Italian Longitudinal Study Research Articles

Physical disability among older Italians with diabetes. The ILSA Study

We studied the role of diabetic complications and comorbidity in the association between diabetes and disability in the elderly. Data were from a nationally representative sample of 5632 older Italians, aged 65 years and older, and who participated in the Italian Longitudinal Study on Aging. Clinical diagnoses of diabetes and other major chronic conditions were made by a physician, while disability was assessed by self-reported information on activities of daily living and physical performance tests. After adjusting for age, education and BMI, disability on the basis of activities of daily living was associated with diabetes in women, but not in men (odds ratio [OR] 1.65, CI: 1.22-2.23 and OR 1.21, CI: 0.84-1.75 respectively). In contrast, the association between severe and/or total disability on the basis of physical performance tests and diabetes was strong in both sexes (OR 2.81, CI: 1.44-5.41 and OR 2.16, CI: 1.25-3.73 respectively). Adjusting for traditional complications and comorbidity reduced the excess odds of disability by 38% in women and by 16% in men. Disability in older Italians with diabetes is frequent and only partially attributable to traditional diabetic complications and comorbidity.

QT dispersion in the elderly. The ILSA Study

In the last few years there has been active interest in the study of QT interval dispersion (QT-d) calculated from the 12-lead ECG, as a non-invasive method of investigating the homogeneity of ventricular recovery time. The aim of this study was to evaluate QT interval dispersion, analyzing in particular gender and age relationships. Discussion of its electrophysiologic and clinic meaning is still open; moreover, the method must be standardized and normal values should be clearly defined. The two common indices, range and standard deviation of QT, were taken into account. The study sample is part of the population-based Italian Longitudinal Study on Aging (ILSA) with individuals older than 64 years. Three groups were identified by clinical data: 256 healthy subjects, 98 patients with only cardiac diseases, and 472 patients with only hypertension. Age (< 75 and > 75) and gender subgroups were considered, showing that age and gender influence the QT-d differently in the three groups. QT-d indices were influenced in the healthy group by gender (p < 0.001), in the cardiopathy group by age (p < 0.001), and in the hypertension group by age (p < 0.02) and gender (p < 0.01). Then the two gender groups were considered separately. In the female group, QT-d increased significantly with age only in the healthy group (p < 0.02), whereas in the male group it increased significantly in the cardiopathy and hypertension groups (p < 0.01). The two QT-d indices behaved in a very similar way in all the comparisons. In older people, gender and age influenced the three clinical selected groups differently. However, it was shown that is not possible to indicate a clear, definite threshold value classifying with accuracy a single subject in the clinical groups; and a clear-cut, direct clinic application is still doubtful.

Risk factors and health determinants in older Italians.

According to a WHO estimate, 50% of the total burden of diseases in men and 25% in women for the EURO-A group (which includes the highly developed countries of the WHO European Region) are attributable to unhealthy life-styles. The aim of the present study was to analyze anthropometric, biochemical and behavioral risk factors using data from the Italian Longitudinal Study on Aging (ILSA), a population-based study of older Italians initiated in 1992 to study those chronic conditions and attendant risk factors that contribute most substantially to morbidity, disability and mortality. In this descriptive study, we calculated the means and distribution of risk factors in a sample of 5632 Italian subjects aged 65-84 by gender, age class and geographic area, and identified the proportion of these subgroups at higher risk. Analyses include data from the first (1992-93) and second (1995-96) examinations of this cohort. Over 64% of older Italian participants were overweight in 1992. More than 70% had blood pressure in the borderline or definitely hypertensive range, and almost one-third had hyperlipidemic serum cholesterol levels, including subjects receiving treatment for these conditions. Based on Body Mass Index, more women than men were obese (27 vs 15%) and more women than men were hyperlipidemic in all age classes (38 vs 23%). Approximately 13% of the sample had glucose levels exceeding the recommended 126 mg/dL. Men were found to consume on average about 41 grams of alcohol daily and women 17 g/d. Lastly, we found that approximately 20% of men and 8% of women were smokers in 1992 but that smoking tended to diminish with age. As the Italian population rapidly ages, the burden of disease and disability is increasing, necessitating more focused, immediate and effective prevention programs. We have identified a number of critical concerns ripe for intervention. The results of this study can better focus such efforts and help guide long-term health planning and policy.

Lifestyle-related risk factors for Parkinson's disease: a population-based study.

To investigate the association of major lifestyle-related risk factors with the prevalent cases of Parkinson's disease (PD) identified by the Italian Longitudinal Study on Aging. A total of 5632 individuals randomly selected from the population registers of eight centers were screened for parkinsonism using both a questionnaire and a neurologic examination. Screened positives underwent a structured clinical work-up for the diagnosis of parkinsonism and parkinsonism subtypes. We identified 113 prevalent cases of PD. Age, male gender, and pesticide-use license were significantly related to PD. Heavy smoking was inversely related to PD. Age (OR = 1.1; 95% CI, 1.06-1.15) and pesticide-use license (OR = 3.7; 95% CI, 1.6-8.6) kept their significant correlation with the disease in the multivariate analysis to adjust for all the variables under investigation. Multivariate analyses were made for men and women separately: pesticide exposure was positively associated with PD only in men. Pesticide exposure might represent a candidate for environmental factors involved in PD.

Stroke in an Elderly Population: Incidence and Impact on Survival and Daily Function

Background: Epidemiological data are essential to estimate the burden of stroke.We evaluated stroke incidence in older Italians and the effect of first-ever stroke on survival and activities of daily living (ADL). Methods: The analysis was performed in the Italian Longitudinal Study on Aging (ILSA) sample, consisting of 5,632 individuals aged 65–84. The ILSA aims at major cardiovascular and neurological age-associated diseases. The baseline survey was performed in 1992 to detect prevalent diseases. The longitudinal examination started on September 1995 aiming at incidence, function and survival. Results: Complete follow-up data were achieved for 77% of the baseline stroke-free cohort (4,164 persons; 50.9% males; mean age 74.5 ± 5.7 years). Incidence for first-ever stroke was 9.51 (95% CI: 7.75–11.27) per 1,000 person years and 12.99 (95% CI: 10.99–14.98) including recurrent stroke (total incidence). Crude mortality was 49.2% among first stroke patients and 15% among persons without stroke. The first-ever stroke mortality risk ratio, adjusted for demographics and comorbidity, was 2.40 (95% CI: 1.62–3.54). In survivors, impairment of at least one ADL was present in 67.6% of first-ever stroke patients vs. 31.6% of individuals without stroke. The comorbidity-adjusted OR was 2.63 (95% CI: 1.20–5.78) in the total cohort, and 4.00 (95% CI: 1.39–11.46) in individuals without disability at baseline. Conclusions: The ILSA provides the first data on stroke incidence in Italy on a national basis. Overall, 153,000 new cases can be expected annually in the Italian elderly population. First-ever stroke still has a strong effect on survival and function of older persons.

Selective attention skills in differentiating between Alzheimer's disease and normal aging.

We determined the reliability and validity of a cancellation test of symbols (Symbol Cancellation Test [SCT]), designed to assess visual selective attention deficits in the elderly, on 34 Alzheimer's disease (AD) patients from Bari University Hospital Center, Bari, Italy, and 232 nondemented elderly subjects, aged 68 to 87 years, from the second prevalence survey (1995 through 1996) of the Italian Longitudinal Study on Aging (Casamassima, Bari, Italy). To assess convergent and discriminant validity, the Digit Cancellation Test (DCT), Mini-Mental State Examination (MMSE), and Babcock Story Recall Test (BSRT) were administered. Finally, discriminant accuracy of SCT between AD patients and nondemented elderly subjects was assessed. Inter-rater and test-retest reliability for P1 and P2 was excellent for both AD patients and the normal population, with a high degree of internal consistency. The SCT was significantly correlated with the DCT (0.67), MMSE (0.60), and BSRT (0.33). The classification accuracies of overall performance on the SCT for subjects with and without AD were 0.62 and 0.91, respectively. The SCT is a valid and reliable test to assess selective attention in elderly subjects, in whom dementing illness must be diagnosed and clinically distinct from age-related cognitive decline.

Relation of lipoprotein(a) as coronary risk factor to type 2 diabetes mellitus and low-density lipoprotein cholesterol in patients ≥65 years of age (The Italian Longitudinal Study on Aging)

High levels of serum lipoprotein(a) [Lp(a)] have been associated with increased risk of coronary artery disease (CAD), but this association apparently is not confirmed in elderly people. We evaluated the interactions of Lp(a) with lipid and nonlipid CAD risk factors in a sample of subjects enrolled in the prevalence survey (1992 to 1993) of the Italian Longitudinal Study on Aging (ILSA). The entire population consisted of 5,632 elderly people, aged 65 to 84 years, randomly selected in 8 Italian municipalities. The present cross-sectional study included 400 free-living elderly subjects (74 ± 6 years) from the randomized cohort of Casamassima (Bari, Southern Italy) (n = 704). The results showed that in the elderly population, high serum Lp(a) is a CAD risk factor dependent on type 2 diabetes mellitus and elevated low-density lipoprotein (LDL) cholesterol levels. In particular, the combined effect of high Lp(a) (≥20 mg/dl) and high LDL cholesterol (≥3.63 mmol/L [≥140 mg/dl]), increases coronary risk by 2.75 (95% confidence interval 7.70 to 0.99); finally, the effect of Lp(a) ≥20 mg/dl and LDL cholesterol ≥3.63 mmol/L (≥140 mg/dl), combined with type 2 diabetes mellitus, increases risk of CAD by 6.65 (95% confidence interval 35.40 to 1.25). In the elderly, elevated Lp(a) levels appear not to be an independent predictor of CAD, but this lipoprotein is a risk factor only in subjects with type 2 diabetes mellitus and elevated LDL cholesterol.

PREVALENCE AND RISK FACTORS IN CHRONIC POLYNEUROPATHY IN THE ELDERLY

The elderly are a population at high risk of polyneuropathy because there is a correlation between age and impairment of the peripheral nervous system and because the number of agents that can damage peripheral nerves, including chronic systemic disorders and neurotoxic drugs, increases with age. The Italian Longitudinal Study on Aging (ILSA), a multicenter project designed to study age‐associated diseases, collected data from 8 Italian municipalities. For this study, the definition of peripheral neuropathy by P.J. Dyck (1982) was used. However, only peripheral neuropathies with distal and symmetrical involvement of lower limbs were considered.Diagnosis was articulated in two phases: Phase 1 or screening, administered to all participants. The criteria were: a) self reported diagnosis; b) presence of at least one neurological symptom; and c) presence of at least one positive test at short neurological evaluation. A validation of the screening instruments was performed. Phase 2 or clinical confirmation by a neurologist, based on: a) review of the clinical records; b) a neurological examination; c) a clinical history of the disease; and, d) when available, EMG, blood and spinal fluid examination, and a sural nerve biopsy. Three diagnostic categories were identified: possible, probable and definite DSNLL. The neuropathy was classified as definite only when confirmation by a positive EMG was available. A random sample of 5632 subjects aged 65–84 years was evaluated. A total number of 337 DSNLL were identified (possible, probable, defined). The prevalence is 6.5% (95% C.I. 5.8–7.2) in men and women; the rates by age, geographic area, and clinical severity are described, and the prevalence in the different groups of diabetic patients and non‐diabetic subjects is analyzed. The prevalence obtained in our study is slightly lower than that in a similar recent multicentric study (IGPSG, 1995), but the diagnostic criteria were different. Diabetes is the most common associated disorder with the 20.8% of association, followed by toxic/drug exposure (5% of association).

Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study.

To estimate the incidence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older Italians and evaluate the relationship of age, gender, and education to developing dementia. Cohort incidence study in the context of the Italian Longitudinal Study on Aging. Population sample from eight Italian municipalities. A dementia-free cohort of 3,208 individuals (aged 65-84), individuated after a baseline evaluation performed in 1992 / 93, aimed at detecting prevalent cases. The dementia-free cohort was reexamined in 1995 to identify incident cases. The Mini-Mental State Examination (cutoff 23 / 24) was employed to screen for dementia. Trained neurologists evaluated the individuals who screened positive. Final diagnoses had to meet Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for dementia, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and International Classification of Diseases, Tenth Revision criteria for VaD. Before the follow-up examination, 382 individuals had died (232 had reliable information). Of the 2,826 survivors, 2,266 completed the study. Overall, 127 new dementia cases were identified. Average incidence rates per 1,000 person-years were 12.47 (95% confidence interval (CI)=10.23-14.72) for dementia, 6.55 (95% CI=4.92-8.17) for AD, and 3.30 (95% CI=2.14-4.45) for VaD. Both AD and VaD showed age-dependent patterns. Education was protective against dementia and AD. Women carried a significantly higher risk of developing AD (hazard ratio=1.67, 95% CI=1.02-2.75), and men of developing VaD (hazard ratio=2.23, 95% CI=1.06-4.71). Incidence of dementia in Italy paralleled that in most industrialized countries. About 150,000 new cases per year are expected. A significant gender effect was evidenced for major dementia subtypes. The burden of VaD, especially in men, offers opportunities for prevention.

High plasma insulin and lipids profile in older individuals: the Italian longitudinal study on aging.

The inverse relationship of insulin level to high-density lipoprotein (HDL)-cholesterol and its positive association with hypertriglyceridemia has been demonstrated in several studies; however, the relationship of insulin to low-density lipoprotein (LDL)-cholesterol in elderly persons is not clear. This study investigates the relationships of fasting plasma insulin and selected metabolic and biological risk factors in an aged population. The present study is based on a cross-sectional analysis of the data collected at baseline of the Italian Longitudinal Study on Aging in 1992 on a random sample of 5632 Italians aged 65-84 years. Analyses were performed to compare the distribution of risk factors, such as blood level of lipids, creatinine, albumin, fibrinogen, apolipoprotein A-1 and B, blood pressure, and body mass index (BMI), by quartiles of insulin, in both diabetic and nondiabetic participants. Significantly higher levels of triglycerides and BMI and lower levels of HDL-cholesterol were found in the upper quartile of insulin among nondiabetic individuals. In men, we also found significantly higher levels of systolic and diastolic blood pressure. The same trend for these variables, although not significant for HDL-cholesterol and blood pressure, was seen in diabetic men. In diabetic women, total and LDL-cholesterol were significantly lower in the highest insulin quartile (p <.001), while no significant differences were seen in nondiabetic women or in men. We also found higher levels of white blood cells in the highest insulin quartile of diabetic women. These results, apparently in disagreement with earlier reports on the clustering of cardiovascular disease risk factors in hyperinsulinemic individuals, could be due to the high frequency of chronic inflammation and the high prevalence of urinary infections in older diabetic women.

Lipoprotein(a) serum levels and vascular diseases in an older Caucasian population cohort. Italian Longitudinal Study on Aging (ILSA).

To investigate elevated lipoprotein(a) [Lp(a)] levels as a risk factor for stroke, myocardial infarction, angina, intermittent claudication, and combination of the above in a cohort of unselected older individuals. Population cohort from one of the eight centers participating in the Italian Longitudinal Study on Aging (ILSA). General community. A subsample of 446 subjects (M/F: 231/ 215, mean age: 74.5 +/- 5.7 years) of the original, randomly selected, population cohort of 704 individuals, 65 to 84 years of age, free-living or institutionalized in the Impruneta Municipality, area of Florence, Italy. Conventional vascular risk factors and vascular diseases defined following a two-step procedure (screening phase and confirmation on positives) using standard and validated criteria. Lp(a) levels determined by an ELISA method. No association was observed between elevated Lp(a) levels alone and any of the examined vascular diseases (stroke, myocardial infarction, angina, and intermittent claudication). In contrast, examining the interactions between elevated Lp(a) and conventional vascular risk factors, when elevated Lp(a) was combined with a history of smoking, a marked increase in the risk of vascular diseases combined (odds ratio [OR]: 4.12; 95% confidence interval [CI]: 1.27-13.40) was observed, much higher than that expected based on the additive effect of smoking and elevated Lp(a) alone. With the cautions due to the cross-sectional design of the study and the limited statistical power, these results suggest a possible synergistic effect between elevated Lp(a) levels and other pro-atherogenic factors such as smoking on the risk of vascular diseases in older individuals.

An Innovative Tool for Predicting the Pathologic Stage of Prostate Cancer

Objective: To develop a practical tool for predicting the pathologic stage in prostate cancer. Materials and Methods: Two hundred fifty patients who had had radical prostatectomy were selected from an Italian longitudinal observational study on prostate cancer. Inclusion criteria for selection were the following: a preoperative prostate specific antigen (PSA) value <50 ng/ml; a clinical stage less than or equal to stage T3c (TNM 1992); the availability of the bioptic Gleason score; and the availability of a pathologic specimen obtained during the radical prostatectomy. Pathologic stages were categorized into five levels according to the increasing severity of the illness. Multivariate logistic regression on polythomous ordinal response was performed to obtain a predictive model of disease progression. A set of parallel scale nomographs then was constructed to transfer the predictive model into a new tool, called the “Uro-gramma,” that is able to simplify the practical use of the traditional nomograms. Results: The Gleason score was the factor that influenced the probability of pathologic stage progression the most; PSA and clinical stage were the second and third most significant factors, respectively. Two-way and three-way interactions were tested and were not found to be significant. The confounding effects of age and neoadjuvant hormonal therapy also were tested, and they had no significant influence on the response variable. A logistic regression algorithm then was used to produce a set of nomographs (the Uro-gramma) for the prediction of different pathologic stages using the Gleason score, PSA level, and clinical stage of disease. Conclusion: The predictive model obtained from this Italian study will help physicians and patients in therapeutic decision making. The Uro-gramma provides a new and easier instrument with respect to previous nomograms and multidimensional tables for pathologic stage prediction.

Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging.

To investigate prevalence of "cognitive impairment, no dementia" (CIND) in the Italian older population, evaluating the association with cardiovascular disease and the impact on activities of daily living (ADL). CIND may provide pathogenic clues to dementia and independently affect ADL. Cross-sectional examination in the context of the Italian Longitudinal Study on Aging. Random population sample from eight Italian municipalities. A total of 3,425 individuals aged 65-84 years, residing in the community or institutionalized. Study participants were screened for cognitive impairment by using the Mini-Mental State Examination. Trained neurologists examined those scoring <24. CIND diagnosis relied on clinical and neuropsychological examination, informant interview, and assessment of functional activities. Age-related cognitive decline (ARCD) was diagnosed in CIND cases without neuropsychiatric disorders responsible for the cognitive impairment. Prevalence was 10.7% for CIND and 7.5% for ARCD, increased with age, and was higher in women. Age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06-1.12), stroke (OR, 2.05; 95% CI, 1.26-3.35) and heart failure (OR, 1.73; 95% CI, 1.11-2.68) were significantly and positively associated with CIND at multivariate analysis. Education (OR, 0.61; 95% CI, 0.56-0.65) and smoking (OR, 0.72; 95% CI, 0.54-0.98) showed a negative correlation. Age and myocardial infarction were positively associated with ARCD, whereas a negative correlation was found for education and smoking. The effect of smoking was no more significant either on CIND or ARCD considering current habits or "pack year" exposure. CIND showed an independent impact on ADL (OR, 1.88; 95% CI, 1.41-2.49). CIND is very frequent in older people. The effect of demographic variables and vascular conditions offers opportunities for prevention. The association with functional impairment is useful to evaluate the burden of disability and healthcare demands.

Lipoprotein(A) affects cognitive function in the elderly. The Italian longitudinal study on aging

Lipoprotein(A) affects cognitive function in the elderly. The Italian longitudinal study on aging

Influence of Different Screening Procedures on the Stroke Prevalence Estimates: The Italian Longitudinal Study on Aging

Stroke prevalence surveys are more and more needed for health care and facility planning. Prevalence estimates and costs of the definition procedure may vary depending on different screening strategies. We evaluated the impact of these different strategies on the overall diagnostic procedure and on stroke prevalence estimates in the Italian Longitudinal Study on Aging. A population sample of 5,632 individuals aged 65–84 years was screened for stroke by a simple question on previous stroke diagnosis, questions on possible stroke symptoms and a simple neurological examination. Those screened positive by any of these procedures were fully examined by a neurologist for conclusive diagnosis. We determined the positive predictive value of each procedure on the final stroke diagnosis and calculated prevalence as if each procedure had been used separately. Using the three procedures combined, the prevalence rate was 6.0% (95% confidence interval, 5.4–6.7%). If each procedure had been used as the unique screening tool, the rates would have been 5.1% (4.5–5.7%), 4.1% (3.6–4.7%) and 2.3% (1.9–2.7%), and positive predictive values 66.4, 55.2 and 45.1%, respectively. Different screening procedures can affect stroke prevalence estimates. Compared to more complex screening strategies, the use of a simple question about previous diagnosis as the unique screening tool leads to only a slight underestimation of stroke prevalence and avoids a 66% increase in the number of subjects to be examined in a second-level specialist evaluation, potentially reducing the costs of the overall diagnostic procedure.

Education and the risk of physical disability and mortality among men and women aged 65 to 84: the Italian Longitudinal Study on Aging.

Most studies report that people with higher education enjoy better health and longer life. Although it is well known that most risk factors are more common among individuals with a lower level of education, the underlying mechanism of this association is not fully understood. The objective of this study was to assess the association between education, disability, and mortality. We analyzed data on 1,817 men and 1,643 women, aged 65-84 years, to assess the association of educational level with physical disability and mortality adjusting for age, sex, smoking habit, occupation, and major chronic conditions. The association between educational level and disability was characterized by a dose-response effect, with the relative odds significantly decreased by about 30%, 60%, and 79% in those with 4 or 5, 6 to 8, and more than 8 years of education, compared to those with 3 or less years of education. Death rates were lower among persons with 4 or more years of education compared to those with less education. However, after adjusting for disability status, education was no longer associated with mortality (RR=0.97, CI=0.65-1.43). The strong association of low education with disability found in this study may explain the inverse association with mortality reported in previous studies. Disability, indeed, seems to be the mediator between education and mortality and might be due to the higher severity level of diseases, leading to death, in the lower educated group.

4-07-23 Anticardiolipin antibodies and stroke: Data from the Italian longitudinal study on aging (ILSA)

4-07-23 Anticardiolipin antibodies and stroke: Data from the Italian longitudinal study on aging (ILSA)

Headache in a population-based elderly cohort. An ancillary study to the Italian Longitudinal Study of Aging (ILSA).

The aims of this ancillary study to the Italian Longitudinal Study of Aging were: (1) to provide reliable prevalence data on headache in an elderly population, (2) to classify the subtypes of headache according to International Headache Society criteria, and (3) to identify possible risk factors and associated pathologies in the elderly. A total of 312 subjects were examined, 148 women and 164 men, with a mean age of 73 years (SD 5.5). For 236 subjects (75.7%), 141 men (85.9%) and 95 women (64.2%), headache had never been a problem; 57 subjects (18.3%), 21 men (12.8%) and 36 women (24.3%), reported troublesome headache only in the past. Nineteen subjects (6%), 6 men (3.6%) and 13 women (8.8%), reported current headache: in this group tension-type headache was the most prevalent, accounting for 2.6%; secondary headaches ranked second, accounting for 2.2%; and only 1% had current migraine. Our data indicate female sex and younger age as risk factors for headache, and associate migraine and secondary headaches with hypertension, tension-type headaches and secondary headaches with diabetes, and tension-type headaches with myocardial ischemia.

The Italian Longitudinal Study on Aging (ILSA): Design and methods

The Italian Longitudinal Study on Aging (ILSA) is a population-based, longitudinal study of the health status of Italians aged 65-84 years. The main objectives of ILSA are the study of the prevalence and incidence rates of common chronic conditions in the older population, and the identification of their risk and protective factors. ILSA is also designed to assess age-associated physical and mental functional changes. A random sample of 5632 individuals, stratified by age and gender using the equal allocation strategy, was identified on the demographic lists of the registry office of eight municipalities: Genova, Segrate (Milano), Selvazzano-Rubano (Padova), Impruneta (Firenze), Fermo (Ascoli Piceno), Napoli, Casamassima (Bari), and Catania. An extensive investigation, including interviews, physical exams, and laboratory tests, was conducted at baseline to identify the presence of cardiovascular disease (ischemic heart disease, hypertension, congestive heart failure, arrhythmia, intermittent claudication), diabetes, impaired glucose tolerance, thyroid dysfunction, dementia, parkinsonism, stroke, and peripheral neuropathy, as well as assess physical and mental functional status. The baseline examination was carried out between March 1992 and June 1993; a second comprehensive examination will begin in March 1995. An interim hospital discharge data survey and a mortality survey are currently ongoing to assess the hospitalization rate and the cause-specific mortality rate in this study cohort.