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Padova, Italy

Fontana L.,University of Salerno | Fontana L.,Washington University in St. Louis | Addante F.,Gerontology Geriatric Research Laboratory | Copetti M.,Unit of Biostatistics | And 7 more authors.
Aging Cell | Year: 2013

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. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

Pilotto A.,Geriatrics Unit | Pilotto A.,Institute of Care and Scientific Research Casa Sollievo della Sofferenza | Rengo F.,University of Naples Federico II | Rengo F.,Institute of Care and Scientific Research | And 5 more authors.
PLoS ONE | Year: 2012

Background: Frailty is a dynamic age-related condition of increased vulnerability characterized by declines across multiple physiologic systems and associated with an increased risk of death. We compared the predictive accuracy for one-month and one-year all-cause mortality of four frailty instruments in a large population of hospitalized older patients in a prospective multicentre cohort study. Methods and Findings: On 2033 hospitalized patients aged ≥65 years from twenty Italian geriatric units, we calculated the frailty indexes derived from the Study of Osteoporotic Fractures (FI-SOF), based on the cumulative deficits model (FI-CD), based on a comprehensive geriatric assessment (FI-CGA), and the Multidimensional Prognostic Index (MPI). The overall mortality rates were 8.6% after one-month and 24.9% after one-year follow-up. All frailty instruments were significantly associated with one-month and one-year all-cause mortality. The areas under the receiver operating characteristic (ROC) curves estimated from age- and sex-adjusted logistic regression models, accounting for clustering due to centre effect, showed that the MPI had a significant higher discriminatory accuracy than FI-SOF, FI-CD, and FI-CGA after one month (areas under the ROC curves: FI-SOF = 0.685 vs. FI-CD = 0.738 vs. FI-CGA = 0.724 vs. MPI = 0.765, p<0.0001) and one year of follow-up (areas under the ROC curves: FI-SOF = 0.694 vs. FI-CD = 0.729 vs. FI-CGA = 0.727 vs. MPI = 0.750, p<0.0001). The MPI showed a significant higher discriminatory power for predicting one-year mortality also in hospitalized older patients without functional limitations, without cognitive impairment, malnourished, with increased comorbidity, and with a high number of drugs. Conclusions: All frailty instruments were significantly associated with short- and long-term all-cause mortality, but MPI demonstrated a significant higher predictive power than other frailty instruments in hospitalized older patients. © 2012 Pilotto et al.

Gallucci M.,Cognitive Impairment Center | Battistella G.,Service of Statistics and Epidemiology | Bergamelli C.,Cognitive Impairment Center | Spagnolo P.,Cognitive Impairment Center | And 5 more authors.
Journal of Alzheimer's Disease | Year: 2014

Background: The Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment has been developed to predict mortality in hospitalized elderly patients. The Treviso Dementia (TREDEM) Study is an observational prospective cohort study of 1,364 outpatients evaluated at the Cognitive Impairment Center in Treviso, Italy from 2000 to January 2010.Objective: To use the MPI in the TREDEM outpatient setting to assess the correlation of MPI with mortality and hospitalizations for acute cases that occurred after the date of assessment.Methods: MPI was consecutively applied to the last 340 of 1,364 outpatients who were evaluated at the Center from 2008 to January 2010, after the first publication of MPI index in 2008. Participants' mortality was verified by linking the cohort with Registries of Municipalities, National Register of Revenue Authorities, and Nominal Register of Causes of Death. Data about hospitalizations for acute cases that occurred within 12 months after the date of assessment were obtained from all Italian hospitals. A Cox regression method was used to investigate the effect of MPI upon mortality and hospitalizations, also considering confounder factors such as age and gender.Results: 114 men and 226 women, aged 52.1-99 years (mean age 80.4 years), were studied and had an MPI mean of 0.41. On 15 February 2013, 100 were deceased, and average hospitalizations for acute cases were 0.3, days 3.8. For MPI scores between 0 and 1, the increase in the probability of death was more than nine times (odds: 9.53 p = 0.0002) and of hospitalization was more than six times (odds: 6.50, p = 0.0079).Conclusion: MPI discloses the risk of death and of hospitalizations for acute cases in outpatients affected by cognitive impairment. © 2014-IOS Press and the authors. All rights reserved.

Seripa D.,Gerontology Geriatrics Research Laboratory | D'Onofrio G.,Gerontology Geriatrics Research Laboratory | Panza F.,Gerontology Geriatrics Research Laboratory | Cascavilla L.,Gerontology Geriatrics Research Laboratory | And 2 more authors.
Rejuvenation Research | Year: 2011

The genetic origin of the three common variants of the human apolipoprotein E (apoE) protein, known as E2, E3 and E4, was understood in 1981, and since the mid 1980s these are probably the most-studied protein variants in human races. They have been related to a number of age-related diseases, including Alzheimer disease, as well as to healthy aging and longevity. The gene variants underlying these protein isoforms, known as ε2, ε3, and ε4, are allelic forms of the APOE gene, resulting from different haplotypes at the APOE locus (19q13.31). In particular, they result from three of the four haplotypes expected by the combinations of the alleles of the two single-nucleotide polymorphisms rs429358 and rs7412. The fourth missing haplotype, known as ε3r, has been identified in only two Caucasian families from Italy and in one Yoruba family from Nigeria worldwide. Thus, this fourth APOE gene variant is rare, and it encodes a protein isoform, identified as E3r, showing identical physical characteristics to E3, that conversely, is the most common form of apoE in humans. In this review article, we report the identification of the haplotype ε3r in a third Caucasian family from Italy, and then attempt to re-examine the current knowledge regarding the APOE polymorphism, taking into account this fourth haplotype. We also focus on the commonly accepted hypothesis for the evolution of the common APOE gene variants, in which we include the ε3r haplotype, previously not considered. © 2011 Mary Ann Liebert, Inc.

Volpato S.,University of Ferrara | Bazzano S.,Geriatrics Unit | Bazzano S.,Geriatric Gerontology Research Unit | Fontana A.,Scientific Institute for Research and Care | And 3 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2015

Background: The Multidimensional Prognostic Index (MPI) is a validated predictive tool for long-term mortality based on information collected in a standardized Comprehensive Geriatric Assessment. We investigated whether the MPI is an effective predictor of intrahospital mortality and length of hospital stay after admission to acute geriatric wards. Methods: Prospective study of 1,178 older patients (702 women and 476 men, 85.0 ± 6.8 years) admitted to 20 geriatrics units. Within 48 hours from admission, the MPI, according to an earlier validated algorithm, was calculated. Subjects were divided into three groups of MPI score, low-risk (MPI-1 value. 0.33), moderate-risk (MPI-2 value, and severe-risk of mortality (MPI-3 value. 0.67), on the basis of earlier established cut-offs. Associations with in-hospital mortality and length of stay were examined using multivariable Cox regression models and adjusted Poisson linear mixed-effects models, respectively. Results: At admission, 23.6% subjects had a MPI-1 score, 33.8% had a MPI-2 score, and 42.6% had a MPI-3 score. Subjects with higher MPI score at admission were older (p <.001), more frequently women (p <.001) and had higher prevalence of common chronic conditions. After adjustment for age, gender, and diseases, patients included in the MPI-2 and MPI-3 groups had a significantly higher risk for intrahospital mortality (hazard ratio: 3.48, 95% confidence intervals:, p =.047; hazard ratio: 8.31, 95% confidence intervals:, p <.001) than patients included in the MPI-1 group, respectively. In multivariable model, length of stay significantly increased across the three MPI groups (11.29 [0.5], 13.73 [1.3], and 15.30 [1.4] days, respectively [p <.0001]). Conclusions: In older acute care inpatients, MPI score assessed at hospital admission is an independent predictor of in-hospital mortality and the length of hospital stay. © the Author 2014.

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