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.
Klotho; Chromosome 13; High-density lipoprotein cholesterol; Total cholesterol; Fasting glucose; Fasting insulin; Insulin-like growth factor-1; Hemoglobin; Creatinine; Albumin; Lymphocytes
Cognition has already been considered as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. We estimated the prevalence of frailty syndrome in an Italian older population and its predictive role on all-cause mortality and disability in nondemented subjects and in demented patients. We evaluated 2,581 individuals recruited from the Italian Longitudinal Study on Aging, a population-based sample of 5,632 subjects, aged 65–84 years old. Participants received identical baseline evaluation at the 1st survey (1992–1993) and were followed at 2nd (1995–1996) and 3rd survey (2000–2001). A phenotype of frailty according to partially modified measurement of Cardiovascular Health Study criteria was operationalized. The overall prevalence of frailty syndrome in this population-based study was 7.6% (95% confidence interval (CI) 6.55–8.57). Frail individuals noncomorbid or nondisable were 9.1% and 39.3%, respectively, confirming an overlap but not concordance in the co-occurrence among these conditions. Frailty was associated with a significantly increased risk of all-cause mortality over a 3-year follow-up (hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.52–2.60) and over a 7-year follow-up (HR 1.74, 95% CI 1.44–2.16), but with significant increased risk of disability only over a 3-year follow-up (HR 1.32, 95% CI 1.06–1.86 over a 3-year follow-up and HR 1.16, 95% CI 0.88–1.56 over a 7-year follow-up). Frail demented patients were at higher risk of all-cause mortality over 3- (HR 3.33, 95% CI 1.28–8.29) and 7-year follow-up periods (HR 1.89, 95% CI 1.10–3.44), but not of disability. Frailty syndrome was a short-term predictor of disability in nondemented older subjects and short- and long-term predictor of all-cause mortality in nondemented and demented patients.
Frailty; All-cause mortality; Dementia; Disability; Alzheimer’s disease
Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios (ORs) alone are insufficient to assess these risks. We calculated AD lifetime risk in 7,351 cases and 10,132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68% and 35 % for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age- groups clearly demonstrates that APOE4 is a risk factor not only for late- onset but for early- onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.
The association between angiotensin-converting enzyme (ACE) genotypes and functional decline in older adults remains controversial. To assess if ACE gene variations influences functional abilities at older age, the present study explored the association between the common ACE insertion/deletion (I/D) polymorphism and disability measured with activities of daily living (ADL) in hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I, I/D, and D/D) in a population of 2,128 hospitalized older patients divided according to presence or absence of ADL disability. Logistic regression analysis adjusted for possible confounding factors, identified an association between the I/I genotype with ADL disability (OR = 1.54, 95% CI 1.04–2.29). This association was significant in men (OR = 2.01, 95% CI 1.07–3.78), but not in women (OR = 1.36, 95% CI 0.82–2.25). These results suggested a possible role of the ACE polymorphism as a genetic marker for ADL disability in hospitalized older patients.
Angiotensin-converting enzyme; Disability; Aging; Hospitalized patients
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.
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.
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.
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.
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.
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.
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 ε2 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 ε2 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.
Apolipoprotein E; Mortality; Cardiovascular aging; Dementia
AIM: To evaluate the prevalence of upper gastrointestinal symptoms and their association with clinical and functional characteristics in elderly outpatients.
METHODS: The study involved 3238 outpatients ≥ 60 years consecutively enrolled by 107 general practitioners. Information on social, behavioral and demographic characteristics, function in the activities of daily living (ADL), co-morbidities and drug use were collected by a structured interview. Upper gastrointestinal symptom data were collected by the 15-items upper gastro-intestinal symptom questionnaire for the elderly, a validated diagnostic tool which includes the following five symptom clusters: (1) abdominal pain syndrome; (2) reflux syndrome; (3) indigestion syndrome; (4) bleeding; and (5) non-specific symptoms. Presence and severity of gastrointestinal symptoms were analyzed through a logistic regression model.
RESULTS: 3100 subjects were included in the final analysis. The overall prevalence of upper gastrointestinal symptoms was 43.0%, i.e. cluster (1) 13.9%, (2) 21.9%, (3) 30.2%, (4) 1.2%, and (5) 4.5%. Upper gastrointestinal symptoms were more frequently reported by females (P < 0.0001), with high number of co-morbidities (P < 0.0001), who were taking higher number of drugs (P < 0.0001) and needed assistance in the ADL. Logistic regression analysis demonstrated that female sex (OR = 1.39, 95% CI: 1.17-1.64), disability in the ADL (OR = 1.47, 95% CI: 1.12-1.93), smoking habit (OR = 1.29, 95% CI: 1.00-1.65), and body mass index (OR = 1.06, 95% CI: 1.04-1.08), as well as the presence of upper (OR = 3.01, 95% CI: 2.52-3.60) and lower gastroenterological diseases (OR = 2.25, 95%CI: 1.70-2.97), psychiatric (OR = 1.60, 95% CI: 1.28-2.01) and respiratory diseases (OR = 1.25, 95% CI: 1.01-1.54) were significantly associated with the presence of upper gastrointestinal symptoms.
CONCLUSION: Functional and clinical characteristics are associated with upper gastrointestinal symptoms. A multidimensional comprehensive evaluation may be useful when approaching upper gastrointestinal symptoms in older subjects.
Upper gastrointestinal symptoms; Elderly; Upper gastro-intestinal symptom questionnaire for the elderly; Gastroesophageal reflux disease; Disability
Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies.
Multidimensional impairment of older patients may influence the clinical outcome of diseases. The aim of this study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure.
Methods and Results
In this prospective study with a 1-month follow-up, 376 patients aged 65 and older with a diagnosis of heart failure were enrolled. A standardized comprehensive geriatric assessment that included information on functional (activities of daily living and instrumental activities of daily living), cognitive (Short Portable Mental Status Questionnaire), and nutritional status (Mini Nutritional Assessment), as well as on risk of pressure sore (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale Index), medications, and social support network, was used to calculate the MPI for mortality using a previously validated algorithm. The New York Heart Association, the Enhanced Feedback for Effective Cardiac Treatment, and the Acute Decompensated Heart Failure National Registry regression model scores were also calculated. Higher MPI values were significantly associated with higher 30-day mortality, both in men (MPI-1, 2.8%; MPI-2, 15.3%; MPI-3, 47.4%; P=0.000) and women (MPI-1, 0%; MPI-2, 6.5%; MPI-3, 14.6%; P=0.011). The discrimination of the MPI was also good, with areas under the receiver operating characteristic curves (men: 0.83; 95% CI, 0.75 to 0.90; women: 0.80; 95% CI, 0.71 to 0.89) greater than receiver operating characteristic areas of New York Heart Association (men: 0.63; 95% CI, 0.57 to 0.69; P=0.015; women: 0.65; 95% CI, 0.55 to 0.75; P=0.064), Enhanced Feedback for Effective Cardiac Treatment (men: 0.69; 95% CI, 0.58 to 0.79; P=0.045; women: 0.71; 95% CI, 0.55 to 0.87; P=0.443), and Acute Decompensated Heart Failure National Registry scores (men: 0.65; 95% CI, 0.52 to 0.78; P=0.023; women: 0.67; 95% CI, 0.49 to 0.83, P=0.171).
The MPI, calculated from information collected in a standardized comprehensive geriatric assessment, is useful to estimate the risk of 1-month mortality in older patients with heart failure.
heart failure; mortality; risk factors; Multidimensional Prognostic Index (MPI); prognosis
The only established genetic determinant of non-Mendelian forms of Alzheimer’s disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centres in Belgium, Finland, France, Italy, Spain, Sweden, the UK and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age at onset by interacting with the effect of the ε4 allele of the APOE gene.
To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 (CYP2D6) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD).
This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil 5–10 mg/daily for 6 months. Cognitive and functional statuses were evaluated at baseline and at 6-month follow-up. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Compliance and drug-related adverse events were also evaluated. The analyses identifying the CYP2D6 and APOE polymorphisms were performed in blinded fashion.
At 6-month follow-up, 69 of 115 patients (60%) were responders and 46 patients (40%) were nonresponders to donepezil treatment. A significantly higher frequency of patients with the G allele of rs1080985 was found in nonresponders than in responders (58.7% vs 34.8%, p = 0.013). Logistic regression analysis adjusted for age, sex, Mini-Mental State Examination score at baseline, and APOE demonstrated that patients with the G allele had a significantly higher risk of poor response to donepezil treatment (odds ratio 3.431, 95% confidence interval 1.490–7.901).
The single nucleotide polymorphism rs1080985 in the CYP2D6 gene may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). The analysis of CYP2D6 genotypes may be useful in identifying subgroups of patients with AD who have different clinical responses to donepezil.
= Alzheimer disease;
= Alzheimer’s Disease Assessment Scale–Cognitive Section;
= activities of daily living;
= base pair;
= Clinical Dementia Rating Scale;
= confidence interval;
= cytochrome P450;
= Instrumental Activities of Daily Living;
= International Classification of Diseases, 9th Revision;
= mild cognitive impairment;
= Mini-Mental State Examination;
= National Institute for Health and Clinical Excellence;
= National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association Work Group;
= odds ratio;
= single nucleotide polymorphism.
The role of the apoliprotein E (APOE) and the angiotensin converting enzyme (ACE) polymorphisms on health and functional status deterioration in old age is still undefined. Recently, a Multidimensional Prognostic Index (MPI) for 1-year mortality derived from a Comprehensive Geriatric Assessment (CGA) was developed and validated in hospitalized elderly patients. The aim of this study was to investigate the possible association of the APOE and ACE gene polymorphisms with the multidimensional impairment, as evaluated by the MPI, in older patients. These polymorphisms were assessed in 1894 geriatric inpatients divided into three groups according to their MPI values: MPI-1 low risk (n = 988), MPI-2 moderate risk (n = 671), and MPI-3 severe risk of mortality (n = 235). A slight deviation from Hardy–Weinberg equilibrium was observed for the APOE genotypes. With the increasing of the MPI grade, a significant increase in the frequencies of ε4 allele and the ACE D/D genotype was observed. The APOE ε4+ and ACE D/D genotypes were associated with severe MPI grade (APOE ε4+, odds ration [OR] = 1.79, 95% confidence interval [CI] 1.20–2.67; ACE D/D, OR = 1.42, 95% CI 1.05–1.92). The combined APOE ε4+ and ACE D/D genetic status was associated with higher MPI grade (OR = 2.85, 95% CI 1.75–4.65), without interaction. No significant associations between APOE and ACE polymorphisms and 2-year mortality were found. APOE and ACE genes might predispose individuals to health and functional status deterioration in old age, and their effect is additive.
Multidimensional impairment of older patients may influence the clinical outcome of acute or chronic diseases. Our purpose is to evaluate the usefulness of a multidimensional prognostic index (MPI) based on a comprehensive geriatric assessment (CGA) for predicting mortality risk in older patients with community-acquired pneumonia (CAP).
This prospective study included 134 hospitalized patients aged 65 and older with a diagnosis of CAP. A standardized CGA that included information on clinical, cognitive, functional, and nutritional status as well as comorbidities, medications, and social support network was used to calculate MPI. The pneumonia severity index (PSI) was also calculated. The predictive value of the MPI for all cause mortality over a 1-year follow-up was evaluated and was compared with that of PSI.
Higher MPI values were significantly associated with higher mortality at 30 days (Grade 1 = 3%, Grade 2 = 12%, Grade 3 = 44%, p < .001), 6 months (Grade 1 = 7%, Grade 2 = 21%, Grade 3 = 50%, p < .001), and 1 year (Grade 1 = 10%, Grade 2 = 33%, Grade 3 = 53%, p < .001). A close agreement was found between the estimated mortality by MPI and the observed mortality. MPI had a significant greater discriminatory power than PSI both at 30 days (area under the receiver operating characteristic [ROC] curve = 0.83 vs 0.71, p = .019) and 6 months (0.79 vs 0.69, p = .035), but not after 1 year of follow-up (0.80 vs 0.75, p = .185).
This MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients with CAP into groups at varying risk of short- and long-term mortality. The predictive accuracy of the MPI was higher than the predictive value of the PSI.
Multidimensional prognostic index; Comprehensive geriatric assessment; Pneumonia; Mortality; Elderly people
The role of the apoliprotein E (APOE) and the angiotensin converting enzyme (ACE) polymorphisms on health and functional status deterioration in old age is still undefined. Recently, a Multidimensional Prognostic Index (MPI) for 1-year mortality derived from a Comprehensive Geriatric Assessment (CGA) was developed and validated in hospitalized elderly patients. The aim of this study was to investigate the possible association of the APOE and ACE gene polymorphisms with the multidimensional impairment, as evaluated by the MPI, in older patients. These polymorphisms were assessed in 1894 geriatric inpatients divided into three groups according to their MPI values: MPI-1 low risk (n = 988), MPI-2 moderate risk (n = 671), and MPI-3 severe risk of mortality (n = 235). A slight deviation from Hardy–Weinberg equilibrium was observed for the APOE genotypes. With the increasing of the MPI grade, a significant increase in the frequencies of ɛ4 allele and the ACE D/D genotype was observed. The APOE ɛ4+ and ACE D/D genotypes were associated with severe MPI grade (APOE ɛ4+, odds ration [OR] = 1.79, 95% confidence interval [CI] 1.20–2.67; ACE D/D, OR = 1.42, 95% CI 1.05–1.92). The combined APOE ɛ4+ and ACE D/D genetic status was associated with higher MPI grade (OR = 2.85, 95% CI 1.75–4.65), without interaction. No significant associations between APOE and ACE polymorphisms and 2-year mortality were found. APOE and ACE genes might predispose individuals to health and functional status deterioration in old age, and their effect is additive.
Aim of this study was to evaluate the usefulness of a Multidimensional Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) for predicting mortality risk in older patients with dementia. The present was a retrospective study with a year of follow-up that included 262 patients aged 65 years and older with a diagnosis of dementia. A standardized CGA that included information on clinical, cognitive, functional, and nutritional aspects, as well as comorbidity, medications, and social support network, was used to calculate MPI. The predictive value of the MPI for all-cause mortality over 1 month, 6 months, and 12 months of follow-up was evaluated. Higher MPI values were significantly associated with higher mortality at 1 month (MPI-1, low risk = 0%, MPI-2, moderate risk = 5.2%, MPI-3, severe risk = 13.7%; p < 0.002), 6-months (MPI-1 = 2.7%, MPI-2 = 11.2%, MPI-3 = 28.8%; p < 0.001), and 12-months (MPI-1 = 2.7%, MPI-2 = 18.2%, MPI-3 = 35.6%; p < 0.001) of follow-up. The discrimination of the MPI was also good, with areas under the ROC curves of 0.77 (sensitivity = 82.9%, specificity = 66.0%, with a cut off value > 0.16) at 12-months of follow up. In conclusion, the MPI, calculated from information collected in a standardized CGA, accurately stratified hospitalized elderly patients with dementia into groups at varying risk of short- and long-term mortality.
Comprehensive Geriatric Assessment (CGA); dementia; mortality; Multidimensional Prognostic Index (MPI); prognosis; survival
Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time (acute or chronic) and to the characteristics of the stools (watery, fatty, inflammatory). Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality (over 2.5 million deaths/year in developing countries). Natural and synthetic opiates such as morphine, codeine, and loperamide which react with endogenous opiates (enkephalins, beta-endorphins, dynorphins) mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as loperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, defined according to the Rome criteria, of 9.1%. Infectious diseases (19%) and drug use (16%) were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are poor. At least 75% of those travelling for short periods mention health problems, and in particular traveller’s diarrhoea.
Diarrhoea; Secretory diarrhoeas; Elderly patients; Traveller’s diarrhoea; Antidiarrhoeal drugs; Enkephalinase inhibitor; Racecadotril; Efficacy; Tolerability
The single nucleotide polymorphisms (SNPs) rs449647, rs769446 and rs405509 in the promoter region of the APOE gene have been variously suggested to be ɛ4-independent risk factors for Alzheimer's disease (AD). A previous Italian study found that the rs449647 was significantly associated with late-onset AD. The aim of this study was to verify whether these APOE promoter SNPs are genetic risk factors for AD and to investigate their interaction with the common APOE polymorphism. A total of 169 clinically diagnosed AD patients and 99 cognitively intact age-matched controls were included in the study. Significant associations with AD independent from sex, age and APOE/ɛ4 status were found for rs449647 A/A and rs405509 G/G genotypes (positive), and rs449647 A/T and rs405509 T/T genotypes (negative). Haplotype frequency estimation at the APOE locus showed significant associations for the ATG4, ATT4 and ACG3 (positive) and ATT2, ATT3 and TCG3 (negative) haplotypes. Therefore this study confirms the role of the rs449647 A/A genotype as risk factor for AD in Italy and suggests that promoter genotypes and APOE haplotypes might have a complex function in AD-associated genetic risk factors.
APOE promoter; haplotypes; Alzheimer's disease; genetic risk factors
Our objective was to construct and validate a Multidimensional Prognostic Index (MPI) for 1-year mortality from a Comprehensive Geriatric Assessment (CGA) routinely carried out in elderly patients in a geriatric acute ward. The CGA included clinical, cognitive, functional, nutritional, and social parameters and was carried out using six standardized scales and information on medications and social support network, for a total of 63 items in eight domains. A MPI was developed from CGA data by aggregating the total scores of the eight domains and expressing it as a score from 0 to 1. Three grades of MPI were identified: low risk, 0.0–0.33; moderate risk, 0.34–0.66; and severe risk, 0.67–1.0. Using the proportional hazard models, we studied the predictive value of the MPI for all causes of mortality over a 12-month follow-up period. MPI was then validated in a different cohort of consecutively hospitalized patients. The development cohort included 838 and the validation cohort 857 elderly hospitalized patients. Of the patients in the two cohorts, 53.3 and 54.9% were classified in the low-risk group, respectively (MPI mean value, 0.18 ± 0.09 and 0.18 ± 0.09); 31.2 and 30.6% in the moderate-risk group (0.48 ± 0.09 and 0.49 ± 0.09); 15.4 and 14.2% in the severe-risk group (0.77 ± 0.08 and 0.75 ± 0.07). In both cohorts, higher MPI scores were significantly associated with older age (p = 0.0001), female sex (p = 0.0001), lower educational level (p = 0.0001), and higher mortality (p = 0.0001). In both cohorts, a close agreement was found between the estimated mortality and the observed mortality after both 6 months and 1 year of follow-up. The discrimination of the MPI was also good, with a ROC area of 0.751 (95%CI, 0.70–0.80) at 6 months and 0.751 (95%CI, 0.71–0.80) at 1 year of follow-up. We conclude that this MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients into groups at varying risk of mortality.
The potential usefulness of standardized comprehensive geriatric assessment (CGA) in evaluating treatment and follow-up of older patients with upper gastrointestinal bleeding is unknown.
To evaluate the usefulness of the CGA as a 2-year mortality multidimensional prognostic index (MPI) in older patients hospitalized for upper gastrointestinal bleeding.
Materials and Methods
Patients aged ≥65 years consecutively hospitalized for acute upper gastrointestinal bleeding were included. Diagnosis of bleeding was based on clinical and endoscopic features. All patients underwent a CGA that included six standardized scales, i.e., Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Short Portable Mental Status Questionnaire (SPMSQ), Mini Nutritional Assessment (MNA), Exton-Smith Score (ESS) and Comorbity Index Rating Scale (CIRS), as well as information on medication history and cohabitation, for a total of 63 items. A MPI was calculated from the integrated total scores and expressed as MPI 1 = low risk, MPI 2 = moderate risk, and MPI 3 = severe risk. The predictive value of the MPI for mortality over a 24-month follow-up was calculated.
36 elderly patients (M 16/F 20, mean age 82.8 ± 7.9 years, range 70–101 years) were included in the study. A significant difference in mean age was observed between males and females (M 80.1 ± 4.8 vs. F 84.9 ± 9.3 years; p < 0.05). The causes of upper gastrointestinal bleeding were duodenal ulcer in 38.8%, gastric ulcer in 22.2%, and erosive gastritis in 16.6% of the patients, while 16.6% had gastrointestinal bleeding from unknown origin. The overall 2-year mortality rate was 30.5%. 18 patients (50%) were classified as having a low-risk MPI (mean value 0.18 ± 0.09), 12 (33.3%) as having a moderate-risk MPI (mean value 0.48 ± 0.08) and 6 (16.6%) as having a severe-risk MPI (mean value 0.83 ± 0.06). Higher MPI grades were significantly associated with higher mortality (grade 1 = 12.5%, grade 2 = 41.6%, grade 3 = 83.3%; p = 0.001). Adjusting for age and sex, the prognostic efficacy of MPI for mortality was confirmed and highly significant (odds ratio 10.47, 95% CI 2.04–53.6).
CGA is a useful tool for calculating a MPI that significantly predicts the risk of 2-year mortality in older patients with upper gastrointestinal bleeding.
Comprehensive geriatric assessment; Multidimensional prognostic index; Upper gastrointestinal bleeding; diagnosis