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Biomedical subjects

M M Breteler

Publications and source records attributed to M M Breteler.

At least 37 records · Page 2Linked to original sources
PubMed2001

Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study.

Insulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we examined the relationship of insulin resistance (measured by postload insulin) with levels of markers of inflammation and cellular adhesion molecules in a random sample of 574 nondiabetic elderly men and women participating in the Rotterdam Study. Associations were assessed by regression analysis, with ln-insulin as the dependent variable [regression coefficient (95% confidence interval)]. In our population, insulin was strongly and significantly (P < 0.001) associated with the markers of inflammation C-reactive protein [1.52 (0.96-2.08)], alpha-1-antichymotrypsin [1.25 (0.82-1.69)], and IL-6 [2.60 (1.69-3.52)], adjusted for age and gender. Associations weakened, to some extent, after additional adjustment for measures of obesity, smoking, and cardiovascular disease. Insulin was associated with the soluble intercellular adhesion molecule 1 [2.22 (1.29-3.16; P < 0.001)], whereas no association with the soluble vascular cell adhesion molecule 1 was found. The strength of the associations of insulin with C-reactive protein, alpha-1-antichymotrypsin, IL-6, and soluble intercellular adhesion molecule 1, as assessed by standardized regression coefficients, was comparable with the strength of the associations of insulin with high-density lipoprotein cholesterol, body mass index, and waist-to-hip ratio. The results of this population-based study indicate that low-grade inflammation and the cellular adhesion molecule soluble intercellular adhesion molecule 1 are an integral part of insulin resistance in nondiabetic elderly. These factors may contribute to the well-known relationship between insulin resistance and cardiovascular disease risk and might potentially become therapeutic targets in insulin resistant subjects.

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PubMed2001

The cost of treatment of Alzheimer's disease in The Netherlands: a regression-based simulation model.

OBJECTIVE: To examine the potential economic impact of treatment of Alzheimer's disease. DESIGN: Regression-based simulation estimation of the long term costs of Alzheimer's disease under a number of treatment scenarios. Data from an epidemiological study conducted in Rotterdam, The Netherlands, was used to simulate disease progression. Comparison of the costs and effectiveness experienced by the patients were used to measure the impact of treatment. PATIENTS AND INTERVENTION: 2 theoretical cohorts of patients with Alzheimer's disease, one of which receives standard treatment, while the other receives a treatment which slows cognitive decline as measured by the Mini-Mental State Examination (MMSE). MAIN OUTCOME MEASURES AND RESULTS: Under one of the scenarios examined, the baseline cost of Alzheimer's disease was 97,866 euro (EUR; 1996 values) per patient over 10 years' follow-up; the cost was almost EUR100,000 under all scenarios. Life expectancy following onset was about 4.5 years and MMSE decline was approximately 2 points per year for a typical prevalent (existing) patient and almost twice as much for incident (newly diagnosed) patients (1.82 vs 3.42 points per year, respectively). Slowing the rate of cognitive decline results in a slightly increased life expectancy, with more time being spent at home and less in a nursing home. Total costs (excluding those of therapy) will decrease, but savings will be modest and may well be less than the cost of therapy. Under the same scenario, total savings were EUR1,571 per patient which corresponds to an annual break-even cost of just EUR453. Decisions regarding the initiation or termination of therapy will affect both the number of patients treated and the costs and potential savings of treatment. CONCLUSIONS: The savings made in treating Alzheimer's disease will almost certainly be small in comparison with total costs and may well be offset by the cost of the treatment itself. Simulation models can be used to estimate the effect of therapy on the costs of care and can be useful tools in clinical decision-making and allocation of resources. These results show the need for further research into the costs and effects of treatment of Alzheimer's disease.

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PubMed2000

The alpha2-macroglobulin gene in AD: a population-based study and meta-analysis.

BACKGROUND: Whereas several authors recently reported a positive association between the alpha2-macroglobulin gene (A2M) and late-onset AD (LOAD), others were unable to replicate these findings. Early-onset AD (EOAD) is defined as onset age <65 years. Virtually all patients with LOAD are >65 years of age. OBJECTIVE: To evaluate the role of A2M in AD, the authors conducted a population-based study of EOAD and LOAD as well as a meta-analysis of all studies conducted to date. METHODS: Patients with EOAD (n = 100) were derived from a population-based study in four northern provinces of the Netherlands and the area of metropolitan Rotterdam. Patients with LOAD (n = 344) were drawn from the Rotterdam Study, a population-based prospective study on residents aged 55 years and over of a Rotterdam suburb in the Netherlands. Two polymorphisms were studied, A2M-I/D and A2M-Ile1000Val, in relation to the APOE epsilon4 allele (APOE*4). RESULTS: No genotypic or allelic association was found for either polymorphism in the population-based series of patients with LOAD. In patients with EOAD without APOE*4, a significant increase of carriers of A2M-1000Val was found. The meta-analysis of available published case-control data on these polymorphisms in white and mixed ethnic populations yielded no significant differences between cases and controls. Pooling the Asian studies conducted to date showed a significant decrease in the frequency of A2M-D among patients. CONCLUSIONS: These results suggest that A2M is not genetically associated with LOAD in white patients or mixed populations as found in the United States. In these populations A2M does not have clinical relevance. From a scientific perspective, the findings on EOAD and Asian patients require replication and further research in the A2M region.

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PubMed2000

Atrial fibrillation and the risk of cerebral white matter lesions.

BACKGROUND: Cerebral white matter lesions are often observed on MRI scans of elderly nondemented and demented persons. Their pathogenesis is not fully understood but cerebral hypoperfusion may be involved. Atrial fibrillation is a common finding in elderly subjects and may lead to a reduced cardiac output with cerebral hypoperfusion. The authors investigated the association between atrial fibrillation and the presence of white matter lesions. METHODS: From 1995 through 1996, the authors randomly sampled 1077 subjects from two ongoing prospective population-based studies. From each participant, an electrocardiogram (ECG) was recorded; atrial fibrillation and left ventricular hypertrophy were diagnosed with a computer program. For one of the two groups (553 subjects), earlier ECGs were available (mean follow-up 4.7 years). All subjects underwent 1.5-T MRI scanning; white matter lesions were separately rated for the periventricular and subcortical regions. RESULTS: The prevalence of atrial fibrillation was 1.9% among subjects younger than 75 years and 5.5% in subjects older than 75 years. The total number of subjects with atrial fibrillation was 28. Subjects with atrial fibrillation had severe periventricular white matter lesions more than twice as often as subjects who did not (RR 2.2; 95% CI 1.0 to 5.2) but had no increased risk of subcortical white matter lesions (RR 1.1; 95% CI 0.4 to 2.6). For seven subjects with atrial fibrillation both at baseline and at follow up, these relative risks were 6.3 (95% CI 1.1 to 37.1) and 0.7 (95% CI 0.1 to 3.7). CONCLUSIONS: Atrial fibrillation is associated with periventricular white matter lesions, but not with subcortical white matter lesions.

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PubMed2000

APOE and the risk of PD with or without dementia in a population-based study.

OBJECTIVE: To study the association between APOE genotype and PD with or without dementia. METHODS: The study formed part of the Rotterdam Study, a prospective, population-based cohort study on the frequency, etiology, and prognosis of chronic diseases. The cohort examined for PD consisted of 6,969 independently living or institutionalized inhabitants from a suburb of Rotterdam, the Netherlands, aged 55 years or older. All participants were screened at baseline (1990 to 1993) and at follow-up (1993 to 1994) for symptoms of parkinsonism by study physicians; screen positives received a diagnostic workup by a neurologist. RESULTS: APOE genotyping was available for 107 PD patients (26 with and 81 without dementia) and 4,805 non-PD control subjects. The presence of at least one epsilon2 allele significantly increased the risk of PD (OR = 1.7; 95% CI, 1.0 to 2.8). When we looked separately for demented and nondemented PD patients as compared with nonparkinsonian controls, APOE did not appear to be associated with PD without dementia, but both the epsilon2 and the epsilon4 allele increased the risk of PD with dementia (OR = 5.6; 95% CI, 2.0 to 15.2 and OR = 3.6; 95% CI, 1.3 to 9.9). The risk of dementia for epsilon4 allele carriers was not significantly different for persons with or without PD. However, the epsilon2 allele strongly increased the risk of dementia in patients with PD (interaction p < 0.007). CONCLUSIONS: In the elderly the APOE-epsilon2 allele increases the risk of PD and, in particular, the risk of PD with dementia.

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PubMed2000

Cerebral CO2 reactivity, cholesterol, and high-density lipoprotein cholesterol in the elderly.

Cholesterol and its subfractions play a role in the development of atherosclerosis. Cerebral CO2 reactivity reflects the compensatory capacity of cerebral arterioles. The authors investigated the relationship between total cholesterol, high-density lipoprotein (HDL), their ratio, and cerebral CO2 reactivity in 826 participants from the Rotterdam Study. Cerebral CO2 reactivity increased significantly with increasing levels of HDL and decreased significantly with an increasing total cholesterol/HDL ratio. This suggests that blood lipids may also affect smaller cerebral blood vessels.

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PubMed2000

Cerebral white matter lesions and depressive symptoms in elderly adults.

BACKGROUND: There is evidence for a vascular cause of late-life depression. Cerebral white matter lesions are thought to represent vascular abnormalities. White matter lesions have been related to affective disorders and a history of late-onset depression in psychiatric patients. Their relation with mood disturbances in the general population is not known. We investigated the relation between white matter lesions and the presence of depressive symptoms or a history of depression in a population-based study. METHODS: In a sample of 1077 nondemented elderly adults, we assessed the presence and severity of subcortical and periventricular white matter lesions using magnetic resonance imaging, presence of depressive symptoms, and history of depression. Using multiple regression analysis, we examined the relation among white matter lesions, depressive symptoms, and history of depression. RESULTS: Most of the subjects had white matter lesions. Persons with severe white matter lesions (upper quintile) were 3 to 5 times more likely to have depressive symptoms as compared with persons with only mild or no white matter lesions (lowest quintile) (periventricular odds ratio [OR] = 3.3; 95% confidence interval [CI], 1.2-9.5; subcortical OR = 5.4; 95% CI, 1.8-16.5). In addition, persons with severe subcortical but not periventricular white matter lesions were more likely to have had a history of depression with an onset after age 60 years (OR = 3.4; 95% CI, 1.1-10.7) compared with persons with only mild or no white matter lesions. CONCLUSION: The severity of subcortical white matter lesions is related to the presence of depressive symptoms and to a history of late-onset depression.

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PubMed2000

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

Cerebral white matter lesions (WMLs) have been associated with cognitive dysfunction. Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain. In addition, it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed. We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects randomly sampled from the general population. Quantification of WMLs was assessed by means of an extensive rating scale on 1.5-T magnetic resonance imaging scans. Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed, memory performance, and global cognitive function. When analyzed separately, both periventricular and subcortical WMLs were related to all neuropsychological measures. When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa, the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared. Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed, and more than 0.5 SD below average for global cognitive function. Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks.

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PubMed2000

Carotid atherosclerosis and cerebral white matter lesions in a population based magnetic resonance imaging study.

Cerebral white matter lesions are frequently observed on magnetic resonance imaging of elderly, nondemented persons. There is evidence that white matter lesions are involved in the pathophysiology of cognitive decline and dementia. White matter lesions can be divided into those in the periventricular and those in the subcortical region. Pathological and epidemiological studies suggest that atherosclerosis is involved in the pathogenesis of these lesions. Our study reports on the association between atherosclerosis in the carotid arteries and white matter lesions in a population-based study among 1077 elderly subjects. We randomly sampled 1077 subjects aged between 60-90 years from two prospective population-based studies. All subjects underwent ultrasonography of the carotid artery. In addition, 1.5 T magnetic resonance imaging was performed; white matter lesions in the subcortical and periventricular regions were rated separately. With increasing number of plaques in the carotid artery the severity of periventricular white matter lesions increased (Ptrend = 0.03), but not the severity of subcortical white matter lesions (Ptrend = 0.19). In addition, an increase in intima media thickness was borderline significantly associated with an increased severity of periventricular white matter lesions (Ptrend = 0.09), but not of subcortical white matter lesions (Ptrend = 0.68). These findings suggest that partly dissimilar pathogenetic mechanisms are involved in the etiology of periventricular and subcortical white matter lesions.

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PubMed2000

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.

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PubMed2000

Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study.

UNLABELLED: AIMS AND SUBJECTS: We investigated the prospective relationship between thyroid status and the risk of dementia and Alzheimer's disease among a random sample of 1843 participants, aged 55 years and over, from the population-based prospective Rotterdam Study. METHODS: Thyroid status was measured at baseline (1990-93), through assessment of serum antibodies to thyroid peroxidase (TPO-Abs, positive: >10 IU/ml), serum TSH levels, and when TSH was abnormal (<0.4 or >4.0 mU/l), serum thyroxin levels (T4). At baseline and at follow up, after on average 2 years, participants were screened for dementia. Diagnoses were based on international criteria. RESULTS: Persons with reduced TSH levels at baseline had a more than threefold increased risk of dementia (RR = 3.5, 95%CI: 1.2-10.0) and of Alzheimer's disease (RR = 3.5, 95%CI: 1.1-11.5), after adjustment for age and sex. Among persons with reduced TSH levels, T4 levels appeared to be positively related to the risk of dementia (RR per SD increase = 2.9, 95%CI: 0.7-12.2), although none of those who became demented had a T4 level above the normal range (>140 nmol/l). The risk of dementia was especially increased in subjects with low TSH who were positive for TPO-Abs (RR = 23.7, 95%CI: 4.0-140). CONCLUSIONS: This is the first prospective study to suggest that subclinical hyperthyroidism in the elderly increases the risk of dementia and Alzheimer's disease.

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PubMed2000

Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly.

BACKGROUND AND PURPOSE: MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions. METHODS: We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531 subjects in late life. RESULTS: The presence of aortic atherosclerosis during midlife was significantly associated with the presence of periventricular white matter lesions approximately 20 years later (adjusted relative risk, 2.4; 95% CI, 1.2 to 5.0); the relative risks increased linearly with the severity of aortic atherosclerosis. No association was found between midlife aortic atherosclerosis and subcortical white matter lesions (adjusted relative risk, 1.1; 95% CI, 0.5 to 2.3) or between late-life aortic atherosclerosis and white matter lesions. CONCLUSIONS: The pathogenetic process that leads to cerebral periventricular white matter lesions starts already in or before midlife. The critical period for intervention directed at prevention of white matter lesions and its cognitive consequences may be long before these lesions become clinically detectable.

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PubMed2000

A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly.

The objective of this study was to investigate the longitudinal relation between the insulin-like growth factor I (IGF-I)/IGF-binding protein (IGFBP) system and cognitive function. The study population consisted of a sample of 186 healthy participants from the population-based Rotterdam Study, aged 55-80 yr. At baseline, we determined fasting blood levels of free and total IGF-I, IGFBP-1, and IGFBP-3. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive impairment at baseline (MMSE score of <26; 6% of the sample) and cognitive decline after, on the average, 1.9 yr of follow-up (drop in MMSE score of >1 point/year; 22% of the sample). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression, with adjustment for age, sex, education, body mass index, and fasting insulin levels. Total IGF-I appeared to be inversely related to cognitive impairment, although not significantly. Higher total IGF-I and the total IGF-I/IGFBP-3 ratio were associated with less cognitive decline (OR per SD increase = 0.65; 95% CI = 0.44-0.95 and OR = 0.59; 95% CI = 0.39-0.87, respectively). No relation was observed between free IGF-I and cognitive decline (OR = 0.99; 95% CI = 0.68-1.44). In conclusion, in this prospective study higher serum total IGF-I levels and higher total IGF-I/IGFBP-3 ratios, but not higher free IGF-I levels, were associated with less cognitive decline over the following 2 yr. Circulating total IGF-I levels may reflect an underlying biological process that influences cognitive decline.

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PubMed2000

Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The last comparison of prevalence figures of dementia across European studies was 10 years ago. Using studies conducted in the 1990s, the authors compare the age- and sex-specific prevalence of dementia, AD, and vascular dementia (VaD) across European population-based studies of persons 65 years and older. Data from these studies were also pooled to obtain stable estimates of age- and sex-specific prevalence. A total of 2346 cases of mild to severe dementia were identified in 11 cohorts. Age-standardized prevalence was 6.4% for dementia (all causes), 4.4% for AD, and 1.6% for VaD. The prevalence of dementia increased continuously with age and was 0.8% in the group age 65 to 69 years and 28.5% at age 90 years and older. The corresponding figures for AD (53.7% of cases) were 0.6% and 22.2%, and for VaD (15.8% of cases), 0.3% and 5.2%. Variation of AD prevalence across studies was greatest for men. In the VaD subtype, a large variation across studies was observed, as well as a difference in prevalence between men and women that was age dependent. Dementia is more prevalent in women, and AD is the main contributor to the steep increase of prevalence with age.

Age Factors↗
PubMed2000

Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men. There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries. This study confirms that AD is the most frequent dementing disorder in all ages, and that there is a higher incidence of dementia, specifically AD, in women than men among the very old. Finally, there may be regional differences in dementia incidence.

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PubMed2000

Prognosis with dementia in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The effect of dementia on time to death and institutionalization in elderly populations is of importance to resource planning, as well as to patients and their carers. The authors report a collaborative reanalysis of nine population-based studies conducted in Europe to compare dementia cases and noncases in risk of and time to death and to institutionalization. Prevalent and incident cases were more likely than noncases to reside in an institution at baseline and were more likely to enter institutional care. Prevalent cases also had over twice the risk of death compared to noncases and survival for men with dementia was consistently lower than that for women with dementia of the same age group.

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PubMed2000

Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The results of seven population-based studies were examined separately and pooled to obtain age- and sex-specific estimates of the prevalence of PD. An in-person screening instrument and diagnostic clinical examination were used to detect potential PD cases. The overall prevalence (per 100 population) in persons 65 years of age and older was 1.8, with an increase from 0.6 for those age 65 to 69 years to 2.6 for those 85 to 89 years. There were no sex differences in prevalence of PD.

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