Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia.

OBJECTIVE: To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma. BACKGROUND: These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled. METHODS: The authors performed a pooled analysis of four European population-based prospective studies of individuals 65 years and older, with 528 incident dementia patients and 28,768 person-years of follow-up. Patients were detected by screening the total cohort with brief cognitive tests, followed by a diagnostic assessment of those who failed the screening tests. Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (revised), and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Incident rates and relative risk (95% CI) express the association of a risk factor for dementia. RESULTS: Incident rates for dementia and AD were similar across studies. The incidence of AD increased with age. At 90 years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000 person-years. Female gender, current smoking (more strongly in men), and low levels of education (more strongly in women) increased the risk of AD significantly. A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly. CONCLUSION: Contrary to previous reports, head trauma was not a risk factor for AD, and smoking did not protect against AD. The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies. Female gender may modify the risk of AD, whether it be via biological or behavioral factors.

Incidence and risk factors of ischaemic and haemorrhagic stroke in Europe. EUROSTROKE: A collaborative study among research centres in Europe: rationale and design.

EUROSTROKE is a collaborative study among ten European research centres to investigate (1) the variation in incidence of fatal and non-fatal ischaemic and haemorrhagic stroke among populations in different European countries; (2) whether the observed differences in stroke incidence across countries can be explained by differences in prevalence of established cardiovascular risk factors; (3) the relative importance of selected dietary factors (potassium intake, smoking, alcohol consumption), haemostatic disturbances (fibrinogen) and co-morbidity (rheumatic heart disease, atrial fibrillation) compared to established risk factors as determinants of the occurrence of ischaemic and haemorrhagic stroke. The EUROSTROKE database is drawn from ten European population-based prospective follow-up studies (cohorts) and is designed as a case-control study nested within these ten ongoing studies.

Raven's colored progressive matrices: a normative study of a random sample of healthy adults.

Raven's Colored Progressive Matrices Test (RCPM) was administered to 894 normal healthy adults who were randomly selected in six Italian cities and in the Republic of San Marino. Gender, age, and education significantly influenced overall test performance, and performance on different RCPM subsets. Findings from this large random sample provide demographic corrections to test scores for use in clinical practice.

Origin of the distinction between Alzheimer's disease and senile dementia: how history can clarify nosology.

Since the beginning of the century, psychiatrists and neurologists have been arguing about the identity of presenile (Alzheimer's disease) and senile dementia. History reveals that the distinction was originally based on anecdotal clinical observations and that competition among universities was one of the underlying determinants. The personal opinion of Kraepelin played a major role. Given his widespread reputation and authority, he generated a dogma difficult to change. Reports based on large clinicopathologic series have shown that the pathologies of presenile and senile dementia are not qualitatively different. Although the controversy continues, many have come to regard Alzheimer's disease and senile dementia as part of the same spectrum of disease, independent of the age of onset.

Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population.

We conducted a case-control study of 116 patients with the clinical diagnosis of Alzheimer's disease (AD) in seven Italian centers. One hundred sixteen hospital controls and 97 population controls were matched by age, sex, and region of residence to the cases. A structured questionnaire was administered to the next-of-kin of cases and controls by trained interviewers to identify possible risk factors. Genetic, viral, toxic, immunologic, medical, surgical, and personality factors were investigated. Dementia among first- or second-degree relatives and advanced age of the mother at subject's birth (age over 40) were associated with AD. Head trauma was more frequent in cases than in either hospital or population controls, but the differences were not significant. Our data did not confirm the previously reported association with antecedent thyroid disease or family history of Down's syndrome.

Epidemiology of clinically diagnosed Alzheimer's disease.

This report reviews the current status of descriptive and analytic epidemiology of clinically diagnosed Alzheimer's disease (AD). Since AD can be diagnosed with certainty only at autopsy, currently available epidemiological data are based on a presumed clinical diagnosis. Current data indicate that AD represents a major health problem, at least in the developed countries. The prevalence ratio for AD ranges between 1.9 and 5.8 cases per 100 population aged 65 and over. Moreover, its prevalence is likely to increase in the next twenty years as a consequence of current demographic trends. The prevalence ratio for AD increases steeply with age and is higher in females. Incidence rates show a similar pattern, suggesting that AD should not be subdivided in a presenile and a senile form based on age of onset alone. Annual incidence rates of 2.4 cases per 100,000 population between ages 40 and 60, and 127 cases per 100,000 population after age 60 have been reported. Several case-control studies show that the occurrence of either dementia or Down's syndrome in other family members, advanced age of the mother at subject's birth, and head injury are possible risk factors.

Observations on the effects of protease inhibitors on the suppression of experimental allergic encephalomyelitis.

Inhibitors of proteolytic enzymes were tested for their ability to suppress the clinical signs and CNS lesions produced by injection of purified myelin in complete Freund's adjuvant into Lewis rats. Pepstatin or a series of neutral protease inhibitors including aprotinin, soybean trypsin inhibitor, leupeptin, antipain, trans-aminomethyl cyclohexane carboxylic acid (AMCA), epsilon-amino caproic acid (EACA) nitrophenyl guanidino benzoate (NPGB), D- and L-polylysine, or a new commercial protease inhibitor, dipropionyl Rhein (DPR) were injected daily beginning on day 7 after immunization of rats with myelin. Aprotinin and soybean trypsin inhibitor exacerbated the symptoms and lesions of experimental allergic encephalomyelitis (EAE), leupeptin and antipain had no effect, and the plasminogen activators AMCA, EACA, NPGB, as well as poly-L- and poly-D-lysine and DPR suppressed various aspects of EAE. The measurement of acid protease as a biochemical method for quantitation of the degree of cellular infiltration into the CNS is proposed, and the results with the various treatments presented. AMCA and NPGB may exert their effects at the site of entrance of the lymphoid cells into the CNS.