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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.

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

L’attività di ricerca in corso riguarda la possibilità di ricavare dati clinicamente significativi dai segnali ottici PPG (PhotoPletysmoGraphy). Il segnale PPG viene utilizzato per ricavare informazioni sul volume e sulla saturazione del sangue che interessa il distretto illuminato dalla luce IR (infrarosso) usata per l’analisi. Il volume di sangue contenuto nel segmento di arteria esaminato dipende dalla pressione e dal ciclo cardiaco, attraverso la rigidità dell’arteria.

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.

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.

Objectives Cognitive frailty, a condition describing the simultaneous presence of physical frailty and mild cognitive impairment, has been recently defined by an international consensus group. We estimated the predictive role of a “reversible” cognitive frailty model on incident dementia, its subtypes, and all-cause mortality in nondemented older individuals. We verified if vascular risk factors or depressive symptoms could modify this predictive role. Design Longitudinal population-based study with 3.5- and 7-year of median follow-up. Setting Eight Italian municipalities included in the Italian Longitudinal Study on Aging. Participants In 2150 older individuals from the Italian Longitudinal Study on Aging, we operationalized reversible cognitive frailty with the presence of physical frailty and pre-mild cognitive impairment subjective cognitive decline, diagnosed with a self-report measure based on item 14 of the Geriatric Depression Scale. Measurements Incidence of dementia, its subtypes, and all-cause mortality. Results Over a 3.5-year follow-up, participants with reversible cognitive frailty showed an increased risk of overall dementia [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.02–5.18], particularly vascular dementia (VaD), and all-cause mortality (HR 1.74, 95% CI 1.07–2.83). Over a 7-year follow-up, participants with reversible cognitive frailty showed an increased risk of overall dementia (HR 2.12, 95% CI 1.12–4.03), particularly VaD, and all-cause mortality (HR 1.39, 95% CI 1.03–2.00). Vascular risk factors and depressive symptoms did not have any effect modifier on the relationship between reversible cognitive frailty and incident dementia and all-cause mortality. Conclusions A model of reversible cognitive frailty was a short- and long-term predictor of all-cause mortality and overall dementia, particularly VaD. The absence of vascular risk factors and depressive symptoms did not modify the predictive role of reversible cognitive frailty on these outcomes.

Objective Cognitive frailty is a condition recently defined by operationalized criteria describing the simultaneous presence of physical frailty and mild cognitive impairment (MCI). Two subtypes for this clinical construct have been proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI) and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective cognitive decline). Here the prevalence of a potentially reversible cognitive frailty model was estimated. It was also evaluated if introducing a diagnosis of MCI in older subjects with physical frailty could have an additive role on the risk of dementia, disability, and all-cause mortality in comparison with frailty state or MCI condition alone, with analyses separately performed for inflammatory state. Methods In 2,373 individuals from the population-based Italian Longitudinal Study on Aging with a 3.5-year-follow-up, we operationally categorized older individuals without dementia into four groups: non-frail/non-MCI, non-frail/MCI, frail/non-MCI, and frail/MCI. Results The prevalence of potentially reversible cognitive frailty was 1%, increasing with age and more represented in women than in men, and all groups were associated with significant increased incident rate ratios of dementia, disability, and mortality. A significant difference in rates of disability has been found between the MCI and non-MCI groups (contrasts of adjusted predictions: 0.461; 95% confidence interval: 0.187–0.735) in frail individuals with high inflammatory states (fibrinogen >339 mg/dL). Conclusion In older individuals without dementia and with elevated inflammation, a potentially reversible cognitive frailty model could have a significant additional predictive effect on the risk of disability than the single conditions of frailty or MCI.

Summary Pathohistological alterations of the kidney and pancreas were studied in a group of elderly diabetics divided into “aged diabetics” (AD) (onset of diabetes before 60 years of age) and “senile diabetics” (SD) (onset of diabetes after 70 years of age). The control groups were formed by middle-aged non-insulin dependent diabetics (NIDDM) and non-diabetic elderly subjects. The non-diabetic elderly subjects showed no damage of pancreatic islets and the arterioles were also intact. The middle-aged NIDDM group having had diabetes for less than one year presented no alterations either. Middle-aged NIDDM patients affected by the disease for longer than 10 years, displayed the characteristic diabetic damage (hyalinization of the islets and arteriolar damage). In addition, AD presented pancreatic lesions characteristic of long-term NIDDM. SD were divided into two groups depending on the duration of disease: shorter than 6 and longer than 10 years. The former presented small islets with few fibrotic cells and arteriolar damage, while the latter presented a picture of transition between SD with duration of disease shorter than 6 years and AD. The kidney in AD and SD affected by diabetes longer than 10 years resembled the kidney of NIDDM patients. SD with duration of disease shorter than 6 years had aspecific age-related damage. These lesions seem to confirm that macroangiopathy represents the main pathogenesis of senile diabetes, being aggravated by the persisting hyperglycemia causing microangiopathy.