Factors affecting course and survival in Alzheimer's disease. A 9-year longitudinal study.

OBJECTIVE: To evaluate mean survival and to identify prognostic factors in a cohort of patients with Alzheimer's disease (AD). DESIGN: Multicentric 9-year cohort analytic study. SETTING: Seven neurology departments throughout Italy between April 1982 and January 1984. PATIENTS: We recruited a consecutive sample of 145 patients affected by probable AD (Multicenter Italian Study on Dementia protocol, National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). Five were misdiagnosed, and 21 could not participate in the longitudinal study. The clinicodemographic characteristics of the 119 enrolled patients (49 men, 70 women; mean age, 64.7 years; SD, 4.1 years; mean duration of disease, 3.1 years; SD, 1.8 years) did not differ from those of the 26 excluded patients. All underwent extensive cliniconeuropsychological testing every 6 months for at least 2 years until the patient died or our survey ended (April 30, 1991). Mean follow-up was 5.1 years (SD, 2.5 years). MAIN OUTCOME MEASURES: Death, severe functional impairment (a score > or = 17 on the Blessed Dementia Scale), and severe cognitive impairment (a score of < or = 7 on the Information-Memory-Concentration Test). RESULTS: Survival curves obtained by the Kaplan-Meier method indicated that (1) patients with early- and late-onset disease (ie, before or after age 65 years) showed no difference either in relative survival or in time to reach predetermined functional and cognitive end points; (2) severely aphasic patients became profoundly demented significantly sooner than those with mild to moderate aphasia (P < .0001). Among clinicodemographic variables analyzed by a Cox model, severe language disability and functional loss proved to be the best predictors of death independent of age at onset or degree of dementia. CONCLUSIONS: Age at onset did not influence course and survival in AD. Severe aphasia appears to be the best predictor of death and unfavorable course.

Parkinson disease survival: a population-based study.

OBJECTIVE: To evaluate whether the survival of patients with Parkinson disease (PD) is shorter than that of the general population. DESIGN: Survival was investigated in a cohort of patients with PD previously identified during a population-based prevalence study (prevalence day, November 1, 1987, reference follow-up date, October 31, 1995). The survival of patients with PD was compared with that of a control sample randomly selected from the same population (2 controls for each case, matched for age, sex, and study municipality). The causes of death in the 2 groups were also compared. Both univariate and multivariate survival analyses were performed to investigate the association with disease-related variables. SETTING: A door-to-door 2-phase prevalence survey performed in 3 Sicilian municipalities. PATIENTS: Fifty-nine patients with PD and 118 controls. RESULTS: Patients with PD showed a high risk of death (relative risk, 2.3; 95% confidence interval, 1.60-3.39). Greater age at November 1, 1987, high Hoehn-Yahr score, and lack of levodopa therapy were associated with a lower survival on univariate analysis. Multivariate analysis confirmed the association between shorter survival among patients with PD and greater age on November 1, 1987. One-way analysis of variance indicated a different effect of levodopa therapy according to age. Multivariate analysis did not confirm this finding. Pneumonia was the cause of death most frequently associated with PD. CONCLUSION: This study indicates that patients with PD have a shorter survival time than the general population.

Norms for the Mini-Mental State Examination in a healthy population.

BACKGROUND: Although the Mini-Mental State Examination (MMSE) is widely used in clinical practice, few norms exist for healthy populations covering a broad range of ages. OBJECTIVE: To obtain MMSE norms specific for age, gender, and education in healthy adults. METHODS: From the population registers of seven communities across Italy, we selected a proportionate random sample of residents age 20 to 79 years to evaluate their health status with respect to conditions affecting cognitive performance. This sample yielded 908 persons who were deemed to be without cognitive impairment and who were then given the MMSE. We calculated fifth percentile norms and presented them as step functions. We then validated the norms as a screening tool for dementia in persons age 65 to 79 years. The validation was based on unpublished data from a separate study and involved estimates of sensitivity and specificity. RESULTS: The norms declined with advancing age, especially for less educated women. Given any age and sex, the norms were higher for individuals with higher educational levels. In screening for dementia, the norms had a sensitivity of 85% and a specificity of 89%. CONCLUSIONS: When using MMSE scores, it is important to account for age, gender, and education, especially in populations where the educational level is low. Expressing MMSE norms as step functions provides an easy-to-use tool for neurologists and other clinicians.

Dementia is a major predictor of death among the Italian elderly. ILSA Working Group. Italian Longitudinal Study on Aging.

BACKGROUND: Neurologic diseases are rarely listed on death certificates because death is more often attributed to cardiovascular and pneumonic events occurring during terminal stages. OBJECTIVE: To evaluate the effect of major age-associated neurologic and non-neurologic diseases on survival in a cohort of Italian elderly. METHODS: A population-based multicenter survey, carried out in eight Italian municipalities, with a sample of 5,632 individuals aged 65 to 84 years. The entire sample was screened for all the diseases under study, and all individuals were interviewed about risk factors. Those who screened positive underwent clinical assessments by specialists. Two years after the baseline survey, the study population was followed up to determine the vital status either directly from the individuals or from proxy respondents. A copy of the death certificate was obtained for each individual who had died. The risk of dying (mortality risk ratio [MRR]) was calculated using the Cox proportional hazards model in which we included all the diseases under study, age, gender, and years of education. RESULTS: At follow-up (mean duration 26.7 +/- 5.4 months) 444 individuals had died. The Cox proportional hazards model selected the following as significant predictors of death: age (for year of age MRR = 1.12; 95% confidence interval [CI], 1.08 to 1.15), male gender (MRR = 1.72; 95% CI, 1.27 to 2.34), institutionalization (MRR = 4.17; 95% CI, 2.20 to 7.94), dementia (MRR = 3.61; 95% CI, 2.55 to 5.11), neoplasm (MRR = 2.01; 95% CI, 1.20 to 3.38), heart failure (MRR = 1.87; 95% CI, 1.27 to 2.76), and diabetes (MRR = 1.62; 95% CI, 1.12 to 2.34). CONCLUSIONS: These data provide further evidence on the malignancy of dementia, which proved the major predictor of death in the elderly, with an MRR higher than neoplastic diseases and other severe age-associated conditions.

Prevalence of diabetic neuropathy with somatic symptoms: a door-to-door survey in two Sicilian municipalities. Sicilian Neuro-Epidemiologic Study (SNES) Group.

In a door-to-door survey conducted in two municipalities of Sicily, we ascertained the prevalence of diabetic neuropathy. Our case-finding was restricted to subjects with somatic symptoms. During phase 1, we administered a screening instrument for peripheral neuropathy to 14,540 persons residing in Santa Teresa di Riva (Messina Province) and Terrasini (Palermo Province). During phase 2, neurologists evaluated those subjects who had screened positive. Diagnoses were based on clinical criteria only, and were reviewed by an adjudication panel. We found 39 persons (27 women, 12 men) affected by diabetic neuropathy. The crude prevalence, as of November 1, 1987, was 268.2 cases per 100,000 population. The prevalence increased with advancing age for both sexes and was consistently higher in women. The most common type was distal symmetric polyneuropathy. The median time between diagnosis of diabetes mellitus and onset of diabetic neuropathy was 8 years, and almost all identified persons with diabetic neuropathy were under treatment for diabetes mellitus.

Prevalence of essential tremor: a door-to-door survey in Terrasini, Sicily. Sicilian Neuro-Epidemiologic Study Group.

As part of a door-to-door neuroepidemiologic survey, we investigated the frequency and distribution of essential tremor (ET) in a Sicilian municipality. During phase 1, we administered a screening instrument for tremor to 7,653 persons residing in Terrasini (Palermo province). During phase 2, neurologists evaluated those subjects who had screened positive. The diagnoses, based on specified clinical criteria, were reviewed to increase reliability across neurologists. We found 31 subjects affected by ET (17 men, 14 women); 11 patients (35.5%) reported a familial aggregation. The prevalence of ET as of November 1, 1987, was 405.1 per 100,000 for the total population, and 1,074.9 per 100,000 for those 40 years old or older. The prevalence increased with advancing age for both sexes and was slightly but consistently higher in men. Comparison with other studies suggests striking geographic variation, which may reflect genetic differences.

Prevalence of Parkinson's disease and other types of parkinsonism: a door-to-door survey in three Sicilian municipalities. The Sicilian Neuro-Epidemiologic Study (SNES) Group.

We investigated the prevalence of Parkinson's disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinson's disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinson's disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinson's disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment.

Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging.

OBJECTIVE: To study the association of estrogen-replacement therapy and other estrogen-related variables with Alzheimer's disease in postmenopausal women. BACKGROUND: Postmenopausal estrogen use has been reported to lower the risk of Alzheimer's disease. DESIGN: A population-based, multicenter survey was carried out in eight Italian municipalities. The sample of 2,816 women, aged 65 to 84 years, was randomly selected from the population register of each municipality and stratified in 5-year age groups. All women were screened using the Mini-Mental State Examination and interviewed concerning risk factors. Those who screened positive underwent a clinical assessment. Dementia syndrome was diagnosed according to DSM-III-R criteria, and Alzheimer's disease was diagnosed according to NINCDS-ADRDA criteria for possible and probable Alzheimer's disease. RESULTS: The estimated prevalence of postmenopausal estrogen use adjusted to the 1991 Italian female population was 12.3%. The frequency of estrogen use was higher among nonpatients compared with Alzheimer's disease patients (odds ratio, 0.24; 95% confidence interval, 0.07 to 0.77). The inverse association between estrogen therapy and Alzheimer's disease remained significant after adjustment for age, education, age at menarche, age at menopause, smoking and alcohol habits, body weight at the age of 50 years, and number of children (odds ratio, 0.28; 95% confidence interval, 0.08 to 0.98). CONCLUSIONS: Our data from a population-based study support the hypothesis that estrogen-replacement therapy is associated with a reduced prevalence of Alzheimer's disease in postmenopausal women. Prospective clinical trials are required to enable women and their physicians to weigh risks and benefits of estrogen-replacement therapy for the prevention of dementia.

Parkinson's disease and parkinsonism in a longitudinal study: two-fold higher incidence in men. ILSA Working Group. Italian Longitudinal Study on Aging.

OBJECTIVE: To determine the incidence of parkinsonism and PD in the Italian elderly, and to explore the relation with age and gender. METHODS: In eight Italian municipalities, a population-based, parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were directly contacted (screening and clinical examination). Cohort members who had died were studied using death certificates, clinical records, and information gathered from relatives and general practitioners. Parkinsonism diagnosis and subtyping were made according to specified diagnostic criteria. RESULTS: The cohort consisted of 4,341 individuals (65 to 84 years of age): 596 died before the examination, 2,863 (76.4% of the survivors) completed the screening procedure, and 882 refused to participate. The authors found 68 incident cases of parkinsonism: 42 PD (62%), 7 drug-induced parkinsonism (10%), 8 parkinsonism in dementia (12%), 8 vascular parkinsonism (12%), and 3 parkinsonism, unspecified (5.8%). Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 84 years, adjusted to the 1992 Italian population, was 529.7 (95% CI, 400.5 to 658.9) for parkinsonism, and 326.3 (95% CI, 224.1 to 427.5) for PD. Incidence rates for both parkinsonism and PD increased with age in both men and women; men had higher rates in every age group. Age-adjusted relative risk in men compared with women was 1.66 (95% CI, 1.02 to 2.70) for parkinsonism and 2.13 (95% CI, 1.11 to 4.11) for PD. CONCLUSIONS: Incidence of parkinsonism and PD increased with age, PD was the most common type of parkinsonism, and men had a risk of developing PD twice that of women.

Familial aggregation of Parkinson's disease: a population-based case-control study in Europe. EUROPARKINSON Study Group.

OBJECTIVE: To investigate the familial aggregation of PD in a large collaborative population-based case-control study. BACKGROUND: Most previous case-control studies of the familial aggregation of PD have been hospital- or clinic-based. METHODS: We included 219 prevalent cases ascertained in three European populations (centers), using a two-phase design consisting of screening and examination by a neurologist. Each case was matched by age, sex, and center to three controls drawn from the same populations (n = 657). Presence of PD among first-degree relatives (parents and siblings) was determined using the family history approach for 175 cases and 481 controls. RESULTS: Overall, a positive family history (at least one parent or sibling affected by PD) was reported in 10.3% of patients and 3.5% of controls (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.6 to 6.6). A similar association was observed when analyses were restricted to nondemented patients and controls (OR = 3.9; 95% CI = 1.7 to 8.7) or to newly diagnosed patients (OR = 3.3; 95% CI = 0.9 to 11.9). We found a significant trend of increasing risk with increasing number of affected relatives (p = 0.003). Analyses stratified by age showed a stronger association for younger PD patients (OR = 7.6; 95% CI = 1.5 to 38.9) than for older patients (OR = 2.5; 95% CI = 1.1 to 5.7). CONCLUSIONS: In this large sample of prevalent PD patients and population-matched controls, PD significantly aggregates in families, with the strength of the association being age-dependent. Therefore, familial factors, which can be genetic, environmental, or both, play a role in PD.

Validating screening instruments for neuroepidemiologic surveys: experience in Sicily. Sicilian Neuro-Epidemiologic Study (SNES) Group.

In a hospital setting in Sicily, we assessed a screening instrument developed for a prevalence survey of parkinsonism, peripheral neuropathies, stroke, and epilepsy. The subjects consisted of (1) hospital patients with any of the above-mentioned diseases, to investigate sensitivity; and (2) hospital visitors free of all these diseases, to investigate specificity. The standard for comparison was a clinical evaluation based on specified criteria. Trained interviewers administered the screening instrument, asking subjects to answer symptom questions and to perform simple physical tasks. For the questions and tasks together, the sensitivity estimates were 100% for parkinsonism (n = 21), 96% for peripheral neuropathies (n = 22), 96% for stroke (n = 22), and 96% for epilepsy (n = 22), while the specificity estimate was 86% (n = 21). Analogous estimates were computed for the set of questions, for the set of tasks, and for each question and task individually. Despite limitations in our approach, we concluded that the screening instrument would be adequate for its intended use.

Sleep complaints in community-dwelling older persons: prevalence, associated factors, and reported causes.

OBJECTIVES: To determine the prevalence rates of self-reported sleep complaints and their association with health-related factors. DESIGN: A cross-sectional study. SETTING: People living in the community. PARTICIPANTS: A total of 2398 noninstitutionalized individuals, aged 65 years and older, residing in the Veneto region, northeast Italy. MEASUREMENTS: Odds ratios for the association of sleep complaints with potential risk factors. RESULTS: The prevalence of insomnia was 36% in men and 54% in women, with increased risks for women (odds ratio (OR) = 1.69, 95% CI: 1.3-2.1), depression (OR = 1.93, 95% CI, 1.5-2.5), and regular users of sleep medications (OR = 5.58, 95% CI, 4.3-7.3). About 26% of men and 21% of women reported no sleep complaints. Night awakening, reported by about two-thirds of the participants, was the most common sleep disturbance. Women and regular users of sleep medications had significantly increased odds for insomnia and for not feeling rested upon awakening in the morning. Depressive symptomatology was more strongly associated with insomnia and night awakening than with awakening not rested, whereas physical disability was more strongly associated with awakening not rested than with the other two sleep disturbances. CONCLUSION: Our findings show that sleep complaints, highly common among older Italians, are associated with a wide range of medical conditions and with the use of sleep medications. Further longitudinal studies are needed to investigate the causes and the negative health consequences of sleep disturbances to improve both the diagnosis and treatment.

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

OBJECTIVES: 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. DESIGN: Cross-sectional examination in the context of the Italian Longitudinal Study on Aging. SETTING: Random population sample from eight Italian municipalities. PARTICIPANTS: A total of 3,425 individuals aged 65-84 years, residing in the community or institutionalized. MEASUREMENTS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Prevalence survey of major neurological disorders in Sicily. Results of a pilot study.

A pilot study on the prevalence of neurological disorders in Sicily was carried out with a protocol never previously used in Italy. A screening questionnaire was administered to 1,601 subjects of a community, designed to identify patients with cerebrovascular diseases, epilepsy, extrapyramidal syndromes, peripheral neuropathies, migraine and intracranial neoplasms. Of 262 subjects who were identified as likely to be suffering from neurological illness, 248 (94.6%) were examined by a neurologist. Of these, 8.9% were found to be normal, 46.8% were suffering from non-neurological diseases, 44.3% had one or more neurological diseases (prevalence of 6.8%). This pilot study proved to be a good starting-point for a future major survey.

Parkinson's disease, smoking, and family history. EUROPARKINSON Study Group.

There is growing evidence that both genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). The hypothesis of an interaction between genetic and environmental risk factors has been little explored, and never using a population-based case-control study design. Our objective was to investigate the possible interaction between smoking and family history in the etiology of PD, as part of a collaborative population-based case-control study. We included 149 nondemented PD patients ascertained in three European prevalence surveys using a two-phase design. Each patient was matched by age (+/-2 years), gender, and center to three controls drawn from the same populations (n=375). Presence of PD among first-degree relatives and smoking history were assessed through an interview for 127 cases and 306 controls. In the overall sample we found suggestive evidence that family history and ever-smoking interact in determining the risk of PD (P=0.09), with individuals exposed to both risk factors having the highest risk (OR=10.0; 95% CI=2.0-49.6). Analyses were repeated after stratification into two age-groups (cutoff: 75 years). In older patients, the joint exposure to both risk factors was associated with a significant increase in the risk of PD (OR=17.6; 95% CI=1.9-160.5). Among younger subjects, the OR for joint exposure was not significant. In conclusion, our findings suggest that smoking and family history interact synergistically on a multiplicative scale in determining the risk of PD in individuals older than 75 years.

Some relevant aspects in conducting cataract prevalence studies.

This paper deals with some crucial issues relevant to cataract prevalence studies. The desirable property of comparability for different studies is illustrated and it is brought to light that prevalence studies can be planned in order to find out possible risk factors when designed in accordance with some criteria.

Prognosis of severe attacks in ulcerative colitis: effect of intensive medical treatment.

BACKGROUND: Severe attacks of ulcerative colitis have a high risk of colectomy. AIMS: To evaluate the effects of standard medical management and to identify the clinical and laboratory variables capable of predicting the clinical outcome. MATERIALS AND METHODS: Prospective study monitoring the clinical and laboratory variables in 67 patients with severe colitis. Therapy consisted of prednisone, cyclosporin if no response, and azathioprine for maintenance. End-points were colectomy or remission. Logistic regression analysis was applied for statistical evaluation. RESULTS: Fourteen (20%) patients required colectomy, 34 (50%) patients achieved remission with steroids, 25 (37%) patients received cyclosporin, 19 (76%) with benefit. Increased body temperature, pulse rate, sedimentation rate and C-reactive protein levels on admission were significantly associated with colectomy. Sedimentation rate greater than 75 mm/h and body temperature exceeding 38 degrees C at admission had 4.6- and 8.8-fold increased risk of colectomy. Less than 40% reduction in the bowel movements within 5 days predicted no response to steroids. Azathioprine maintained remission in 70% of the patients. CONCLUSIONS: Elevated sedimentation rate and fever at day 1 best predict colectomy in severe colitis. Less than 40% reduction in the bowel movements at day 5 predicts no response to steroids. Cyclosporin has a high rate of success in acute attacks and azathioprine in maintaining remission.

LEIPAD, an internationally applicable instrument to assess quality of life in the elderly.

A questionnaire to assess quality of life in the elderly was developed under the auspices of the European office of the World Health Organization. Stages in construction of the instrument, which was designed for international application, particularly at the primary level, are described. The latest version of the questionnaire is composed of 49 self-assessment item, 31 of which can be grouped into 7 subscales: Physical Function, Self-Care, Depression and Anxiety, Cognitive Functioning, Sexual Functioning, and Life Satisfaction. The remaining 18 items serve as moderators for assessing the influence of social desirability factors and personality characteristics on the individual scores for the 7 core instrument subscales. The questionnaire has been administered to 586 individuals aged 65 years and over recruited in communities in Italy (Padua and Brescia), the Netherlands (Leiden), and Finland (Helsinki). The main psychometric characteristics of the instrument, together with its concurrent validity with the Rotterdam Questionnaire, are illustrated.