An Innovative AAL System Based on IoT Technologies for Patients with Sarcopenia.

Sarcopenia is a highly prevalent, age-related muscle disorder associated with adverse outcomes. It is very important from a medical point of view to periodically monitor patients at risk of developing sarcopenia in order to early detect its onset or progression through objective and specific indicators. Today, the emerging Internet of Things (IoT)-enabling technologies allow us to create innovative, wearable, and non-invasive systems that can offer useful clinical support in this area. This work is focused on the use of combined hardware and software technologies, enabling the IoT, in order to monitor people suffering from sarcopenia by offering a high value-added service in the field of the Ambient Assisted Living (AAL). In addition to the description of the proposed system architecture, a validation of the entire system is also included, from both a performance and a functional point of view. Test beds have been carried out by using the independent replications method, and all measurements related to the identified sarcopenia parameters are characterized by a 95% confidence interval with a 5% maximum relative error. The implementation of these technologies as a supporting clinical tool used in a specific setting could significantly impact the life and independence of the sarcopenic frail elderly population.

Insomnia and Information and Communication Technologies (ICT) in Elderly People: A Systematic Review.

Background: Insomnia seems to be related to disability, risk of injury, metabolic syndrome, risk for cardiovascular diseases, cognitive impairment, depression and impaired quality of life. Objectives: The goals in this paper was (1) to keep track of technological concepts and approaches to improve insomnia in elderly people, and (2) to define the effect that information and communication technologies (ICT) is having on patients' care. Design: A systematic review was conducted from existing literature. Our selection criteria included: (1) age ≥ 60 years; (2) diagnosis of insomnia with the International Classification of Sleep Disorders (ICSD-II), (3) CBTi (cognitive behavioural therapy insomnia), (4) use of technological tools, and (5) associations between insomnia-related variables and indices of disability, quality of life, and global clinical assessments. Data analysis: 11 articles were included. An inductive content analysis was used for data extraction. Results: Our review revealed any technological systems that could purportedly rehabilitate elderly patients with insomnia. Three categories of research were identified from the review: (1) Internet Deliver-CBTi, (2) virtual coaches, and (3) sleep technologies. Conclusions: The potential for ICT to support insomnia care at home can improve the quality of life for families and reduce health care costs and premature institutional care.

Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease.

BACKGROUND: Serotoninergic pathways underlying delusion symptoms in Alzheimer's disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. METHODS: We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer's Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. RESULTS: Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121-0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522-0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195-4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. CONCLUSIONS: More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.

Multidimensional Prognostic Index and pro-adrenomedullin plasma levels as mortality risk predictors in older patients hospitalized with community-acquired pneumonia: a prospective study.

BACKGROUND: To evaluate the prognostic accuracy of proadrenomedullin (proADM) in comparison with and in addition to the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a comprehensive geriatric assessment (CGA) to predict one-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP). METHODS: All patients aged 65 years and older, consecutively admitted to an acute geriatric ward with a diagnosis of CAP from February to July 2012. At admission and at discharge they were submitted to a standard CGA in order to calculate MPI. Moreover, plasma samples were taken at baseline and after one, three and five days of hospitalization for the analysis of pro-ADM. RESULTS: Fifty patients (mean age 86.2±7.5 years), with 31 at high risk of mortality (MPI-3) were enrolled. ProADM and MPI, both at admission and at discharge, were significant predictor of mortality. As expected, MPI at admission showed lower predictive accuracy than MPI at discharge (survival C-statistic 0.667 vs. 0.851). The addition of proADM to the MPI at admission significantly increased accuracy in predicting one-month mortality (C-statistics from 0.667 to 0.731, P=0.018 at baseline; from 0.667 to 0.733, P=0.008 at 1 day; from 0.633 to 0.724; P=0.019 at 3 days; from 0.667 to 0.828; P=0.003 at 5 days). Conversely, adding pro-ADM to the MPI at discharge did not significantly improve the model's prognostic accuracy. CONCLUSIONS: ProADM may significantly improve the prognostic accuracy of the MPI at admission in hospitalized elderly patients with CAP.

Executive Dysfunction Detected with the Frontal Assessment Battery in Alzheimer's Disease Versus Vascular Dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) lead to progressive decline in executive function. We estimated the prevalence of executive dysfunction in AD and VaD patients, investigating cognitive, functional, and clinical correlates and also using a multidimensional approach based on a standardized comprehensive geriatric assessment (CGA). We included 215 patients (115 AD patients and 100 VaD patients) consecutively evaluated with a complete cognitive and affective assessment, a CGA, and the Frontal Assessment Battery (FAB) with six subtests investigating conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. The prevalence of dysexecutive syndrome screened with a FAB score <12 points was high in both AD (97 patients) and VaD (77 patients) (84.3% versus 77.0%, p = 0.171). AD patients were significantly younger, with higher grade of cognitive impairment and less severe comorbidity and polypharmacy than VaD patients. AD patients showed a significantly higher impairment in FAB total score and five FAB subtests (conceptualization, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy) than VaD patients. These findings were largely confirmed in a sub-analysis conducted subdividing the sample in mild and moderate-to-severe demented patients and suggesting that in moderate-to-severe AD there was higher impairment in FAB total score and four FAB subtests (conceptualization, sensitivity to interference, inhibitory control, and environmental autonomy). Executive dysfunction could be greater in AD patients with moderate-to-severe dementia compared to VaD patients, although our groups were also not matched for age, comorbidity or polypharmacy, which could also exert an effect.

Combined use of the multidimensional prognostic index (MPI) and procalcitonin serum levels in predicting 1-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP): a prospective study.

BACKGROUND: Several scores and biomarkers, i.e., procalcitonin (PCT), were proposed to stratify the mortality risk in community-acquired pneumonia (CAP). AIM: Evaluating prognostic accuracy of PCT and Multidimensional Prognostic Index (MPI) for 1-month mortality risk in older patients with CAP. METHODS: At hospital admission and at discharge, patients were evaluated by a Comprehensive Geriatric Assessment to calculate MPI. Serum PCT was measured at admission and 1, 3, and 5 days after hospital admission. RESULTS: 49 patients were enrolled. The overall 1-month mortality was 44.5 for 100-persons year. Mortality rates were higher with the increasing of MPI. In survived patients, MPI at discharge showed higher predictive accuracy than MPI at admission. Adding PCT levels to admission MPI prognostic accuracy for 1-month mortality significantly increased. CONCLUSION: In older patients with CAP, MPI significantly predicted 1 month mortality. PCT levels significantly improved the accuracy of MPI at admission in predicting 1-month mortality.

Analysis of MTNR1B gene polymorphisms in relationship with IRS2 gene variants, epicardial fat thickness, glucose homeostasis and cognitive performance in the elderly.

ABSTARCT Genome-wide association studies pinpointed common variants in or near the MTNR1B gene encoding MT2 melatonin receptor to be strongly associated with fasting glucose levels. IRS2 gene polymorphisms impact insulin resistance and epicardial fat (EF) thickness, which in turn is correlated with visceral adiposity, cognitive ability and risk for metabolic plus cardiovascular disease. We aimed to discover the interactions between MTNR1B and IRS2 gene polymorphisms, insulin sensitivity, EF thickness and cognitive performance in the elderly. In 60 subjects aged 60 years and older, we evaluated five single nucleotide polymorphisms (SNPs) within the MTNR1B locus (rs10830962, rs4753426, rs12804291, rs10830963, rs3781638), the Gly1057Asp variant of IRS2 gene (rs1805097), biochemical parameters, cognitive performance by the Mini Mental State Examination (MMSE) and EF thickness by transthoracic echocardiography. We found that MTNR1B and IRS2 gene variants impacted EF thickness, lipid profile and glucose homeostasis. IRS2 but not MTNR1B variants impacted MMSE scores. In conclusion, MTNR1B SNPs interact with IRS2 gene variant, correlate with the amount of epicardial adipose tissue and impact glucose homeostasis and lipid profile influencing cardiometabolic risk.

Klotho Gene and Selective Serotonin Reuptake Inhibitors: Response to Treatment in Late-Life Major Depressive Disorder.

Klotho protein, encoded by the Klotho gene (KL) at locus 13q12, is an antiaging hormone-like protein playing a pivotal role in cell metabolism homeostasis and associated to longevity and age-related diseases. In particular, altered cell metabolism in central nervous system may influence the behavior of serotoninergic neurons. The role of KL in the response to treatment with selective serotonin reuptake inhibitors (SSRIs) in late-life depressive syndromes and late-life major depressive disorder (MDD) is unclear. We genotyped three single-nucleotide polymorphisms (SNPs) of KL in 329 older patients with diagnosis of late-life MDD, treated with SSRIs and evaluated with the Hamilton Rating Scale for Depression 21-items (HRSD-21) at baseline and after 6 months. A reduction ≥50 and <10 % in HDRS-21 score was considered as response or nonresponse to therapy, respectively, and the values of reduction between 10 and 49 % as poor responders. After 6 months of SSRI treatment, 176 patients responded, 54 patients did not respond and 99 patients showed a poor response. Ordinal logistic models showed a significant association between mutation of SNP rs1207568 and responders and, similarly, for each unitary risk allele increase overlapping results were found. Conversely, a significantly higher frequency of the minor genotype of SNP rs9536314 was found in nonresponders. Considering the pre-post differences of HRSD-21 scores as a continue variable, we confirmed a significant improvement of depressive symptoms after treatment in patients carrying at least one minor allele at rs1207568 and a worse response in patients homozygous for the minor allele at rs9536314. Our results were the first that suggested a possible role of KL in the complex pathway of SSRI response in late-life MDD.

Caregiver burden characterization in patients with Alzheimer's disease or vascular dementia.

OBJECTIVE: To characterize the differences of caregiver burden in patients with Alzheimer's disease (AD) and vascular dementia (VaD) in order to improve the care counselling and management plan. METHODS: We included 506 patients consecutively attending the Alzheimer's Evaluation Unit of a Geriatric Unit, evaluated with Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression, and Neuropsychiatric Inventory. To all caregivers were administered the Caregiver Burden Inventory (CBI), a 24-item multidimensional questionnaire in which 5 subscales explore 5 dimensions of caregiver burden: (1) CBI-Objective; (2) CBI-Developmental; (3) CBI-Physical; (4) CBI-Social; and (5) CBI-Emotional. RESULTS: The present study included, respectively, 253 AD patients and 253 VaD patients. AD patients at baseline showed a significantly higher instruction level (p < .0001), higher grade of cognitive impairment (MMSE, p < .0001), and increased severity stage of dementia (CDR, p < .0001) than VaD patients. AD caregivers, mainly females (p = 0.010), devoted significantly more length of time care (in months, p = 0.010) and time of daily care (in hours, p = 0.011) and showed a significantly higher burden level in CBI-Objective (p = 0.047), CBI-Physical (p < .0001), CBI-Social (p = 0.003), CBI-Emotional (p < .0001), and CBI-total score (p < .0001), than VaD caregivers. In both caregiver groups, a higher presence of spouses and sons (p < .0001) compared to other relatives was observed. AD caregiver burden showed a significant association with sex of caregivers and length of time care in months. CONCLUSIONS: AD caregivers showed a higher burden level than VaD caregivers, and this appeared to be associated with sex and length of time care.

A pilot randomized controlled trial evaluating an integrated treatment of rivastigmine transdermal patch and cognitive stimulation in patients with Alzheimer's disease.

OBJECTIVE: To evaluate in a pilot single-blind randomized controlled clinical trial the efficacy of an integrated treatment with rivastigmine transdermal patch (RTP) and cognitive stimulation (CS) in Alzheimer's disease (AD) patients at 6-month follow-up. METHODS: We enrolled 90 patients with an age ≥65 years admitted to the outpatient Alzheimer's Evaluation Unit with diagnosis of AD. Patients were randomized to enter in the Group-1 (RTP + CS) or in the Group-2 (RTP). All patients at baseline and after 6 months were evaluated with the following tools: Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression (HAM-D), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-Distress (NPI-D), and a standardized Comprehensive Geriatric Assessment, including also activities of daily living (ADL), instrumental activities of daily living (IADL), and the Mini Nutritional Assessment (MNA). Mortality risk was assessed using the Multidimensional Prognostic Index (MPI). RESULTS: At baseline no significant difference was shown between the two groups. After 6 months of follow-up, there were significant differences between Group-1 and Group-2 in: MMSE: +6.39% vs. +2.69%, CDR: +6.92% vs. +1.54%, HDRS-D = -60.7% vs. -45.8%, GDS: -60.9% vs. -7.3%, NPI: -55.2% vs. -32.7%%, NPI-D: -55.1% vs. -18.6%, ADL: +13.88% vs. +5.95%, IADL: +67.59% vs. +18.28%, MNA: +12.02% vs. +5.91%, and MPI: -29.03% vs. -12.90%. CONCLUSION: The integrated treatment of RTP with CS in AD patients for 6 months improved significantly cognition, depressive and neuropsychiatric symptoms, functional status, and mortality risk in comparison with a group of AD patients receiving only RTP.

An association study between epicardial fat thickness and cognitive impairment in the elderly.

The amount of fat surrounding the heart, called epicardial adipose tissue (EAT), is a marker of cardiometabolic risk and correlates with the quantity of visceral adipose tissue (VAT). The amount of VAT is associated with an increased risk of cardiovascular and cerebrovascular disease and with cognitive impairment. We aimed to evaluate the association between EAT thickness as a measure of VAT and cognitive function. In 71 elderly subjects (mean age 72.7 ± 7.1 yr) we measured EAT thickness through transthoracic echocardiography, assessed the metabolic profile through evaluation of biochemical parameters, and estimated the cognitive function via the Mini Mental State Examination (MMSE). We found that greater EAT thickness was associated with lower cognitive performance evaluated by MMSE (P < 0.01) independently of the presence or absence of metabolic syndrome or obesity. Lower MMSE results were also associated with the presence of metabolic syndrome (P < 0.01), elevated HOMA index (P < 0.01), and high BMI values (P < 0.01). The results of mediation analysis confirmed that the total effect of metabolic syndrome, HOMA, and BMI on MMSE is mainly explained by an indirect effect through EAT thickness. In conclusion, increased EAT thickness assessed by transthoracic echocardiography is associated with deficient results of psychometric tests assessing cognitive performance and may consistently foresee impairment of cognition in the elderly.

Frailty, disability and physical exercise in the aging process and in chronic kidney disease.

Frailty in the elderly is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. It is usually associated to adverse health outcomes and to one-year mortality risk. Physical exercise has found to be effective in preventing frailty and disability in this population. Chronic kidney disease (CKD) is also a clinical condition where protein energy-wasting, sarcopenia and dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly and CKD patients are both affected by an impaired physical performance that may be reversed by physical exercise with an improvement of the survival rate. These similarities suggest that frailty may be a common pathway of aging and CKD that may induce disability and that can be prevented by a multidimensional approach in which physical exercise plays an important role.

Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients.

A combination of several metabolic and hormonal adaptations has been proposed to control aging. Little is known regarding the effects of multiple deregulations of these metabolic and hormonal systems in modulating frailty and mortality in hospitalized elderly patients. We measured 17 biological serum parameters from different metabolic/hormonal pathways in 594 hospitalized elderly patients followed up to 1 year who were stratified into three groups according to their multidimensional impairment, evaluated by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI). The mortality incidence rates were 7% at 1 month and 21% at 1 year. Our data show that frailty and mortality rate were positively associated with chronic inflammation and with a down-regulation of multiple endocrine factors. Of the 17 biomarkers examined, blood levels of IGF-1, triiodothyronine, C-reactive protein, erythrocyte sedimentation rate, white blood cell and lymphocyte counts, iron, albumin, total cholesterol, and LDL-c were significantly associated with both MPI severity grade and mortality. In multivariate Cox proportional hazard model, the following biomarkers most strongly predicted the risk of mortality (adjusted hazard ratio (HR) per 1 quintile increment in predictor distribution): IGF-1 HR = 0.71 (95% CI: 0.63-0.80), CRP HR = 1.48 (95% CI: 1.32-1.65), hemoglobin HR = 0.82 (95% CI: 0.73-0.92), and glucose HR = 1.17 (95% CI: 1.04-1.30). Multidimensional impairment assessed by MPI is associated with a distinctive metabolic 'signature'. The concomitant elevation of markers of inflammation, associated with a simultaneous reduction in multiple metabolic and hormonal factors, predicts mortality in hospitalized elderly patients.

Forkhead-box-O1 locus y marcadores metabólicos en los ancianos: estudio de asociación / Forkhead-box-O1 locus and metabolic markers in the elderly: An association study

Introducción. Las mutaciones del gen forkhead-box-O1 (FoxO1) en el locus 13q14.1 provocan alteraciones en los parámetros bioquímicos conduciendo al envejecimiento prematuro. La proteína FoxO1 participa en la regulación de procesos bioquímicos, que influyen en la regulación del perfil lipídico y glucémico. Estos parámetros son un factor de riesgo de mortalidad en la población anciana. El objeto del estudio fue investigar la relación entre el locus FoxO1 y los marcadores metabólico-nutricionales. Material y métodos. Se investigaron los polimorfismos de nucleótido único (SNP, del inglés single-nucleotide polymorphisms) rs2721069, rs4943794 y rs7981045 en 594 ancianos hospitalizados (65-99 años) en una sección geriátrica, probando la asociación con los marcadores biológicos mediante el análisis de covarianza (ANCOVA) y del modelo estadístico Genotype Score. Resultados. El análisis de ANCOVA bajo distintos modelos genéticos reveló una asociación significativa. Asumiendo un modelo genético dominante se observó una asociación significativa con los niveles de la glucosa para rs2721069 (p=0,034) y rs4943794 (p=0,012). Para rs4943794 se observó también una asociación significativa si considerado libre de modelos genéticos (p=0,039) confirmada en el modelo aditivo (p=0,012). El modelo estadístico Genotype Score confirmó una asociación significativa entre FoxO1 SNP y la glucosa, teniendo en cuenta los SNP rs2721069 y rs4943794 en conjunto (p=0,048; Beta=3,198). Conclusiones. El envejecimiento es un proceso complejo, resultante de la interacción entre varios factores, como los ambientales y los genéticos. Nuestros hallazgos sugieren que el locus FoxO1 puede influir en los niveles séricos de glucemia en pacientes hospitalizados mayores, siendo entonces uno de los factores genéticos que contribuyen a un envejecimiento saludable(AU)

Introduction. Mutations of forkhead-box-O1 (FOXO1) gene at locus 13q14.1 cause changes in biochemical parameters leading to premature aging. Protein FoxO1 participates in the regulation of biochemical pathways, including those influencing the regulation of lipid profile and glucose metabolism. These parameters are a risk factor for all-cause mortality in the elderly population. The aim of this study was to investigate the relationship between FOXO1 locus and metabolic-nutritional markers. Material and methods. Single-nucleotide polymorphisms (SNP) rs2721069, rs4943794 and rs7981045 were determined in 594 hospitalized elderly (65-99 years), patients consecutively admitted to a geriatric ward, and tested the association of FOXO1 variants with biological markers by the analyses of co-variance (ANCOVA) and by Genotype Score Model statistic. Results. The ANCOVA analysis, under different genetic models, revealed significant associations. In particular, assuming a dominant genetic model, a significant association with serum levels of fasting glucose was observed for rs2721069 (P=.034) and rs4943794 (P=.012). For rs4943794 a significant association assuming a free genetic model (P=.039) and an additive one (P=.012) was also observed. No significant relationship was observed between rs7981045 and the analyzed markers. The Genotype Score Model analysis confirmed a significant association between FOXO1 SNP and fasting glucose, taking the SNP rs2721069 and rs4943794 together (P=.048; Beta=3.198). Conclusions. Aging is a complex process, resulting from the interaction between several factors, including environmental and genetic ones. Our findings suggest that FOXO1 locus may influence blood glucose levels in hospitalized older patients, thus being one of the genetic factors contributing to healthy aging(AU)

[Forkhead-box-O1 locus and metabolic markers in the elderly: an association study]. / Forkhead-box-O1 locus y marcadores metabólicos en los ancianos: estudio de asociación.

INTRODUCTION: Mutations of forkhead-box-O1 (FOXO1) gene at locus 13q14.1 cause changes in biochemical parameters leading to premature aging. Protein FoxO1 participates in the regulation of biochemical pathways, including those influencing the regulation of lipid profile and glucose metabolism. These parameters are a risk factor for all-cause mortality in the elderly population. The aim of this study was to investigate the relationship between FOXO1 locus and metabolic-nutritional markers. MATERIAL AND METHODS: Single-nucleotide polymorphisms (SNP) rs2721069, rs4943794 and rs7981045 were determined in 594 hospitalized elderly (65-99 years), patients consecutively admitted to a geriatric ward, and tested the association of FOXO1 variants with biological markers by the analyses of co-variance (ANCOVA) and by Genotype Score Model statistic. RESULTS: The ANCOVA analysis, under different genetic models, revealed significant associations. In particular, assuming a dominant genetic model, a significant association with serum levels of fasting glucose was observed for rs2721069 (P=.034) and rs4943794 (P=.012). For rs4943794 a significant association assuming a free genetic model (P=.039) and an additive one (P=.012) was also observed. No significant relationship was observed between rs7981045 and the analyzed markers. The Genotype Score Model analysis confirmed a significant association between FOXO1 SNP and fasting glucose, taking the SNP rs2721069 and rs4943794 together (P=.048; ß=3.198). CONCLUSIONS: Aging is a complex process, resulting from the interaction between several factors, including environmental and genetic ones. Our findings suggest that FOXO1 locus may influence blood glucose levels in hospitalized older patients, thus being one of the genetic factors contributing to healthy aging.

The nephro-geriatric unit in a lean-oriented in-hospital model of care.

Nephrologists worldwide are gradually coping with elderly patients. This is because of the burden of chronic disease in the aging population and specifically chronic kidney disease (CKD). CKD in the elderly rarely occurs in isolation from other chronic conditions and can often be a marker of these conditions themselves. Geriatricians usually take care of chronic conditions and are trained to perform comprehensive geriatric assessment, a tool to estimate frailty, that is the risk of adverse outcome, disability, and death in the clinical setting of elderly inpatients. Unfortunately, they are not used to a CHD invasive and non-invasive approach and so there is no doubt about the need for a co-managed care model for these patients. However, where and how this model must be realized is still questionable. New hospital care models are patient-centered and encompass the concepts of departments to embrace the differentiated levels of care approach. According to this model the hospital is subdivided into three different standards of care: 1-high; 2 -intermediate; 3- low and this organization avoids inpatients being transferred frequently to different units, receiving specific care easily obtained by moving and changing the medical staff in charge of the patient. The lean care approach integrates the principles of the Toyota Producing System (TPS), a leading system of the industrial world, into intensity-based hospital care, thereby maximizing quality processes and promoting co-managed care as in the nephro-geriatric clinical setting.

Addition of the multidimensional prognostic index to the estimated glomerular filtration rate improves prediction of long-term all-cause mortality in older patients with chronic kidney disease.

Current prognostic scores of chronic kidney disease (CKD) are not accurate in older patients. The aim of this study was to evaluate the prognostic accuracy of the Multidimensional Prognostic Index (MPI) in comparison with and in addition to the estimated glomerular filtration rate (eGFR) to predict long-term all-cause mortality in hospitalized older patients with CKD. In a prospective cohort study with a mean follow-up of 2 years, we calculated eGFR according to the Modification of Diet in Renal Disease study and collected information on functional, cognitive, nutritional, co-morbidities, drug use, and co-habitation status to calculate the MPI on 1,198 patients aged ≥65 years with a diagnosis of CKD from an hospital-based sample. The all-cause mortality incidence rate for 100 person-years was 18.3 (men 22.7 vs. women 15.3, p<0.0001). Adding the MPI to the eGFR model significantly improved all-cause mortality prediction accuracy: The C-index increased from 0.579 to 0.648 (p<0.0001), with correct reclassification of 25.9% of patients (Net Reclassification Improvement [NRI], 0.259, p<0.0001; Integrated Discrimination Improvement [IDI], 3.8%, p<0.0001). The correct reclassification was higher in patients who did not die (259/741 patients, reclassification rate=34.9%) than in patients who died (62/457 patients, reclassification rate=13.6%). Conversely, adding the eGFR to the MPI model seems to improve prediction accuracy less consistently. In fact, the C-index increased, but not significantly (from 0.639 to 0.648, p=0.444), with correct reclassification of 5.8% of patients (NRI, 0.058, p=0.012; IDI, 0.009, p=0.001), suggesting a small, although significant improvement. Adding MPI information to the eGFR markedly improved the prediction of 2-year all-cause mortality in older patients with CKD. A multidimensional evaluation for all-cause mortality risk prediction should be considered in older patients with CKD.

Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis.

Klotho (KL) gene has been involved in severe alterations of physiological biochemical parameters leading to premature aging-like phenotypes and strikingly shortening lifespan. KL participates to the regulation of a number of intracellular biochemical pathways, including lipid profile and glucose metabolism. Aim of this study was to investigate the possible association between KL locus and biological parameters commonly accepted as indicators of the clinical status in hospitalized older patients. We genotyped the single-nucleotide polymorphisms (SNPs) rs9536314, rs1207568, and rs564481 at the KL locus in 594 hospitalized older patients (65-99 years), consecutively attending a geriatric ward, and tested the association of these KL variants with biological quantitative traits using analyses of covariance and genetic risk score models. Significant associations of rs9536314 with serum levels of hemoglobin, albumin, and high-density lipoprotein cholesterol (HDL-C) as well as significant associations of rs564481 with serum levels of hemoglobin, fasting insulin, and fasting glucose were observed. Gender-segregated analyses confirmed these associations, and suggested that the associations of KL genotypes with HDL-C, fasting glucose and fasting insulin levels may be driven by the female gender, while the association with serum levels of hemoglobin may be driven by the male gender. The association of KL genotypes with creatinine levels was found only in females, while the association with insulin-like growth factor-1 (IGF-1) and lymphocytes count (LC) was found only in males. The genetic risk score (GRS) models further confirmed significant associations among KL SNPs and hemoglobin, total cholesterol, and HDL-C. Gender-segregated analyses with the GRS-tagged approach confirmed the associations with HDL-C, fasting glucose, and fasting insulin levels in females, and with hemoglobin and LC in males. Our findings suggested that KL locus may influence quantitative traits such as serum levels of lipid, fasting glucose, albumin and hemoglobin in hospitalized older patients, with some gender differences suggested for creatinine, IGF-1 levels, and LC, thus being one of the genetic factors possibly contributing to age-related diseases and longevity.

Effect of obesity, serum lipoproteins, and apolipoprotein E genotypes on mortality in hospitalized elderly patients.

BACKGROUND: The aim of this study was to investigate the relationship among apolipoprotein E (APOE) polymorphism, body mass index (BMI), and dyslipidemia and how these factors modify overall mortality in a cohort of hospitalized elderly patients. METHODS: Plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), BMI, and APOE genotype were evaluated in 1,012 hospitalized elderly patients, who were stratified into three groups according to their baseline BMI and APOE allele status. Multivariate logistic regression analysis was used to assess whether APOE genotype, BMI, and dyslipidemia are associated with mortality, adjusting for potential confounders. Interaction analysis was also performed. RESULTS: Obese patients have significantly higher levels of TC and LDL-C compared to normal-weight and overweight subjects, for both sexes. APOE ε4 carriers have significantly higher levels of TC and LDL-C compared with ε2 and ε3 carrier both in males and females. Interaction analysis showed that women with TC < 180 mg/dL, LDL-C < 100 mg/dL, normal weight, and ε3 carrier (odds ratio [OR] = 3.42, 95% confidence interval [CI] 1.36-8.60) and men with LDL-C < 100 mg/dL, HDL-C < 40 mg/dL, and ε3 carrier (OR = 1.97, 95% CI 1.04-3.74) were at highest risk of mortality. CONCLUSIONS: In elderly hospitalized patients, obesity and APOE genotype influence the lipid profile and mortality risk. A significant interaction among BMI, dyslipidemia, and APOE genotype was observed that could identify elderly patients with different risks of mortality.

Apolipoprotein E-related all-cause mortality in hospitalized elderly patients.

The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 +/- 7.1 years; range, 65-100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE epsilon2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37-0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the epsilon2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36-0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.