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M M Breteler

Publications and source records attributed to M M Breteler.

At least 19 recordsLinked to original sources
PubMed2001

Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease.

BACKGROUND: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. METHODS: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. RESULTS: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. CONCLUSIONS: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.

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PubMed2001

Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study.

OBJECTIVE: To determine the relationship between cerebral white matter lesions (WML) and subjective cognitive dysfunction. BACKGROUND: Subjective cognitive dysfunction is present when a person perceives failures of cognitive function. When annoying enough, these failures will be expressed as complaints. Subjective cognitive dysfunction may be a prelude to or coincide with objective cognitive impairment. WML have been related to objective cognitive impairment and dementia, but their relationship with subjective cognitive dysfunction is not clear. Previous population-based studies on the latter relationship have been limited in sample size, recording of subjective cognitive function, and assessment of WML severity. METHODS: We randomly sampled 1,049 elderly nondemented participants from the general population. Data on subjective cognitive dysfunction and its progression were derived from a 15-item questionnaire. Objective cognitive performance was assessed using a series of neuropsychological tests. WML were scored on MRI for periventricular and subcortical regions separately. RESULTS: WML were associated with more subjective cognitive failures. WML were more severe for participants reporting progression of these failures compared with participants without these failures, especially within participants with better than average cognitive performance (p = 0.008, for periventricular WML). Participants with severe WML reported progression of cognitive failures more than twice as often than did those with little or no WML. The relationship between the severity of WML and subjective cognitive failures was present for periventricular and subcortical WML. CONCLUSIONS: WML are associated with subjective cognitive failures and in particular with reporting progression of these failures, even in the absence of objective cognitive impairment.

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PubMed2001

Reproductive period and risk of dementia in postmenopausal women.

CONTEXT: Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied. OBJECTIVE: To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause. DESIGN AND SETTING: The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands. PARTICIPANTS: A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia. MAIN OUTCOME MEASURES: Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause. RESULTS: During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed. CONCLUSION: Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.

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PubMed2001

Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects.

A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the present study, haplotype analysis, using 10 microsatellite markers covering a 4.7-cM region known to contain the parkin gene, was performed in 48 families, mostly from European countries, with early-onset autosomal recessive parkinsonism. The patients carried 14 distinct mutations in the parkin gene, and each mutation was detected in more than one family. Our results support the hypothesis that exon rearrangements occurred independently, whereas some point mutations, found in families from different geographic origins, may have been transmitted by a common founder.

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PubMed2001

CYP2D6 polymorphism in Parkinson's disease: the Rotterdam Study.

The CYP2D6 polymorphism has been studied extensively in association with Parkinson's disease (PD), with no consistent results. Several explanations, such as differences in study design or bias in the selection of the control population, have been offered for these inconsistent results. We designed a case control study nested within a prospective population-based cohort study in which cases and controls were sampled from the same source population. To assess the significance of the CYP2D6 gene in PD, we investigated two mutant alleles, CYP2D6*3 and CYP2D6*4, associated with poor metabolism and the wild type allele in 80 patients with PD and 156 matched controls, frequency matched on age and gender. No differences between cases and controls were found for the poor metabolizer genotype. However, we found that in contrast to earlier reports, the CYP2D6*4 mutant allele frequency was lower in cases as compared to controls, albeit not statistically significant. Our result supports the hypothesis that the CYP2D6 gene is not a major gene responsible for PD.

Adult↗
PubMed2001

MR spectroscopy detection of lactate and lipid signals in the brains of healthy elderly people.

Magnetic resonance spectroscopy was used to assess the presence of brain lactate and lipid signals, frequently associated with the presence of pathology, in healthy persons of 60-90 years old (n = 540). Lactate and lipid signals were observed in, respectively, 25 and 6% of women, and 18 and 2% of men. Upon adjustment for age, and for MRI-detected cerebral atrophy and white matter lesions, the gender differences in lactate and lipid remained the same (p = 0.05 and p = 0.03, respectively). Brain lactate and lipid signals appear to be intrinsic to aging. However, the presence of these metabolites in very focal areas only, rather than in any distributed fashion within the brain (the latter generally the case with cerebral atrophy and white matter lesions), strongly suggests the existence of asymptomatic focal pathology not shown on MRI.

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PubMed2001

Variable expression of presenilin 1 is not a major determinant of risk for late-onset Alzheimer's disease.

We have previously reported a significant association between early-onset Alzheimer's disease (EOAD) and an allele in the promoter of presenilin 1 (PSEN1) significantly decreasing PSEN1 expression in vitro. For late-onset Alzheimer's disease (LOAD), numerous studies have reported inconsistent associations with a PSEN1 intronic polymorphism. We therefore hypothesized that linkage disequilibrium between the intronic PSEN1 polymorphism and the functional promoter polymorphism might explain the conflicting reports in LOAD. We analysed both variations in 356 LOAD patients and 230 controls in a population-based case-control study. In addition, we re-analysed all published literature on the PSEN1 intronic polymorphism in a meta-analysis. No significant association was found with the PSEN1 intronic or promoter polymorphism in our case-control sample. In the meta-analysis no major differences between patients and controls were found for the PSEN1 intronic variation. Together, our results do not support a major role for variable expression of PSEN1 in LOAD.

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PubMed2001

The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. This is the most frequent form of monogenic parkinsonism so far identified. The associated phenotypical spectrum encompasses early onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with the earliest onset, and with clinically typical Parkinson's disease in cases with later onset. Despite clinical features, Lewy bodies are not found at autopsy in brains of patients with parkin mutations. The parkin protein possesses ubiquitin ligase activity, which is abolished by the pathogenic mutations.

Age of Onset↗
PubMed2001

Evaluation of antiparkinsonian drugs in pharmacy records as a marker for Parkinson's disease.

AIM: The aim of this study was to determine whether use of antiparkinsonian drugs in pharmacy records can be used as a marker for patients with Parkinson's disease (PD). METHOD: Data were obtained from the Rotterdam Study, a community-based prospective cohort study among people aged 55 years or older who were all screened for PD. For 5510 persons, of whom 74 had PD, pharmacy records were available. Stepwise logistic regression analysis was used to evaluate whether age, sex and use of the antiparkinsonian drugs amantadine, anticholinergics, dopamine agonists, levodopa and selegiline, were predictive variables for PD. For each individual a probability for having PD was calculated. Sensitivity, specificity and positive predictive value (PPV) were calculated at different cut-off values based on calculated probabilities. RESULTS: More than 90% of the users of levodopa, bromocriptine, selegiline, and users of at least two different antiparkinsonian drugs had PD. Age, use of amantadine, anticholinergics, bromocriptine, levodopa, and selegiline were predictive variables for PD. After application of different cut-off values, sensitivity was at most 66.2%, and specificity was at least 99.8%. A PPV of higher than 90% was obtained at higher probabilities. CONCLUSION: Based on the high PPV of our predictive model, antiparkinsonian drugs can be used as a reliable marker for PD in pharmacy records. Because sensitivity is low, pharmacy records cannot be used to estimate prevalence of PD.

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PubMed2001

Serum carotenoids and cerebral white matter lesions: the Rotterdam scan study.

OBJECTIVES: To study the relation between serum levels of carotenoids and white matter lesions (WMLs) on magnetic resonance imaging (MRI). DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Rotterdam Scan Study. PARTICIPANTS: Two hundred and three nondemented older persons, age 60 to 90, from the Rotterdam Scan Study. MEASUREMENTS: Serum levels of carotenoids were determined. WMLs on MRIs were rated separately into periventricular and subcortical WMLs. Odds ratios (ORs) for the presence of severe WMLs (upper decile) were calculated per standard deviation (SD) increase in serum carotenoid level and per SD increase in overall carotenoid serum level. Effect modification by smoking status was studied through stratified analyses. RESULTS: Increasing levels of all the separate carotenoids were associated with less severe periventricular WMLs, which reached statistical significance for the overall carotenoid serum level (OR 0.4 per SD; 95% confidence interval (CI) = 0.2-0.9). We found no association between carotenoid levels and the presence of severe subcortical WMLs (OR 1.2 per SD; 95% CI = 0.7-2.0). The association of carotenoid levels with severe periventricular WMLs was more marked in those who ever smoked (OR 0.1 per SD; 95% CI = 0.0-0.9) than in those who had never smoked (OR 0.9 per SD; 95% CI = 0.4-2.1). CONCLUSIONS: These findings are compatible with the view that high levels of carotenoids may protect against WMLs in the periventricular region, in particular in smokers. Longitudinal studies with repeated measurements of both carotenoids and WMLs are necessary to explore this hypothesis further.

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PubMed2001

Is drug treatment of hypertension in clinical practice as effective as in randomized controlled trials with regard to the reduction of the incidence of stroke?

The results from several nonexperimental studies suggest that drug treatment of hypertension in daily clinical practice may not be as effective as in randomized controlled trials. These nonexperimental studies had limitations with regard to the selection of an appropriate control group. The objective of our study was to assess the effect of drug treatment of hypertension under circumstances of everyday medical practice on the incidence of stroke by using a prognostically comparable untreated reference group. Within two prospective, population-based cohort studies among 45,000 men and women 20 years of age and older in the Netherlands, we selected a cohort of 2,301 hypertensive subjects who either received drug treatment for hypertension (N = 1,318) or were untreated for hypertension but were determined to be "candidates" for drug treatment on the basis of their level of blood pressure and the presence of other cardiovascular risk factors (N = 983). Follow-up averaged 4.6 years and was complete for 91% of the hypertensives. Compared with untreated hypertensive subjects who were "candidates" for drug treatment, subjects who received drug treatment for hypertension had, after adjustment for potential confounders, a 39% [95% confidence interval (CI) = 3-61%] reduced risk of stroke. About 46 (95% CI = 29-599) hypertensive patients need to be treated with antihypertensive drugs for 5 years to prevent one stroke in the general Dutch population. When a prognostically comparable reference group is used, the drug treatment of hypertension under circumstances of everyday medical practice appears to be effective in the reduction of the incidence of stroke. The relative risk reduction that we found was similar to those found in randomized controlled trials.

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PubMed2001

Human brain chemical shift imaging at age 60 to 90: analysis of the causes of the observed sex differences in brain metabolites.

RATIONALE AND OBJECTIVES: To assess whether differences in cerebral atrophy and white matter lesions or in the presence of lactate and lipid signals can explain the observed differences in brain choline, creatine, and N-acetylaspartate levels between healthy elderly women and men. METHODS: In addition to standard magnetic resonance imaging of the brain, an 8 x 8 x 2-cm3 supraventricular transverse brain volume parallel to the canthomeatal line was examined by magnetic resonance spectroscopy (automated 1H chemical shift imaging) in 540 healthy elderly persons. RESULTS: At P = 0.01, 0.001, and 0.0001, choline differed between women and men in 14, 9, and 5 of 36 voxels, respectively. On correction for cerebral atrophy (more frequent in men than in women), white matter lesions (more frequent in women), and lactate and lipid (more frequent in women), the differences in choline were reduced to 13, 6, and 3. Sex differences for creatine and N-acetylaspartate were similar but less numerous after correction. CONCLUSIONS: Elderly women and men in the general population show differences in the levels of creatine, N-acetylaspartate, and especially choline in portions of the brain. The sex-related differences in brain metabolite levels cannot be explained by differences in cerebral atrophy or other aging-related phenomena (white matter lesions, lactate, lipid).

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PubMed2001

Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study.

OBJECTIVE: White matter lesions are often seen on MR scans of elderly non-demented and demented people. They are attributed to degenerative changes of small vessels and are implicated in the pathogenesis of cognitive decline and dementia. There is evidence that especially periventricular white matter lesions are related to cognitive decline, whereas subcortical white matter lesions may be related to late onset depression. The frequency distribution of subcortical and periventricular white matter lesions according to age and sex reported. METHODS: A total of 1077 subjects aged between 60-90 years were randomly sampled from the general population. All subjects underwent 1.5T MR scanning; white matter lesions were rated separately for the subcortical region and the periventricular region. RESULTS: Of all subjects 8% were completely free of subcortical white matter lesions, 20% had no periventricular white matter lesions, and 5% had no white matter lesions in either of these locations. The proportion with white matter lesions increased with age, similarly for men and women. Women tended to have more subcortical white matter lesions than men (total volume 1.45 ml v 1. 29 ml; p=0.33), mainly caused by marked differences in the frontal white matter lesion volume (0.89 ml v 0.70 ml; p=0.08). Periventricular white matter lesions were also more frequent among women than men (mean grade 2.5 v 2.3; p=0.07). Also severe degrees of subcortical white matter lesions were more common in women than in men (OR 1.1; 95% confidence interval (95% CI) 0.8-1.5) and periventricular white matter lesions (OR 1.2; 95% CI 0.9-1.7), albeit that none of these findings were statistically significant. CONCLUSIONS: The prevalence and the degree of cerebral white matter lesions increased with age. Women tended to have a higher degree of white matter lesions than men. This may underlie the finding of a higher incidence of dementia in women than in men, particularly at later age.

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PubMed2001

Aspirin use and risk of stroke in the elderly: the Rotterdam Study.

The objective of the study was to assess the association between aspirin use and the risk of stroke in a population-based study in the elderly. The study was carried out within the framework of the Rotterdam Study, a prospective population-based cohort study. In the total study population there was a weak, nonsignificant association between aspirin use and the risk of stroke (adjusted relative risk 1.29, 95% CI 0.91-1.83). Stratification by history of vascular diseases revealed that aspirin considerably increased the risk of first-ever stroke in subjects free from vascular disease (adjusted relative risk 1.80; 95% CI 1.03-3.13). In persons with vascular disease, no association was observed between aspirin use and risk of stroke (adjusted relative risk 0.99, 95% CI 0.56-1.73). Our findings suggest that aspirin use may increase the risk of stroke in elderly subjects free from vascular disease.

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PubMed2001

Prognosis of Alzheimer's disease: the Rotterdam Study.

The aim of this study was to construct a prognostic model to predict the progression of Alzheimer's disease (AD). Prevalent and incident cases with AD came from the Rotterdam Study, a population-based prospective cohort study of persons aged 55 years and older, including those living in institutions. Rate of cognitive decline, as measured by the Mini Mental State Examination (MMSE score), was predicted by a random effects model. Risk of institutionalization and death were estimated with polytomous logistic regression analysis. At baseline, 306 subjects were diagnosed with prevalent AD and had complete data on living conditions and cognitive function. After a mean follow-up of 2.1 years, 95 subjects with incident AD had been diagnosed. Prevalent patients showed a slower decline in cognitive function than incident patients (p = 0.004). For prevalent and incident AD patients, high age and low cognitive performance were the strongest predictors for institutionalization and death. These prognostic risk functions can provide information on the decline of Alzheimer patients and might be used to better evaluate the effect of treatments for AD.

Activities of Daily Living↗
PubMed2001

Is carotid intima-media thickness useful in cardiovascular disease risk assessment? The Rotterdam Study.

BACKGROUND AND PURPOSE: We determined the contribution of common carotid intima-media thickness (IMT) in the prediction of future coronary heart disease and cerebrovascular disease when added to established risk factors. METHODS: We used data from a nested case-control study comprising 374 subjects with either an incident stroke or a myocardial infarction and 1496 controls. All subjects were aged 55 years and older and participated in the Rotterdam Study. Mean follow-up was 4.2 years (range, 0.1 to 6.5 years). We evaluated which correlates of coronary heart disease and cerebrovascular disease contribute to the prediction of either a new incident myocardial infarction or a stroke. Logistic regression modeling and the area under the receiver operating characteristic curve (ROC area) were used to quantify the predictive value of the established risk factors and the added value of IMT. RESULTS: The ROC area of a model with age and sex only was 0.65 (95% CI, 0.62 to 0.69). Independent risk factors were previous myocardial infarction and stroke, diabetes mellitus, smoking, systolic blood pressure, diastolic blood pressure, and total and HDL cholesterol levels. These risk factors increased the ROC area from 0.65 to 0.72 (95% CI, 0.69 to 0.75). This model correctly predicted 17% of all subjects with coronary heart disease and cerebrovascular disease. When common carotid IMT was added to the previous model, the ROC area increased to 0.75 (95% CI, 0.72 to 0.78). When only the IMT measurement was used, the ROC area was 0.71 (95% CI, 0.68 to 0.74), and 14% of all subjects were correctly predicted. There was no difference in ROC area when different measurement sites were used. CONCLUSIONS: Adding IMT to a risk function for coronary heart disease and cerebrovascular disease does not result in a substantial increase in the predictive value when used as a screening tool.

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PubMed2001

Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies.

BACKGROUND: In epidemiological studies, within-person variability in plasma total homocysteine (tHcy) measurements may dilute the association of 'usual' levels of tHcy with risk of cardiovascular disease, referred to as 'regression dilution'. The aim of this report was to estimate the magnitude of regression dilution after varying intervals of follow-up. METHODS: Regression dilution ratios (RDR) for tHcy were calculated using replicate tHcy measurements obtained after 3, 6 and 8 years from the Rotterdam, Hordaland and Framingham studies, respectively, and after 3, 6, 9 and 12 years from the United Kingdom Prospective Study of type 2 Diabetes Mellitus (UKPDS). RESULTS: The RDR for tHcy decreased with increasing interval in the three population-based studies and in the UKPDS. Moreover, the rate of decline of the RDR in the population-based studies was similar to that obtained in the UKPDS. Using linear regression analysis for the population-based studies, these results suggest an RDR of 0.83 at 2 years, 0.71 at 6 years and 0.53 at 12 years. CONCLUSIONS: These results have important implications for the interpretation of prospective studies of tHcy and cardiovascular disease. Failure to correct for increasing regression dilution using lower RDRs for longer follow-up may underestimate the relative risks of cardiovascular disease associated with tHcy by about one-fifth after 2 years and one-half after 10 years.

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