Circulating biomarkers of inflammaging and Alzheimer's disease to track age-related trajectories of dementia: Can we develop a clinically relevant composite combination?

Alzheimer's disease (AD) is a rapidly growing global concern due to a consistent rise of the prevalence of dementia which is mainly caused by the aging population worldwide. An early diagnosis of AD remains important as interventions are plausibly more effective when started at the earliest stages. Recent developments in clinical research have focused on the use of blood-based biomarkers for improve diagnosis/prognosis of neurodegenerative diseases, particularly AD. Unlike invasive cerebrospinal fluid tests, circulating biomarkers are less invasive and will become increasingly cheaper and simple to use in larger number of patients with mild symptoms or at risk of dementia. In addition to AD-specific markers, there is growing interest in biomarkers of inflammaging/neuro-inflammaging, an age-related chronic low-grade inflammatory condition increasingly recognized as one of the main risk factor for almost all age-related diseases, including AD. Several inflammatory markers have been associated with cognitive performance and AD development and progression. The presence of senescent cells, a key driver of inflammaging, has also been linked to AD pathogenesis, and senolytic therapy is emerging as a potential treatment strategy. Here, we describe blood-based biomarkers clinically relevant for AD diagnosis/prognosis and biomarkers of inflammaging associated with AD. Through a systematic review approach, we propose that a combination of circulating neurodegeneration and inflammatory biomarkers may contribute to improving early diagnosis and prognosis, as well as providing valuable insights into the trajectory of cognitive decline and dementia in the aging population.

Polypharmacy and Antibody Response to SARS-CoV-2 Vaccination in Residents of Long-Term Care Facilities: The GeroCovid Vax Study.

BACKGROUND AND OBJECTIVE: Polypharmacy is common in older adults, particularly among those living in long-term care facilities. This condition represents a marker of clinical complexity and might directly affect the immunological response. However, there are limited data on the association of polypharmacy with vaccine immunogenicity. This study evaluated the immune response to anti-SARS-CoV-2 vaccines in older residents of long-term care facilities as a function of the number of medications used. METHODS: In 478 long-term care facility residents participating in the GeroCovid Vax study, we assessed SARS-CoV-2 trimeric S IgG levels through chemiluminescent assays before the vaccination and after 2, 6, and 12 months. A booster dose was administered between 6- and 12-month assessments. Sociodemographic information and data on chronic diseases and medications were derived from medical records. Based on the number of daily medications, residents were classified into the no polypharmacy (zero to four medications), polypharmacy (five to nine medications), and hyperpolypharmacy (ten or more medications) groups. RESULTS: In the sample (mean age 82.1 years, 69.2% female), 200 (41.8%) residents were taking five or fewer medications/day (no polypharmacy), 229 (47.9%) had polypharmacy, and 49 (10.3%) had hyperpolypharmacy. Using linear mixed models adjusted for potential confounders, we found that hyperpolypharmacy was associated with a steeper antibody decline after 6 months from the first vaccine dose administration (ß = - 0.29, 95% confidence interval - 0.54, - 0.03, p = 0.03) than no polypharmacy, while no significant differences were observed at 12 months. CONCLUSIONS: The humoral immune response to SARS-CoV-2 vaccination of older residents showed only slight changes as a function of the number of medications taken. Although it seemed less durable among older residents with hyperpolypharmacy, the booster dose administration equalized such a difference.

Efficacy of COVID-19 control measures on post-vaccination outbreak in Italian Long Term Care Facilities: implications for policies.

Background: Numerous individual and organizational factors can influence the spread of SARS-CoV-2 infection in Long Term Care Facilities (LTCFs). A range of outbreak control measures are still implemented in most facilities involving administrations, staff, residents and their families. This study aims to evaluate which measure could influence the transmission of SARS-CoV-2 infection among residents during the period March 2021-June 2022. Methods: We enrolled 3,272 residents aged ≥60 years. The outbreak control measures adopted to prevent or manage the infection included entry regulations, contact-regulating procedures, and virological surveillance of residents and staff. The association between LTCFs' and participants' characteristics with new cases of COVID-19 infections was analyzed using multilevel logistic regression models. Results: In 33.8% of the facilities 261 cases of SARS-CoV-2 infection were reported. Among participant characteristics, gender and age were not associated with SARS-CoV-2 infection, while having received the vaccine booster dose was protective against infection [Odds Ratio (OR) = 0.34, 95% Confidence Interval (CI) 0.12-0.99, p = 0.048]. In addition, the implementation of protected areas for family visits was associated with a significant reduction of the probability of infections (OR = 0.18, 95% CI 0.03-0.98, p = 0.047). Overall, about 66% of the variability in the probability of SARS-CoV-2 infection during the observational period may be due to facility structure characteristics and 34% to the participant characteristics. Conclusions: These data showed that vaccination booster doses and family visit restriction-control are still needed to make the LTCFs safer against SARS-CoV-2 infection.

Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study.

BACKGROUND AND OBJECTIVES: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. METHODS: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. RESULTS: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. DISCUSSION: The use of trazodone was highly prevalent in functionally dependent and comorbid older adults admitted to LTCF or living at home. Clinical conditions associated with its prescription included depression as well as BPSD.

Efficacy of OM-85 in Recurrent Respiratory Tract Infections.

BACKGROUND: In older patients, prevention of acute respiratory tract infections (RTIs) is challenging. Experimental studies have consistently underlined an immune-potentiating effect of the bacterial lysates product OM85, on both cellular and humoral responses. OBJECTIVE: This work aimed to assess the potential efficacy of OM-85 for RTIs' prevention in older individuals. METHODS: This explorative longitudinal study included 24 patients aged 65 years or older recruited in the GeroCovid Observational Study- home and outpatient care cohort. For the study purposes, we included 8 patients treated with OM-85 from December 2020 to June 2021 (group A), and a control group of 16 patients, matched for sex and age, who did not receive bacterial lysates (group B). RTIs were recorded from the participants' medical documentation in an e-registry from March 2020 to December 2021. RESULTS: In 2020, group A experienced a total of 8 RTIs, which affected 6 out of 8 patients (75%); group B reported 21 RTIs, with at least one event in 11 out of 16 patients (68.7%). In 2021, RTIs affected 2 out of 8 patients (25%) in group A (p < 0.02), and 13 out of 16 patients (81.2%) in group B (within this group, 5 patients had two RTIs). The RTIs' cumulative incidence over the observation period significantly differed between groups (66.7% in group A vs. 24.3% in group B; p < 0.002), as well as the decrease in RTIs frequency from 2020 to 2021. No patients in group A were affected by COVID-19 during the observation period, while among controls, two patients had SARS-CoV-2 infection, notwithstanding three doses of vaccine. CONCLUSION: This study suggests that bacterial lysates may provide clinical benefits for preventing RTIs. Additional research involving larger cohorts is required to verify the effectiveness of OM-85 in preventing RTIs in older adults.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-term Care Facilities: Data From the GeroCovid Vax Study.

OBJECTIVE: Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment. RESEARCH DESIGN AND METHODS: For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents). RESULTS: The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (ß = -0.20; 95% CI -0.34, -0.06) and 6 months (ß = -0.22; 95% CI -0.37, -0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (ß = -0.24; 95% CI -0.43, -0.05 and ß = -0.30; 95% CI -0.50, -0.10, respectively), whereas no differences were observed for those using insulin. CONCLUSIONS: Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.

Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2.

BACKGROUND: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. AIMS: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. METHODS: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. RESULTS: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. DISCUSSION: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. CONCLUSIONS: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population.

Monitoring COVID-19 vaccine use in Italian long term care centers: The GeroCovid VAX study.

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

MicroRNAs modulation and clinical outcomes at 1 year of follow-up in obese patients with pre-diabetes treated with metformin vs. placebo.

BACKGROUNDS: Obese pre-diabetics over express cytokines that influence myocardial function via microRNAs (miRs) expression. OBJECTIVES: To evaluate inflammatory/oxidative stress, miRs' expression and cardiovascular function in obese pre-diabetics assigned to metformin therapy vs. placebo vs. normo-glycemics at 12 months of follow-up. MATERIALS AND METHODS: Eighty-three obese patients after abdominoplastic surgery were divided in pre-diabetics (n 55), normo-glycemics (n 28), and assigned to hypocaloric diet. Pre-diabetics were assigned to metformin (n 23) or to placebo (n 22) plus hypocaloric diet. RESULTS: Obese pre-diabetics in metformin vs. placebo, and obese pre-diabetics with placebo vs. normoglycemics, had significant differences about IMT, MPI, and LVM (p < 0.05). Obese pre-diabetics in metformin vs. placebo showed significant reduction in serum miR-195 and miR-27 (p < 0.05). Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 (p < 0.05). Finally, we found inverse relation between IMT and insulin, HOMA-IR, miR-195, miR-27; between LVEF and Insulin, HOMA-IR, miR-195 and miR-27. We found inverse correlation between LVM and sirtuin-1, Insulin, HOMA-IR, miR-195 and miR-27, and direct correlation with interleukin-6. MPI inversely linked to miR-195 and miR-27. CONCLUSIONS: In obese pre-diabetics', metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27, with reduction in LVM, IMT.

Dietary patterns and cognition in older persons.

PURPOSE OF REVIEW: The current article reviews recently published evidence of the important role that specific dietary patterns may hold on preventing cognitive impairment and dementia over aging. RECENT FINDINGS: Specific dietary patterns attributed to targeting cardiovascular risk factors may protect against the development of mild cognitive impairment (MCI) and dementia, especially Alzheimer's disease. Numerous epidemiological studies have strongly suggested that multinutrient approaches using the Mediterranean diet (Med diet), dietary approach to systolic hypertension (DASH) and the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) are associated with a lower risk of cognitive impairment, MCI and Alzheimer's disease in older persons. This multinutrient approach seems to hold better outcomes than single nutrient intervention. There is only one randomized clinical trial (PREDIMED study) showing an improvement in cognitive performance over time in those undergoing a Med diet protocol. SUMMARY: Nutrition is an essential and modifiable risk factor that plays a role on preventing and/or delaying the onset of dementia. There is sufficient evidence to hypothesize testing neuroprotective dietary patterns on cognition in randomized clinical trials in older persons. Healthy dietary patterns such as the Med diet, DASH and MIND deserve further attention in randomized clinical trials on cognitive performance outcomes.

IAGG/IAGG GARN International Survey of End-of-Life Care in Nursing Homes.

This article reports the findings of a survey on end-of-life (EOL) care in nursing homes of 18 long-term care experts across 15 countries. The experts were chosen as a convenience-based sample of known experts in each country. The survey was administered in 2016 and included both open-ended responses for defining hospice care, palliative care, and "end of life," and a series of questions related to the following areas-attitudes toward EOL care, current practice and EOL interventions, structure of care, and routine barriers. Overall experts strongly agreed that hospice and palliative care should be available in long-term care facilities and that both are defined by holistic, interdisciplinary approaches using measures of comfort across domains. However, it appears the experts felt that in most countries the reality fell short of what they believed would be ideal care. As a result, experts call for increased training, communication, and access to specialized EOL services within the nursing home.

Inappropriate prescription of low molecular weight heparins for thromboprophylaxis among older hospitalized patients.

AIM: To investigate the prevalence and clinical correlates of overprescribing and underprescribing of low molecular weight heparins (LMWHs) for thromboprophylaxis among older medical inpatients. METHODS: Eight hundred seventy six patients (mean age 81.5 ± 7.6 years, female gender 57.2 %) enrolled in a multicenter observational study of seven acute care wards of geriatric medicine in Italy. The risk of venous thromboembolism was ascertained by calculating the Padua score for each patient. Patients receiving appropriate prescription of LMHW during stay were compared to those receiving LMHW with a Padua score <4 (overprescribing group). Similarly, patients with a high thromboembolic risk (Padua score ≥4) but not receiving LMHW (underprescribing group) were compared to patients appropriately not receiving LMHW during stay. Independent correlates of overprescribing and underprescribing were investigated by logistic regression analysis. RESULTS: Overall, 42.8 % of patients had a Padua score ≥4. LMWHs were overprescribed in 7.3 % and underprescribed in 25.2 % of patients. The number of lost basic activities of daily living (BADL) (OR = 0.25; 95 % CI 0.15-0.41) and the number of diagnoses (OR = 0.76; 95 % CI 0.61-0.95) were inversely associated with LMWH overprescription. Conversely, older age (75-84 years: OR = 2.39; 95 % CI 1.10-5.19-85 years or more: OR = 3.25, 95 % CI 1.40-7.61), anemia (OR = 1.80, 95 % CI 1.05-3.16), pressure sores (OR = 4.15, 95 % CI 1.20-14.3), number of lost BADL at the admission (OR = 3.92, 95 % CI 2.86-5.37) and number of diagnoses (OR = 1.29, 95 % CI 1.15-1.44) qualified as significant correlates of LMWH underprescription. DISCUSSION: Underprescription and, to a lesser extent, overprescription still represent an issue among older medical inpatients. CONCLUSION: Implementing risk-stratifying scores into clinical practice may improve appropriateness of LMWHs prescribing during hospitalization.

Awaking Blood Pressure Surge and Progression to Microalbuminuria in Type 2 Normotensive Diabetic Patients.

BACKGROUND: We investigated the predictive value of morning blood pressure surge (MBPS) on the development of microalbuminuria in normotensive adults with a recent diagnosis of type 2 diabetes. METHODS: Prospective assessments of 24-hour ambulatory blood pressure monitoring and urinary albumin excretion were performed in 377 adult patients. Multivariate-adjusted Cox regression models were used to assess hazard ratios (HRs) between baseline and changes over follow-up in MBPS and the risk of microalbuminuria. The MBPS was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. RESULTS: After a mean follow-up of 6.5 years, microalbuminuria developed in 102 patients. An increase in MBPB during follow-up was associated with an increased risk of microalbuminuria. Compared to individuals in the lowest tertile (-0.67 ± 1.10 mmHg), the HR and 95% CI for microalbuminuria in those in the highest tertile of change (24.86 ± 6.92 mmHg) during follow-up were 17.41 (95% CI 6.26-48.42); p for trend <0.001. Mean SD MBPS significantly increased in those who developed microalbuminuria from a mean [SD] of 10.6 [1.4] to 36.8 [7.1], p < 0.001. CONCLUSION: An increase in MBPS is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes.

Tighter glycemic control is associated with ADL physical dependency losses in older patients using sulfonylureas or mitiglinides: Results from the DIMORA study.

BACKGROUND: There is growing evidence that tight glycemic control may be more harmful than beneficial in older persons with Type 2 diabetes (T2DM). It remains controversial if tight glycemic control (lower glycated hemoglobin A1c (A1c)) is associated with functional impairments in older frail patients with T2DM. We explored associations between A1c and losses in Activities of Daily Living (ADLs) in diabetic nursing home (NH) patients and tested for differences according to anti-diabetic treatment: diet, anti-diabetic oral drug (AOD), insulin, combined insulin+AOD. METHODS: We conducted a cross-sectional study on 1845 older NH patients with T2DM from 150 sites across Italy. Complete evaluations on ADLs, glycemic control, anti-diabetic treatments, comorbidities, and clinical data were recorded. ANOVA was applied to compare clinical characteristics across A1c tertiles. Multivariate regression models evaluated associations between A1c and ADL losses. RESULTS: Patients had a mean age [SD]=82 [8] years; BMI=25.5 kg/m(2) [4.7]; Fasting Plasma Glucose (FPG)=7.4 [3.0] mmol/l; Post-prandial glucose (PPG)=10.3 [3.6] mmol/l; A1c=7.0% (54 mmol/mol), ADL losses=3.7 [1.8]. Compared to higher A1c tertiles, patients in the lower tertile had greater ADL losses, were more likely to use AODs, while less likely to use insulin or insulin+AOD. After adjusting for multiple confounders, impairments in ADLs were associated with tighter A1c levels (B=-0.014; p=0.002). Regression models according to anti-diabetic treatment showed that tighter A1c levels continued as independent determinants of ADL losses in patients using AODs (B=-0.023; p=0.001), particularly in those using sulfonylureas (B=-0.043; p<0.001) or mitiglinides (B=-0.044; p=0.050). CONCLUSIONS: Tighter glycemic control was associated with ADL physical dependency losses, especially in those using sulfonylureas and mitiglinides.

Disentangling the Impact of Chronic Kidney Disease, Anemia, and Mobility Limitation on Mortality in Older Patients Discharged From Hospital.

BACKGROUNDS: Chronic kidney disease (CKD), anemia, and mobility limitation are important predictors of mortality. We aimed at investigating the interactions between estimated glomerular filtration rate (eGFR), anemia, and physical performance on 1-year mortality in older patients discharged from acute care hospitals. METHODS: Four hundred and eighty seven patients enrolled in a multicenter, prospective observational study were included in the analysis. eGFR was estimated by the Berlin Initiative Study 1 equation. Anemia was defined on the basis of hemoglobin values. Mobility limitation was rated by the Short Physical Performance Battery (SPPB). Covariates included demographics, nutritional status, cognitive performance, and comorbidity. The outcome of the study was mortality over 1-year follow-up. Interactions among study variables were investigated by survival tree analysis. RESULTS: eGFR < 30 mL/min/1.73 m(2), anemia, and SPPB = 0-4 were significantly associated with mortality, as were hypoalbuminemia and cognitive impairment. Survival tree analysis showed that compared to patients with SPPB ≥ 4 and eGFR ≥ 46.7 mL/min/1.73 m(2) (ie, patients with the least mortality), patients with SPPB < 4 and hemoglobin < 12.2 g/dL had the highest risk of mortality [hazard ratio (HR) = 28.9, 95%CI 10.3-81.2]. Patients with SPPB ≥ 4 and eGFR < 46.7 mL/min/1.73 m(2) and those with SPPB > 4, hemoglobin ≥ 12.2g/dL, and eGFR ≥ 58.6 mL/min/1.73 m(2) had intermediate risk (HR = 6.58, 95%CI = 2.15-20.2, and HR = 15.11, 95%CI=4.42-51.7, respectively). Having SPPB < 4, hemoglobin ≥ 12.2 g/dL, and eGFR<58.6 mL/min/l.73 m(2) was not significantly associated with increased mortality (HR = 2.95, 95%CI = 0.74-11.8). CONCLUSIONS: Interactions among eGFR, anemia, and mobility limitation define different profiles of risk in older patients discharged from acute care hospitals, which deserve to be considered to identify patients needing special care and careful follow-up after discharge.

The Report-AGE project: a permanent epidemiological observatory to identify clinical and biological markers of health outcomes in elderly hospitalized patients in Italy.

BACKGROUND: Italy is expected to experience the largest growth in persons ≥65 years (>20% by 2020). This demographic shift allows for geriatric research on predictive clinical and biological markers of outcomes related to frailty, re-hospitalization and mortality. AIMS: To describe rationale and methods of the Report-AGE study project of acute care patients in Italian National Research Center on Aging (INRCA) research hospitals. METHODS: Report-AGE study is a large observational study on health conditions and outcomes of hospitalized elderly patients (≥65 years). The primary objective of the study is to create a high-level data resource of demographics, comprehensive geriatric assessments, clinical and diagnostic information, as well as biological and molecular markers in all older patients admitted to INRCA Hospitals. Assessments in physical and nutritional parameters, co-morbid health conditions, and associations with frailty parameters are ongoing in older hospitalized adults following an acute event. Study collection began in September 2011. RESULTS: Up to date, there are 3479 patients ≥65 years (mean age: 85 ± 7years) with 1543 men and 1936 women enrolled. Data have been recorded regarding functional and clinical parameters before, during hospital admission and at discharge. Data collection for primary outcome analyses related to re-hospitalization and mortality is estimated for September 2016. DISCUSSION: This study aims at collecting precise clinical data, comprehensive geriatric assessment, risk factors, and biological data from acute care patients. Data will also be used to identify mechanisms underlying frailty in this specific population. CONCLUSION: This study provides a descriptive epidemiological collection of the health conditions of older in-patients.

Severe hypoglycemia is associated with antidiabetic oral treatment compared with insulin analogs in nursing home patients with type 2 diabetes and dementia: results from the DIMORA study.

OBJECTIVES: Severe hypoglycemia is associated with cognitive decline and dementia in older persons with type 2 diabetes. The role of antidiabetic treatments on severe hypoglycemia is unknown in dementia. The aims were to determine the prevalence of severe hypoglycemic events and investigate associations among severe hypoglycemic and specific antidiabetic treatments (classes of oral agents and types of insulin analogs) in a large sample of nursing home patients with diabetes according to dementia status. DESIGN: Cross-sectional observational study. SETTING: A total of 150 nursing homes across Italy. PARTICIPANTS: A total of 2258 patients with type 2 diabetes (dementia = 1138, no dementia = 1120). MEASUREMENTS: Diagnosis of dementia before nursing home admission. Data were collected regarding functional status, glycemic control, antidiabetic treatments, comorbidities, and biochemical and clinical measurements. Logistic regression models with severe hypoglycemia as the dependent variable were used to test associations with antidiabetic agents. RESULTS: Patients had a mean age (SD) of 82 (8) years, body mass index (BMI) of 25.4 (4.8), fasting plasma glucose (FPG) of 7.5 (3.0) mmol/L, postprandial glucose (PPG) of 10.3 (3.6) mmol/L, HbA1c of 7.1% (54 mmol/L), and impairments in activities of daily living (ADLs) of 3.7 (2.1). Severe hypoglycemia was more prevalent in patients with dementia (18%) compared with patients without dementia (8%). Patients with dementia were older, showed greater ADL impairments, greater number of comorbidities, lower FPG, and higher PPG compared with those without dementia. Adjusted logistic regression models in patients with dementia showed that rapid- and long-acting insulin analogs were associated with reduced odds ratio (OR) (OR 0.333; 95% confidence interval [CI] 0.184-0.602; OR 0.248, 95% CI 0.070-0.882, respectively), whereas sulphonylureas and combined metformin + sulphonylurea were associated with increased ORs (OR 8.805, 95% CI 4.260-18.201; OR 6.639; 95% CI 3.273-14.710, respectively) of experiencing severe hypoglycemia. No correlations were found in patients without dementia. CONCLUSION: In older nursing home patients with type 2 diabetes, severe hypoglycemia was significantly higher in dementia. Our findings suggest that sulphonylureas should be used with caution, whereas rapid- and long-acting insulin analogs seem safer.