verified diagnosis of heart failure, enrolled in a multi-centre pharmaco-epidemiology survey. None of these participants received ACE-inhibitors before hospitalisation. Among participants with heart failure, cognitive performance improved in 30% of 446 participants who started ACE-inhibitors, but only in 22% of remaining patients (P = 0.001). Among participants without heart failure, cognition improved in 19% of those receiving ACE-inhibitors, and in 18% of untreated patients (P = 0.765). Use of ACE-inhibitors among patients with heart failure was associated with improving cognition (odds ratio = 1.57; 95% Cl 1.18-2.08) also in the multivariable regression modelling, independently of baseline or discharge blood pressure levels. The probability of improving cognitive performance was higher for dosages above the median values, as compared with lower doses (odds ratios = 1.90 and 1.42; P for trend = 0.001), and increased with duration of treatment (odds ratios for the lower, middle, and upper tertiles = 1.25, 1.34, and 1.59; P for trend = 0.007). Conclusion: Treatment with ACE-inhibitors might selectively improve cognitive performance in patients with heart failure. However, up-titration of these agents might be required to yield the greatest benefit.

PURPOSE: Cognitive impairment is a common, potentially reversible condition among older patients with heart failure. Because cerebral metabolic abnormalities have been associated with reduced survival in younger patients with advanced heart failure, we assessed the effect of cognitive impairment on the survival of older patients with heart failure. METHODS: The association between cognitive dysfunction and in-hospital mortality was assessed in 1113 patients (mean [± SD] age, 78 ± 9 years) who had been admitted for heart failure to 81 hospitals throughout Italy. One-year mortality was assessed in 968 patients with heart failure (age, 76 ± 10 years) participating in the same study. Cognitive impairment was defined as a Hodkinson Abbreviated Mental Test score <7. RESULTS: In-hospital death occurred in 65 (18%) of the 357 participants with cognitive impairment and in 26 (3%) of the 756 patients with normal cognition (P <0.0001). Out-of-hospital mortality was 27% (51/191) among patients with cognitive impairment and 15% (115/777) among other participants (P <0.0001). In multivariate Cox regression models, decreasing levels of cognitive functioning were associated with increasing in-hospital mortality; cognitive impairment was associated with an almost fivefold increase in mortality (relative risk = 4.9; 95% confidence interval: 2.9 to 8.3) after adjusting for several potential confounders. CONCLUSION: Cognitive impairment is an independent prognostic marker in older patients with heart failure. Assessment of cognitive functioning, even by simple screening tests, should be part of the routine assessment of elderly patients with heart failure. © 2003 by Excerpta Medica Inc.