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San Giovanni Rotondo, Italy

Frisardi V.,Gerontology Geriatrics Research Laboratory
Journal of Alzheimer's Disease | Year: 2012

Apolipoprotein E [ApoE, APOE (gene)] is a multifunctional protein of the lipid and lipoprotein transport system mainly involved in metabolism of dietary lipids. Its polymorphic variants are considered a genetic risk factor of cognitive impairment in several neurodegenerative disorders such as Lewy body dementia, Huntington's disease, and Alzheimer's disease, as well as in vascular dementia and cerebrovascular disease. The precise mechanism by which APOE affects neurodegeneration is still unclear. Epidemiological and experimental studies demonstrated an influence of APOE on metabolic parameters but, to the best of our knowledge, no data are available about the exact role in humans of the effect of APOE on metabolic-cognitive syndrome (MCS). The latter is a model of cognitive impairment linked to metabolic syndrome identifying a grey zone between metabolic disorders and neuropathological process driving late-life cognitive decline. Although it may be a daring project that does not reach a final conclusion because of disease complexity, I hope to elucidate whether APOE may have a prominent role in MCS, going beyond the simple addition of separate mechanisms already known. © 2012 - IOS Press and the authors. All rights reserved.

Pilotto A.,Geriatrics Unit | Pilotto A.,Gerontology Geriatrics Research Laboratory | Sancarlo D.,Gerontology Geriatrics Research Laboratory | Aucella F.,Nephrology Unit and Dialysis Center | And 7 more authors.
Rejuvenation Research | Year: 2012

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. © 2012, Mary Ann Liebert, Inc.

Pilotto A.,Geriatrics Unit | Pilotto A.,Gerontology Geriatrics Research Laboratory | Panza F.,Gerontology Geriatrics Research Laboratory | Sancarlo D.,Gerontology Geriatrics Research Laboratory | And 3 more authors.
Journal of Nephrology | Year: 2012

In older patients, given the central role of prognosis in clinical decision-making, there is an urgent need to develop accurate, validated, and rigorously tested prognostic indices. Current data suggest that in older patients not only physical but also psychological, cognitive, functional, nutritional, biological, and social factors may contribute to the increased risk of negative outcomes including institutionalization, hospital-ization, and mortality. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment that included information from eight domains, i.e. basal and instrumental activities of daily living, cognitive and nutritional status, the risk for pressure sores, comorbidi-ties, drug use, and co-habitation status was effective in predicting short- and long-term all-cause mortality risk in hospitalized patients with various acute and chronic conditions, including chronic kidney disease (CKD). In a consecutive cohort of patients with CKD the MPI accuracy in predicting mortality was significantly higher than the accuracy of the estimated glo-merular filtration rate (eGFR). More recently, findings from hospital-based cohorts suggest that adding MPI information to the eGFR markedly improved the prediction of two-year all-cause mortality in older patients with CKD. While further studies are needed to assess the potential usefulness of this prognostic tool in clinical practice, a multidimensional assessment for all-cause mortality risk prediction should be considered in older patients with CKD. These findings support the concept that considering multidimensional aggregate information is very important for predicting short- and long-term all-cause mortality in older subjects with CKD, and that it may be important for the identification of more suitable management of these patients. © 2012 Società Italiana di Nefrologia.

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.

Pilotto A.,Rehabilitation and Stabilization | Pilotto A.,Geriatrics Unit | Panza F.,University of Bari | Panza F.,Gerontology Geriatrics Research Laboratory | And 19 more authors.
PLoS ONE | Year: 2015

Background: Older adults are often excluded from clinical trials. Decision making for administration of statins to older patients with diabetes mellitus (DM) is under debate, particularly in frail older patients with comorbidity and high mortality risk. We tested the hypothesis that statin treatment in older patients with DM was differentially effective across strata of mortality risk assessed by the Multidimensional Prognostic Index (MPI), based on information collected with the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA). Methods: In this retrospective observational study, we estimated the mortality risk in 1712 community-dwelling subjects with DM ≥ 65 years who underwent a SVaMA evaluation to establish accessibility to homecare services/nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) risk of mortality at baseline and propensity score-adjusted hazard ratios (HR) of three-year mortality were calculated according to statin treatment. Results: Higher MPI-SVaMA scores were associated with lower rates of statin treatment (MPI-SVaMA-1 = 39% vs MPI-SVaMA-2 = 36% vs MPI-SVaMA-3 = 24.9%. p<0.001) and higher three-year mortality (MPI-SVaMA-1 = 12.9% vs MPI-SVaMA-2 = 24% vs MPI-SVaMA-3 = 34.4%, p<0.001). After adjustment for propensity score quintiles, statin treatment was significantly associated with lower three-year mortality irrespective of MPI-SVaMA group (interaction test p = 0.303). HRs [95% confidence interval (CI)] were 0.19 (0.14-0.27), 0.28 (0.21-0.36), and 0.26 (0.20-0.34) in the MPI-SVaMA-1, MPI-SVaMA-2, and MPI-SVaMA-3 groups, respectively. Subgroup analyses showed that statin treatment was also beneficial irrespective of age. HRs (95% CI) were 0.21 (0.15-0.31), 0.26 (0.20-0.33), and 0.26 (0.20-0.35) among patients aged 65-74, 75-84, and ≥ 85 years, respectively (interaction test p=0.812). Conclusions: Statin treatment was significantly associated with reduced three-year mortality independently of age and multidimensional impairment in community-dwelling frail older patients with DM. © 2015 Pilotto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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