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Background Cardiac arrhythmias are common conditions in older people. Unfortunately, there is limited literature on associations between cardiac arrhythmias and physical performance or disability. We therefore aimed to prospectively investigate associations between cardiac arrhythmias and changes in disability and physical performance during 8 years of follow-up, using data from the Italian Longitudinal Study on Aging (ILSA). Methods Cardiac arrhythmias diagnosis was posed through a screening phase, confirmed by a physician. The onset of disability in activities of daily living (ADL) and the changes in several physical performance tests during follow-up were considered as outcomes. Fully-adjusted and propensity-score Cox Proportional Hazard models and mixed models were used for exploring associations between cardiac arrhythmia and the outcomes of interest. Results The prevalence of cardiac arrhythmia at baseline was 23.3%. People reporting cardiac arrhythmia at the baseline were significantly older, more frequently male, smokers and reported a higher presence of all medical conditions investigated (hypertension, heart failure, angina, myocardial infarction, diabetes, stroke), but no difference in dementia, Parkinsonism, cognitive or mood disorder. Cardiac arrhythmia at baseline was significantly associated with the incidence of disability in ADL (HR = 1.23; 95%: CI: 1.01-1.50; P = 0.0478 in propensity score analyses; HR = 1.28; 95% CI: 1.01-1.61; P = 0.0401 in fully adjusted models). Cardiac arrhythmia at baseline was also associated with a significant worsening in balance test (P = 0.0436). Conclusions The presence of cardiac arrhythmia at baseline was associated with a significant higher risk of disability and of worsening in some physical performance tests, particularly those relating to balance. Screening and frequently assessing physical performance in older people affected by cardiac arrhythmia can be important to prevent a loss of physical performance, with further, potential, complications of medical management. © 2020 JGC All rights reserved

Background:Gender differences for incidence of dementia among elderly people have been usually investigated considering gender as a predictor and not as a stratification variable.Methods:Analyses were based on data collected by the Italian Longitudinal Study on Aging (ILSA), which enrolled 5,632 participants aged 65–84 years between 1992 and 2000. During a median follow-up of 7.8 years, there were 194 cases of incident dementia in the participants with complete data. Cox proportional hazard models for competing risks, stratified by sex, were defined to determine risk factors in relation to developing dementia.Results:The incidence rate of dementia increased from 5.57/1,000 person-years at 65–69 years of age to 30.06/1,000 person-years at 80–84 years. Cox proportional hazard models for competing risks of incidence of dementia and death revealed that, among men, significant risk factors were heart failure, Parkinson's disease, family history of dementia, mild depressive symptomatology and age, while triglycerides were associated with a lower risk of developing dementia. Significant risk factors in women were age, both mild and severe depressive symptomatology, glycemia ≥109 mg/dL, and a BMI < 24.1 kg/m2. Even as little as three years of schooling was found to be a significant protective factor against the incidence of dementia only for women.Conclusions:Our results suggest that there is an effect modification by gender in our study population in relation to the association between low education level, lipid profile, BMI, and glycemia and dementia.

Background Frailty is a clinical syndrome generally associated with a greater risk for adverse outcomes such as falls, disability, institutionalization, and death. Cognition and dementia have already been considered as components of frailty, but the role of frailty as a possible determinant of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) has been poorly investigated. We estimated the predictive role of frailty syndrome on incident dementia and its subtypes in a nondemented, Italian, older population. Methods We evaluated 2581 individuals recruited from the Italian Longitudinal Study on Aging sample population consisting of 5632 subjects aged 65 to 84 years and with a 3.9-year median follow-up. A phenotype of frailty according to a modified measurement of Cardiovascular Health Study criteria was operationalized. Dementia, AD, and VaD were classified using current published criteria. Results Over a 3.5-year follow-up, 65 of 2581 (2.5%) older subjects, 16 among 252 frail individuals (6.3%), of which 9 were affected by VaD (3.6%), developed overall dementia. In a proportional hazards model, frailty syndrome was associated with a significantly increased risk of overall dementia (adjusted hazard ratio: 1.85; 95% confidence interval: 1.01–3.40) and, in particular, VaD (adjusted hazard ratio: 2.68; 95% confidence interval: 1.16–7.17). The risk of AD or other types of dementia did not significantly change in frail individuals in comparison with subjects without frailty syndrome. Conclusion In our large population-based sample, frailty syndrome was a short-term predictor of overall dementia and VaD.

Midlife elevated blood pressure and hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia. We sought to estimate whether angiotensin-converting enzyme inhibitors (ACE-Is) reduced the risk of developing mild cognitive impairment (MCI) in cognitively normal individuals. In the Italian Longitudinal Study on Aging, we evaluated 1,445 cognitively normal individuals treated for hypertension but without congestive heart failure from a population-based sample from eight Italian municipalities with a 3.5-year follow-up. MCI was diagnosed with current clinical criteria. Dementia, AD, and vascular dementia were diagnosed based on DSM-IIIR criteria, NINCDS–ADRDA criteria, and ICD-10 codes. Among 873 hypertension-treated cognitively normal subjects, there was no significant association between continuous exposure to all ACE-Is and risk of incident MCI compared with other antihypertensive drugs [hazard ratio (HR), 0.45, 95% confidence interval (CI), 0.16–1.28]. Captopril exposure alone did not significantly modify the risk of incident MCI (HR, 1.80, 95% CI, 0.39–8.37). However, the enalapril sub-group alone (HR, 0.17, 95% CI, 0.04 –0.84) or combined with the lisinopril sub-group (HR, 0.27, 95% CI, 0.08–0.96), another ACE-I structurally related to enalapril and with similar potency, were associated with a reduced risk of incident MCI. Study duration exposure to ACE-Is as a “class” was not associated with incident MCI in older hypertensive adults. However, within-class differences linked to different chemical structures and/or drug potencies may exist, with a possible effect of the enalapril and lisinopril sub-groups in reducing the risk of incident MCI.

We investigated the relationship of metabolic syndrome (MetS) and its individual components with incidence of mild cognitive impairment (MCI) and its progression to dementia in a large longitudinal Italian population-based sample with a 3.5-year follow-up. A total of 2097 participants from a sample of 5632 65-84-year-old subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. MCI, dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were classified using current published criteria. Among MCI patients those with MetS (N=49) had a higher risk of progression to dementia (HR, 4.40; 95% CI, 1.30-14.82) compared with those without MetS (N=72). After a multivariate adjustment, the risk in MCI patients with MetS approximately doubled (multivariate adjusted HR, 7.80, 95% CI 1.29-47.20) compared with those MCI without MetS. Finally, among non-cognitively impaired individuals there were no significant differences in risks of developing MCI in those who were affected by MetS (N=608) in comparison with those without MetS (N=837), as well as excluding those individuals with undernutrition or low inflammatory status with or without undernutrition. In our population, among MCI patients the presence of MetS independently predicted an increased risk of progression to dementia over 3.5 years of follow-up.

ACKGROUND: Preclinical cognitive changes may predict an increased risk of dementia, allowing selection of subgroups as possible targets for preventive or therapeutic interventions. OBJECTIVE: To evaluate the predictive effect of daily functioning and motor performance (MP) on the progression to dementia in normal cognition, cognitive impairment, no dementia (CIND), and mild cognitive impairment (MCI). METHODS: The Italian Longitudinal Study on Aging is a large population-based survey on age-related diseases of the cardiovascular and nervous systems. After the baseline assessment, to detect prevalent cases of cognitive impairment and dementia, participants were re-examined at 4-year and 8-year follow-ups. Functional independence was evaluated using the Index of Activities of Daily Living (ADL) and the Instrumental Activities of Daily Living (IADL) Scale. A six-test battery was used to assess MP. RESULTS: Overall, 2,386 individuals were included, for a total of 16,545 person-years. Eight-year incidence of dementia (per 1,000 person-years) was 12.69 in total sample, 9.86 in subjects with normal cognition at baseline, 22.99 in CIND, and 21.43 in MCI. Progression to dementia was significantly higher with increasing baseline ADL and IADL impairment, and with a worse MP. In Cox regression analyses controlled for demographics and major age-related conditions, increased IADL impairment was the stronger predictor of progression to dementia (p

Background and purpose The lack of a wide implementation of stroke units (SU)s in Italy appears to accompany the underuse of the operating units. Community awareness of acute stroke care options may affect stroke resource use. Our aim was to determine the level of knowledge about SUs and tissue-plasminogen activator (t-PA) treatment amongst Italian adults and investigate its relationship to local stroke services implementation. Methods A nation-based telephone survey was carried out in a sample of 1000 residents aged >18 years in May–June 2010. The questionnaire included close-ended questions regarding knowledge of SUs and t-PA treatment. Number and location of both SUs and t-PA treatments were provided by a concurrent national hospital-based survey. The prevalence and distribution of acute stroke care awareness in the community was examined and multivariate analyses were generated. Results Amongst the 1000 participants (474 men, mean age 48.8 ± 17.2), only 26.2% reported knowing about the availability of t-PA treatment and only 15% were aware of the existence of SUs. Awareness of both SUs and t-PA was significantly associated only with education. These associations remained significant in the multivariate analyses. The degree of stroke services implementation (in terms of SUs/inhabitant rates and number of t-PA treatments) was not associated with SU and t-PA awareness. Conclusions This is the first European study that explored public knowledge about t-PA treatment and SUs. Italian adults proved insufficiently educated about SUs and t-PA; there is no higher awareness in areas with a greater supply of stroke services. This might partially explain the underuse of Italian SUs.

The Ottawa Stroke Trials Registry (OSTR) collects information on all randomized controlled trials (RCTs), in all languages, in which the primary focus is stroke. Published trials are added to the registry database once they have been identified by volunteers hand searching journals. We undertook this study to assess volunteer sensitivity, specificity, positive and negative predictive values, accuracy and reliability in identifying RCTs. Three volunteers participated in this study. The complete contents of five years of one journal were searched (n = 240) as were ten research reports from five journals. Volunteer sensitivity, specificity, positive and negative predictive values, and accuracy was 89.5%, 100%, 100%, 99.1%, and 99% respectively. Inter volunteer reliability was 0.87. Searching the published literature to identify RCTs is an enormous task. These results indicate that volunteers, with minimal training, can effectively contribute to this endeavour.

We prospectively examined whether vascularfactors are related to an increased incidence of ChronicIdiopathic Distal Symmetric Neuropathy (CI-DSN) in anon-diabetic elderly population. In 8 Italian municipalities,2,512 men and women without both diabetes and CI-DSNat baseline are examined. Potential effect of vascular fac-tors was estimated by regressing new onset CI-DSN on theoccurrence of several vascular diseases and risk factors.Multivariate relative risks of CI-DSN were estimated byCox proportional hazards models. After 3.8 (±2.4) years offollow-up, we documented 51 incident CI-DSN cases. Atunivariate analysis, age, comorbidity, waist circumference,leg length, peripheral artery disease, and coronary heartdisease proved to increase the risk of developing CI-DSN.By multivariate analyses, only age (RR=1.08; 95 % CI,1.02–1.14), leg length (RR=1.05; 95 % CI, 1.01–1.1) andperipheral artery disease (RR=2.75; 95 % CI, 1.15–6.56)proved significant predictors of CI-DSN. Separate analysesby gender show that age is an independent predictor of CI-DSN both in men and in women, while PAD predicts thedisease only in men, together with body height. Incidenceof CI-DSN is higher in individuals carrying vascular con-ditions. In men, the presence at baseline of peripheralartery disease is associated with a threefold increase in therisk of developing CI-DSN. The incidence of neuropathy innon-diabetic individuals is associated with potentiallymodifiable vascular factors.

BackgroundDepression is recognized as being associated with increased mortality. However, there has been little previous research on the impact of longitudinal changes in late-life depressive symptoms on mortality, and of their remission in particular.MethodAs part of a prospective, population-based study on a random sample of 5632 subjects aged 65–84 years, with a 10-year follow-up of vital status, depressive symptoms were assessed by the 30-item Italian version of the Geriatric Depression Scale (GDS). The number of participants in the GDS measurements was 3214 at baseline and 2070 at the second survey, 3 years later. Longitudinal changes in depressive symptoms (stable, remitted, worsened) were examined in participants in both evaluations (n=1941). Mortality hazard ratios (MHRs) according to severity of symptoms and their changes over time were obtained by means of Cox proportional hazards regression models, adjusting for age and other potentially confounding factors.ResultsSeverity is significantly associated with excess mortality in both genders. Compared to the stability of depressive symptoms, a worsened condition shows a higher 7-year mortality risk [MHR 1.46, 95% confidence interval (CI) 1.15–1.84], whereas remission reduces by about 40% the risk of mortality in both genders (women MHR 0.55, 95% CI 0.32–0.95; men MHR 0.59, 95% CI 0.37–0.93). Neither sociodemographic nor medical confounders significantly modified these associations.ConclusionsConsistent with previous reports, the severity and persistence of depression are associated with higher mortality risks. Our findings extend the magnitude of the association demonstrating that remission of symptoms is related to a significant reduction in mortality, highlighting the need to enhance case-finding and successful treatment of late-life depression.

Background/Objectives: Although there is plenty of evidence of the association between metabolic syndrome (MS) and cardiovascular disease, the relationship between alcohol consumption and MS is still questioned. The few publications with respect to the elderly seem to indicate that alcohol consumption is unassociated with MS. The aim of this study was to assess the association between alcohol consumption and the prevalence and incidence of MS, as well as its components in a large sample of Italian elderly people. Subjects/Methods: This is a multicenter study on a population-based sample of Italian people aged 65–84 years. The Italian Longitudinal Study on Aging (ILSA) included a prevalence phase in 1992 and an incidence phase from 1995 to 1996. The median length of follow-up was 3.5 years. In the present study, the analysis included 1321 men grouped into five alcohol consumption classes: abstainers, and those consuming p12, 13–24, 25–47 or X48 g of alcohol in a day. Among the 1122 women considered, the last two of the above five categories were pooled together (424 g/day). MS was defined according to ATP III criteria. All statistical analyses were stratified by gender. Results: Adjusted odds ratios showed that categorized alcohol consumption was not significantly associated with the prevalence and incidence of MS when compared with abstainers in either gender. For the MS incidence survey, three of five components (systolic pressure, glycemia and waist circumference) proved to be significantly and harmfully affected by alcohol consumption in males, whereas no such significant association emerged in females. Conclusions: These results suggest that alcohol can modify an individual’s metabolic condition and that, even among the elderly, men might be more sensitive to the effects of alcohol than women.

Objective The authors investigated the relationship of metabolic syndrome (MetS) and its individual components with incident dementia in a prospective population-based study with a 3.5-year follow-up. Methods A total of 2097 participants from a sample of 5632 subjects (65e84 years old) from the Italian Longitudinal Study on Ageing were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Dementia, Alzheimer disease (AD) and vascular dementia (VaD) were classified using current published criteria. Results MetS subjects (N¼918) compared with those without MetS (N¼1179) had an increased risk for VaD (1.63% vs 0.85%, adjusted hazard ratio (HR) 3.71, 95% CI 1.40 to 9.83). After excluding 338 subjects with baseline undernutrition, MetS subjects compared with those without MetS had an elevated risk of VaD (adjusted HR, 3.82; 95% CI 1.32 to 11.06). Moreover, those with MetS and high inflammation had a still further higher risk of VaD (multivariate adjusted HR, 9.55; 95% CI 1.17 to 78.17) compared with those without MetS and high inflammation. On the other hand, those with MetS and low inflammation compared with those without MetS and low inflammation did not exhibit a significant increased risk of VaD (adjusted HR, 3.31, 95% CI 0.91 to 12.14). Finally, a synergistic MetS effect versus its individual component effects was verified on the risk of VaD. Conclusion In our population, MetS subjects had an elevated risk of VaD that increased after excluding patients with baseline undernutrition and selecting MetS subjects with high inflammation.

Background and aims: A protective effect of moderate alcohol consumption on the cardiovascular system has consistently been reported, but limited evidence has been produced on the association of alcohol with metabolic factors in the elderly. The aim of this study was to investigate the association between different levels of current alcohol consumption and cardiovascular risk factors in a representative sample of elderly Italian men, mainly wine drinkers. Methods and results: This is a cross-sectional multi-centre study on a population-based sample of Italian men aged 65e84 years, drawn from the Italian Longitudinal Study on Aging (ILSA) cohort. The analyses included 1896 men. Almost all the drinkers (98%) drank wine as a lifelong habit. Adjusted ORs for risk levels for cardiovascular factors (BMI, waist circumference, fibrinogen, a2 protein, white blood cells, HDL cholesterol, Apo A-I, total cholesterol, Apo B-I, triglycerides, LDL, glycated hemoglobin, insulin, fasting plasma glucose, HOMA IR, systolic and diastolic blood pressure) were estimated, comparing drinkers with teetotalers using multivariate logistic regression models. We found alcohol consumption in older age associated with healthier hematological values of fibrinogen, HDL cholesterol, Apo A-I lipoprotein and insulin, but it was also associated with a worse hematological picture of total, LDL cholesterol levels, and systolic pressure. Conclusion: Our results indicated in elderly moderate wine drinkers a noticeably safe metabolic, inflammatory and glycemic profile that might balance higher blood pressure, leading to a net benefit. These findings however need to be placed in relation to the known adverse social and health effects of heavy drinking.

Aims: To assess the role of type 2 diabetes as a risk factor for cognitive decline among elderly people. Methods: Analyses were carried out on data from the Italian Longitudinal Study on Aging, a study on 5,632 subjects aged 65–84 years, with baseline in 1992 and follow-ups in 1996 and 2000. Results: At baseline, diabetic women had significantly worse scores on all cognitive tests compared to nondiabetic women, but did not show worsening over time, whereas men with diabetes did not show worse scores on cognitive tests at baseline compared to nondiabetic males; however, diabetes in men was associated with a risk of cognitive decline over time, particularly in attention. Higher levels of HbA 1c were associated with poorer performance on memory tests at follow-up in both sexes. Conclusion: The impact of diabetes on cognitive status might differ in older men and women, probably because of a survival effect, with a higher mortality at a younger age among diabetic men. The metabolic and cardiovascular abnormalities associated with diabetes might be responsible for the cognitive decline, at different rates and ages, in men and women. The routine assessment of diabetes complications in the elderly should include cognitive evaluation in both sexes.

Objectives: Depressive symptoms (DS) are very frequent in elderly individuals and are associated with negative outcomes. This study was undertaken to evaluate whether DS predict physical disability in this population. Methods: A prospective, community-based cohort study, this work included 5,632 individuals aged 65–84 years, who were recruited from the demographic registries of eight Italian municipalities in 1992. The complete data of 3,256 subjects were collected and analyzed. DS were assessed using the Geriatric Depression Scale with a score 10/30 indicating DS. All traditional risk factors for disability established by questionnaires and physical examinations were assessed at baseline. The outcomes were self-reported disability on the activities of daily living (ADL) test and the performance-based physical function assessment (Physical Performance Tests, PPT). The contribution of the predictive variables to the outcomes evaluated after a mean follow-up of 3.5 0.4 years was assessed using hierarchical logistic nested models. Results: Baseline DS was associated with higher rates of ADL disability (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.12–2.66) and PPT disability (OR 1.83, 95% CI 1.17–2.85) in men and with ADL disability (OR 1.81, 95% CI 1.28 –2.55) in women. The independent predictors of PPT disability in women were arthritis (OR 2.13, 95% CI 1.28 –3.53) and age (OR 1.09; 95% CI 1.03–1.15). Conclusions: This study provides evidence that older persons who report DS are at higher risk of subsequent physical decline. In women, arthritis is a more powerful predictor of preclinical disability, as measured by PPT.

Aims: We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI. Methods: A total of 2,963 individuals from a sample of 5,632 65- to 84-year-old subjects were cognitively and functionally evaluated at the 1st and 2nd surveys of the Italian Longitudinal Study on Aging, a prospective cohort study with a 3.5-year follow-up. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale. Results: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed at the 1st survey. During the 3.5-year follow-up, 105 new events of MCI were diagnosed. We did not observe any significant association between depressive symptoms and incident MCI (RR = 1.25, 95% CI = 0.85–1.84, 2 = 1.30, p ! 0.25). No sociodemographic variables or vascular risk factors modified the relationship between depressive symptoms and incident MCI. Conclusion: In our population, depressive symptoms were not associated with the rate of incident MCI. Our findings did not support a role of sociodemographic variables or vascular risk factors in the link between depressive symptoms and incident MCI.

In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months.A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate.The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).

OBJECTIVE To assess the feasibility, safety and preliminary efficacy of intra-arterial thrombolysis (IAT) compared with standard intravenous thrombolysis (IVT) for acute ischemic stroke. METHODS Eligible patients with ischemic stroke, who were devoid of contraindications, started IVT within 3 h or IAT as soon as possible within 6 h. Patients were randomized within 3 h of onset to receive either intravenous alteplase, in accordance with the current European labeling, or up to 0.9 mg/kg intra-arterial alteplase (maximum 90 mg), over 60 min into the thrombus, if necessary with mechanical clot disruption and/or retrieval. The purpose of the study was to determine the proportion of favorable outcome at 90 days. Safety endpoints included symptomatic intracranial hemorrhage (SICH), death and other serious adverse events. RESULTS 54 patients (25 IAT) were enrolled. Median time from stroke onset to start to treatment was 3 h 15 min for IAT and 2 h 35 min for IVT (p