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A J Slooter

Publications and source records attributed to A J Slooter.

At least 19 recordsLinked to original sources
PubMed2001

Apolipoprotein E and carotid artery atherosclerosis: the Rotterdam study.

BACKGROUND AND PURPOSE: Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery atherosclerosis. METHODS: A population-based cross-sectional study was performed on 5401 subjects. Atherosclerosis was noninvasively assessed by the common carotid artery intima-media wall thickness and the presence of plaques in the carotid arteries. The relationship of the 6 APOE genotypes with these 2 indicators was studied with linear and logistic regression analysis, respectively, with adjustments for age and sex. RESULTS: Carriers of the E2E3 genotype had a thinner intima-media wall thickness (mean difference, -0.02 mm; 95% CI, -0.03 to -0.01 mm) and fewer plaques (odds ratio for >3 plaques at 6 sites, 0.6; 95% CI, 0.4 to 0.8) than the most common group, E3E3. The E4E4 group had slightly more atherosclerosis, but this was not statistically significant. Adjusting for the level of the apolipoprotein E protein (apoE) in serum or total or HDL cholesterol did not essentially change these findings. CONCLUSIONS: Our results suggest that APOE*4 is not an important risk factor for carotid artery atherosclerosis. The inverse relationship of E2E3 with carotid artery atherosclerosis seems to be independent of serum apoE and total and HDL cholesterol levels. However, the low frequency, together with the small effects, implies that any protective effect of E2E3 on carotid artery atherosclerosis is limited.

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PubMed1999

Head trauma and risk of dementia and Alzheimer's disease: The Rotterdam Study.

OBJECTIVE: To investigate the relation between head trauma and incidence of dementia in a prospective population-based study. BACKGROUND: Whether head trauma increases the risk of dementia and AD remains controversial. It has been suggested that the risk might be particularly increased for carriers of the APOE-epsilon4 allele. METHODS: The study population included 6645 participants of the prospective population-based Rotterdam Study, aged 55 years or older, who were free of dementia at baseline. Head trauma with loss of consciousness was measured at baseline by a self-report to a physician and detailed the number of head traumas, time since head trauma, and duration of loss of consciousness. The cohort was followed for incident dementia that was diagnosed according to international criteria. Logistic regression was used to calculate the risk of dementia after adjusting for age, gender, and education. RESULTS: No increased risk of dementia or AD was found for persons with a history of head trauma with loss of consciousness (relative risk [RR] for dementia = 1.0, 95% CI, 0.5-2.0; RR for AD = 0.8, 95% CI, 0.4-1.9). Multiple head traumas, time since head trauma, and duration of unconsciousness did not significantly influence the risk of dementia. In addition, the APOE-epsilon4 allele did not modify the relationship. CONCLUSIONS: This study suggests that mild head trauma is not a major risk factor for dementia or AD in the elderly. In addition, this study does not concur with previous cross-sectional studies suggesting an interaction with the APOE genotype.

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PubMed1999

The effect of APOE on dementia is not through atherosclerosis: the Rotterdam Study.

The APOE genotype is involved in atherosclerosis, and atherosclerosis increases the risk of dementia, in particular among carriers of the APOE-epsilon4 allele. We studied, in a population-based setting (244 dementia cases; 1,002 nondemented controls), whether APOE is associated with dementia through atherosclerosis. As neither adjusting nor stratification for atherosclerosis altered the association of APOE with dementia, our study suggests that atherosclerosis is not an intermediate factor.

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PubMed1999

Apolipoprotein E genotype and progression of Alzheimer's disease: the Rotterdam Study.

The APOE*4 allele of the apolipoprotein E gene increases the risk of Alzheimer's disease (AD), but whether it also affects the course of the disease is controversial. However, all studies on this issue until now have been based on patients at various stages of disease. In the present population-based study, 97 patients were included at a similar stage, i.e., before the onset of symptoms, and followed for up to 5 years. We found that the APOE*4 allele is not a strong determinant of survival in AD. As change in cognitive function and severity of dementia are similar for AD patients with and without APOE*4, our study suggests that progression of AD is not related to the APOE*4 allele.

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PubMed1999

Estrogen use and early onset Alzheimer's disease: a population-based study.

Estrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of residence. Information on estrogen use and other risk factors were, for cases (n=109) and controls (n=119), collected from the next of kin by structured interview. The strength of the association between estrogen use and early onset Alzheimer's disease was studied using conditional logistic regression with adjustment for age and education level. There was an inverse association between estrogen use and early onset Alzheimer's disease (adjusted odds ratio 0.34; 95% confidence interval 0.12-0.94). The study therefore suggests that estrogen use is beneficial to Alzheimer's disease with early onset.

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PubMed1999

Genetic and environmental factors in Alzheimer's disease.

In recent years, considerable progress has been made in unraveling the etiology of Alzheimer's disease (AD). Dominant mutations have been identified, in the beta-amyloid precursor protein gene (APP), and in two homologous genes presenilin 1 (PSEN-1) and presenilin 2 (PSEN-2). The contribution of these mutations to the occurrence of AD in the general population is estimated to be lower than 1p. 100. A genetic risk factor of more importance on the population level is the Apolipoprotein E (APOE) gene that may explain up to 17p. 100 of the prevalence of AD in the general population. It is clear that other yet unknown genes must be involved in the etiology of AD. Two loci on chromosome 12 have been suggested, but no consistent effect could be found. Important progress with regard to non-genetic risk factors concerns the role of vascular and endocrine factors in the pathogenesis. Of major interest for the prevention of AD will be the interaction of genetic and non-genetic risk factors. Large scale, long term follow-up studies, ongoing at present, may clarify this issue.

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PubMed1998

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 Alzheimer's 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 Alzheimer's 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 Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's 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 Alzheimer's 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 Alzheimer's disease.

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PubMed1998

Serum apolipoprotein E level is not increased in Alzheimer's disease: the Rotterdam study.

The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in Alzheimer patients compared to non-demented controls (0.75 micromol/l (SD 0.35), vs. 0.83 micromol/l (SD 0.40), P < 0.05). This finding is in accordance with lower serum apoE levels as observed in carriers of the APOE*4 allele, who are over-represented in Alzheimer's disease. After adjustment for age, sex, total protein, albumin level, body mass index and the APOE genotype, the difference in serum apoE levels largely disappeared. Our population-based study suggests that the differences in serum apoE level between Alzheimer patients and controls are mainly the result of differences in the distribution of the APOE genotype.

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PubMed1998

Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study.

OBJECTIVES: To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes. DESIGN: Case-control study nested in a population-based cohort study with a mean (SD) follow-up of 2.1 (0.9) years. SETTING: General population in Rotterdam, the Netherlands. PARTICIPANTS: A total of 134 patients with incident dementia and a random sample of 997 nondemented control subjects. No participant had dementia at baseline. MAIN OUTCOME MEASURES: Odds ratios for dementia and Alzheimer disease, the fraction of dementia attributable to the APOE epsilon4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes. RESULTS: Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon4 allele was estimated to be 20%. The APOE genotypes explained up to 10% of the variance in age at the onset of dementia. The association between the epsilon4 allele and dementia was strongest in the youngest age category and in those with a family history of dementia. CONCLUSIONS: The APOE genotype is an important determinant of the risk of dementia. At a population level, however, other factors than the APOE genotype may play an important role in the cause of dementia.

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PubMed1998

Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam Study.

The apolipoprotein E4 allele (APOE epsilon 4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOE epsilon 4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline. The Mini Mental State Examination (MMSE) score at follow-up was studied as a function of APOE epsilon 4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOE epsilon 4 and for APOE epsilon 4 in the absence of atherosclerosis. APOE epsilon 4 carriers with two or more indicators of atherosclerosis positive, had a significantly lower MMSE score at follow-up (mean difference -0.7 points; 95% confidence interval -1.1 to -0.2) relative to non-APOE epsilon 4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOE epsilon 4 and atherosclerosis are not independent, and that particularly APOE epsilon 4 carriers with atherosclerosis are at increased risk of cognitive decline.

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PubMed1998

Risk of left ventricular dysfunction in patients with probable Alzheimer's disease with APOE*4 allele.

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.

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PubMed1997

Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation.

OBJECTIVE: To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). DESIGN AND SETTING: Population-based, case-control study from Rotterdam, the Netherlands, and New York City. PARTICIPANTS: A total of 187 patients with dementia and stroke were compared with 507 controls similar in age and ethnic group. MAIN OUTCOME MEASURES: The APOE allele frequencies in patients and controls; the odds ratio of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex, residency, and education; and the percent attributable risk related to the APOE epsilon4 allele. RESULTS: Overall, patients with dementia and stroke had a higher APOE epsilon4 allele frequency than controls. Compared with APOE epsilon3 homozygote individuals, APOE epsilon4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), while APOE epsilon4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated with APOE epsilon4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to the APOE epsilon4 allele among demented patients with stroke was 41% overall, 33% among those with VaD, and 44% among those with AD with CVD. CONCLUSION: The APOE epsilon4 allele is a genetic risk factor for dementia with stroke, including VaD and AD with CVD. This may imply shared genetic susceptibility to dementia associated with stroke and AD. Alternatively, the category of patients with dementia and stroke, including VaD as currently defined, may include patients with AD.

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PubMed1997

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, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's 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 Alzheimer's 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 Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimer's 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 Alzheimer's 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 Alzheimer's disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.

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