Alewijn Ott

Diabetes mellitus and the risk of dementia The Rotterdam Study

Objective: To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD. Background: Both dementia and diabetes are frequent disorders in elderly people. Methods: Prospective population-based cohort study among 6,370 elderly subjects. At baseline study participants were examined for presence of diabetes mellitus. Nondemented participants were followed up, on average, for 2.1 years. Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup. To complete the follow-up, medical files were studied of persons who could not be reexamined. We estimated relative risks with proportional hazard regression, adjusting for age, sex, and possible confounders. Results: During the follow-up, 126 patients became demented, of whom 89 had AD. Diabetes mellitus almost doubled the risk of dementia (relative risk [RR] 1.9 [1.3 to 2.8]) and AD (RR 1.9 [1.2 to 3.1]). Patients treated with insulin were at highest risk of dementia (RR 4.3 [1.7 to 10.5]). Conclusion: The diabetes attributable risk for dementia of 8.8% suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients.

Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study

BACKGROUND Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimers disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimers disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimers disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E. METHODS We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimers disease, and 1698 individuals who were not demented. Indicators of atherosclerosis included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography, and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis) to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms were assessed in 246 patients and in 928 controls. FINDINGS All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimers disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimers disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimers disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimers disease was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001). INTERPRETATION These findings suggest that dementia and its two major subtypes Alzheimers disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimers disease.

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study

Abstract Objective: To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. Design: Population based cross sectional study. Setting: Ommoord, a suburb of Rotterdam. Subjects: 7528 participants of the Rotterdam study aged 55-106 years. Results: 474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimers disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinsons disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. Conclusions: The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimers disease. In this study an inverse dose-response relation was found between education and dementia—in particular, Alzheimers disease. Key messages Key messages Of all cases of dementia, 72% were cases of Alzheimers disease The pronounced increase in prevalence of dementia with age was due to a substantial increase in Alzheimers disease Alzheimers disease was more often diagnosed in less educated people The association between dementia and education could not be explained by cardiovascular disease comorbidity

Rates and risk factors for dementia and Alzheimer’s disease Results from EURODEM pooled analyses

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 Disrders, 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.

Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers.

Staphylococcus aureus is the second most frequent cause of nosocomial blood infections. We screened 14008 non-bacteraemic, non-surgical patients for S aureus nasal carriage at admission, and monitored them for development of bacteraemia. Nosocomial S aureus bacteraemia was three times more frequent in S aureus carriers (40/3420, 1.2%) than in non-carriers (41/10588, 0.4%; relative risk 3.0, 95% CI 2.0-4.7). However, in bacteraemic patients, all-cause mortality was significantly higher in non-carriers (19/41, 46%) than in carriers (seven/40, 18%, p=0.005). Additionally, S aureus bacteraemia-related death was significantly higher in non-carriers than in carriers (13/41 [32%] vs three/40 [8%], p=0.006). S aureus nasal carriers and non-carriers differ significantly in risk and outcome of nosocomial S aureus bacteraemia. Genotyping revealed that 80% of strains causing bacteraemia in carriers were endogenous.

Atrial Fibrillation and Dementia in a Population-Based Study: The Rotterdam Study

BACKGROUND AND PURPOSE Atrial fibrillation is a frequent disorder in the elderly and a known risk factor for cerebrovascular stroke. We investigated the association of atrial fibrillation with dementia and cognitive impairment in a large cross-sectional, population-based study in the elderly. METHODS Of the 6584 participants in the Rotterdam Study aged 55 to 106 years, detailed information on dementia status and ECG abnormalities was available. Dementia was diagnosed in three phases. First, participants were screened. Screen-positive subjects were tested further. Those with possible dementia underwent an extensive diagnostic workup. Dementia and dementia subtypes were diagnosed according to prevailing criteria. Cognitive impairment was defined as a Mini-Mental State Examination test score of < 26 points for a nondemented subject. RESULTS Atrial fibrillation was diagnosed in 195, dementia in 276, and cognitive impairment in 635 subjects. We found significant positive associations of atrial fibrillation with both dementia and impaired cognitive function (age- and sex-adjusted odds ratios, 2.3 [95% confidence interval, 1.4 to 3.7] and 1.7 [95% confidence interval, 1.2 to 2.5]), respectively). The strongest association was found not for vascular dementia but rather for Alzheimers disease with cerebrovascular disease. The associations were stronger in women, and the relation with dementia was more pronounced in the relatively younger elderly. A history of stroke in subjects with atrial fibrillation could not account for these associations. CONCLUSIONS Dementia and subtypes Alzheimers disease and vascular dementia may be related to atrial fibrillation even if no clinical stokes have occurred.

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies

Objective: To study the difference in risk for dementing diseases between men and women. Background: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. Methods: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. Results: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). Conclusion: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.

Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study

BACKGROUND Previous studies suggested a protective effect of smoking on Alzheimers disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. METHODS We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimers disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimers disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimers disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimers disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). INTERPRETATION Smoking was associated with a doubling of the risk of dementia and Alzheimers disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimers disease.

Prevalence of Parkinson's disease in the elderly The Rotterdam Study

We assessed the prevalence of Parkinsons disease (PD) in a general elderly population in the Netherlands.The study formed part of the Rotterdam Study, a population-based door-to-door study, and included 6,969 persons 55 years of age or older living in a suburb of Rotterdam, the Netherlands. All participants were examined, and those who either had at least one possible cardinal sign of parkinsonism at the neurologic screening, reported that they had PD, or were taking antiparkinsonian drugs were invited for further evaluation. The prevalence of PD in this population was 1.4% (1.2% for men, 1.5% for women). Prevalence increased with age, and prevalence figures were 0.3% for those aged 55 to 64 years, 1.0% for those 65 to 74, 3.1% for those 75 to 84, and 4.3% for those 85 to 94. The corresponding age-specific figures for men were 0.4%, 1.2%, 2.7%, and 3.0%, and for women, 0.2%, 0.8%, 3.4%, and 4.8%. Among 95- to 99-year-old women the prevalence was 5.0%. Twelve percent of the subjects with PD were detected through the screening and had not been diagnosed previously. NEUROLOGY 1995;45: 2143-2146

Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam Study

Based on reports that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimers disease (AD), we studied the cross-sectional relation between NSAID use and the risk for AD in a population-based study of disease and disability in older people. After controlling for age, education, gender, and use of benzodiazepines, we found a relative risk (RR) for AD of 0.38 (0.15 to 0.95) when comparing NSAID users (n equals 365) to NSAID non-users (n equals 5,893). To address confounding by indication or contraindication, we compared NSAID users with a subset of NSAID non-users who were using topical medication for ear, eye, or dermatologic conditions (n equals 365). In this comparison, the adjusted RR for AD was 0.54 (0.16 to 1.78). These findings are compatible with a possible protective effect of NSAIDs on the risk for AD.