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Biomedical subjects

A Hofman

Publications and source records attributed to A Hofman.

At least 73 records · Page 4Linked to original sources
PubMed2002

The collagen Ia1 SP1 polymorphism is associated with differences in ultrasound transmission velocity in the calcaneus in postmenopausal women.

Bone mineral density (BMD) and fracture risk are under genetic control. An association of a G to T polymorphism in the Sp1 binding site of the collagen Ia1 (COLIa1) gene with the risk for fractures has been previously reported. This association is only partly explained by differences in BMD. Thus, we analyzed the relationship between the COLIa1 Sp1 polymorphism and ultrasound (US) transmission velocity (speed of sound; SOS) in bone. In a population-based sample of 740 women (aged 55-80 years) we determined COLIa1 genotype and US parameters in the calcaneus. SOS in the "GG" genotype group was 1522 +/- 31 m/sec, in the "GT" group, 1519 +/- 30 m/sec, and in the "TT" group 1508 +/- 30 m/sec (P = 0.01). While the difference between the GG and TT genotype groups corresponds to 0.5 SD or 1%, we observed an allele-dose-effect of 4.3 m/sec decrease in SOS per each copy of the "T" allele (P = 0.01). The differences remained significant after adjustment for BMD measured at the femoral neck. When we analysed 45 incident nonvertebral fractures in this group of women, we found the risk for fracture by COLIA1 Sp1 genotype to be partly explained by SOS differences as well as by BMD differences. Linear regression analysis showed a progressive negative slope of the regression line of SOS over age from "GG" over "GT" to "TT" genotype. These data indicate that the collagen Ia1 Sp1 polymorphism is associated with the modulus of elasticity of bone as determined in vivo by acoustical measurement. The relationship is independent of BMD and increases with age, contributing to an explanation of the increased fracture risk observed for this polymorphism.

Aged↗
PubMed2002

Bone mineral density and the risk of peripheral arterial disease: the Rotterdam Study.

Low estrogen exposure throughout life is thought to result in low bone mineral density (BMD) and an increased incidence of cardiovascular disease. In the Rotterdam Study we cross-sectionally examined the relation between BMD and peripheral arterial disease (PAD), as assessed by an ankle-arm index (AAI) of <0.9 in either leg. Data on BMD and PAD were available for 5268 individuals (3053 women, 2215 men). From the BMD, Z-scores were calculated and subsequently divided into tertiles. Logistic regression analysis was used to compute odds ratios (OR) for PAD in tertiles of BMD, using the upper tertile as a reference. When adjusting for age, women with a low femoral neck BMD had a significantly increased risk of PAD (OR = 1.49, 95% CI 1.16-1.91). This could not be found for men (1.14, 0.84-1.53). The mid-tertile did not differ from the reference in either men or women. In women, additional adjustment for several potential confounders resulted in a somewhat lowered risk estimate (1.35, 1.02-1.79). In contrast, no association between lumbar spine BMD and PAD could be observed in either men or women. Our study shows an association between low femoral neck BMD and PAD in women only, an association unlikely to be causal. Estrogen deficiency may be the common denominator in osteoporosis and PAD, resulting in clustering of these two major diseases in postmenopausal women.

Aged↗
PubMed2002

Hippocampal head size associated with verbal memory performance in nondemented elderly.

The hippocampus plays a crucial role in the consolidation of memory. Anatomically, the hippocampal head, body, and tail are connected to separate regions of the entorhinal cortex, which conveys processed information from the association cortices to the hippocampus. Little is known, however, about the functional segregation along its longitudinal axis. In the present study, we investigated whether the hippocampal head, body, or tail is selectively involved in verbal memory performance. A total of 511 nondemented participants, aged 60-90 years, underwent a three-dimensional HASTE brain scan in a 1.5-T MRI unit. Hippocampal volumes were measured by manual tracing on coronal slices. Segmentation was performed in anterior-posterior direction on the basis of predefined cutoffs allocating 35, 45, and 20% of slices to the head, body, and tail, respectively. Memory performance was assessed by a 15-word learning test including tasks of immediate and delayed recall. To analyze the association between head, body, and tail volumes and memory performance, we used multiple linear regression, adjusting for age, sex, education, and midsagittal area as a proxy for intracranial volume. Participants with larger hippocampal heads scored significantly higher in the memory test, most notably in delayed recall (0.41 word per SD increase in left hippocampal head (95% CI (0.16, 0.67)), 0.33 word per SD increase in right hippocampal head (95% CI 0.06, 0.59)). Our data suggest selective involvement of the hippocampal head in verbal memory, and add to recent findings of functional segregation along the longitudinal axis of the hippocampus.

Aged↗
PubMed2002

Bone mineral density and mortality in elderly men and women: the Rotterdam Study.

Recent studies have shown that a low bone mineral density (BMD) is associated with a higher risk of mortality. Most studies have investigated this relationship in women only and presented their risk estimates per standard deviation change in BMD. However, when using this approach, a BMD threshold might be missed when relative risks are presented in the traditional manner. Therefore, in this study our aim was to model the relation between BMD and all-cause mortality. In the Rotterdam Study, follow-up was complete for 5819 men and women aged > or =55 years for whom BMD data were available. During an average follow-up of 5.4 years, 399 men and 317 women died. We calculated BMD Z scores using measurements performed at the femoral neck. Cox proportional hazards regression was used to fit the model. An average BMD, reflected by a Z score = 0, was used as the reference. For women, no significant relationship between BMD and overall mortality was observed. For men, however, a cubic model best fitted the relationship under study, also after adjusting for age and body mass index (BMI). The risk of mortality increased when BMD was below average. Similar results were found when separate curves were made for diabetics and nondiabetics, smokers (ever or never), and tertiles of BMI. Excluding subjects who had suffered hip fractures, or adjusting for the number of drugs used and for lower limb disability, essentially did not change results. This suggests that low BMD is not mainly due to morbidity and impaired mobility in our cohort, which makes this a less likely explanation for the observed relation with mortality. The results of our study suggest that, in men, a nonlinear relationship between BMD and mortality exists, which is independent of comorbidity, whereas, in women, no significant relationship was observed.

Aged↗
PubMed2002

Carotid intima-media thickness at different sites: relation to incident myocardial infarction; The Rotterdam Study.

AIMS: We examined whether intima-media thickness of the common carotid artery, carotid bifurcation, internal carotid artery and the combined measure are predictive of future myocardial infarction and which of the measurements has the strongest predictive value. METHODS AND RESULTS: We used a case-cohort approach in the Rotterdam Study. Ultrasound images of the common carotid artery, carotid bifurcation and the internal carotid artery were made. We selected the first 194 myocardial infarctions in the total population (mean follow-up 4.6 years). Analyses were done using Cox regression with adjustment for age and sex. The risk ratios (RR) for myocardial infarction associated with mean maximum common carotid, bifurcation, internal carotid intima-media thickness and the combined measurements were 3.18 (95% confidence interval, 1.83-5.54), 4.11 (2.10-8.05), 5.31 (1.77-15.9) and 6.27 (3.27-12.0), respectively, for the highest compared to the lowest quartile. The RRs for myocardial infarction per standard deviation increase of common carotid, bifurcation, internal carotid artery and combined intima-media thickness were 1.44 (1.28-1.62), 1.34 (1.17-1.53), 1.12 (0.94-1.33) and 1.47 (1.31-1.65), respectively. The areas under the ROC curves for the three measurements and the combined measure were not significantly different. CONCLUSIONS: Increased carotid intima-media thickness is a strong predictor of future myocardial infarction and all measurement sites have the same ability to predict future myocardial infarction.

Aged↗
PubMed2002

Coronary calcification detected by electron-beam computed tomography and myocardial infarction. The Rotterdam Coronary Calcification Study.

AIMS: Available data are insufficient to determine the relation between coronary calcification and coronary events in the general population. We cross-sectionally examined the association between coronary calcification and myocardial infarction in the prospective Rotterdam Coronary Calcification Study. METHODS AND RESULTS: From 1997 onwards, subjects were invited for electron-beam computed tomography scanning to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2,013 participants with a mean age of 71 years (standard deviation, 5.7 years). A history of myocardial infarction prior to scanning was present in 229 subjects. Compared to subjects in the lowest calcium score category (0-100), the age-adjusted odds ratio for myocardial infarction in subjects in the highest calcium score category (above 2,000) was 7.7 (95% confidence interval, 4.1-14.5) for men, and 6.7 (95% confidence interval, 2.4-19.1) for women. Additional adjustment for cardiovascular risk factors only slightly altered the estimates. The association was observed across all age subgroups, i.e. also in subjects of 70 years and older. CONCLUSION: A strong and graded association was found between coronary calcification and myocardial infarction. The association remained at high ages.

Calcinosis↗
PubMed2002

Hypertension and cerebral white matter lesions in a prospective cohort study.

White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hyper tension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population-based studies. One-half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow-up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1-114.8] and 15.8 (95% CI 3.4-73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3-8.4 and 2.6, 95% CI 1.0-6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1-22.6) and 5.8 (95% CI 2.1-16.0), respectively. In conclusion, we found a relationship between long-standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline.

Age Factors↗
PubMed2002

Cerebral haemodynamics and depression in the elderly.

BACKGROUND: Evidence from epidemiological and neuroimaging studies suggests that cerebrovascular disease is associated with depressive disorders in the elderly, but the extent to which it contributes to the pathogenesis of late life depression is unclear. OBJECTIVE: To investigate the relation between cerebral haemodynamics and depression in a population based study, using transcranial Doppler ultrasonography. METHODS: Cerebral blood flow velocity and CO2 induced vasomotor reactivity in the middle cerebral artery were measured in 2093 men and women who participated in the Rotterdam study. All subjects were screened for depressive symptoms using the Center of Epidemiological Studies Depression scale, and those with a score of 16 or over had a psychiatric work up. In a semistructured interview, diagnoses of depressive disorders according to the DSM-IV and subthreshold depressive disorder were established. Analyses of covariance controlled for age, sex, stroke, cognitive score, and cardiovascular risk factors were used to compare means of haemodynamic variables. RESULTS: Subjects with depressive symptoms had reduced blood flow velocities (mean difference, -2.9 cm/s; 95% confidence interval (CI), -5.0 to -0.8; p = 0.008) and lower vasomotor reactivity (mean difference -0.5%/kPa; 95% CI, -1.0 to -0.05; p = 0.03). Blood flow velocity was reduced most in subjects suffering from a DSM-IV depressive disorder (mean difference, -4.9 cm/s; 95% CI, -8.5 to -1.4; p = 0.006). The overall reduction in vasomotor reactivity was accounted for by subjects with subthreshold depressive disorder. CONCLUSIONS: Depression in late life is associated with cerebral haemodynamic changes that can be assessed by transcranial Doppler ultrasonography. The observed reduction in cerebral blood flow velocity could be a result of reduced demand in more seriously depressed cases with a DSM-IV disorder, whereas reduced CO2 induced cerebral vasomotor reactivity is a possible causal factor for subthreshold depressive disorder.

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PubMed2002

Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans.

The beneficial health effects attributed to the consumption of fruit and vegetables are related, at least in part, to their antioxidant activity. Of special interest is the inverse relationship between the intake of dietary nutrients rich in polyphenols and cardiovascular diseases. This effect is attributed to polyphenols' ability to inhibit low-density lipoprotein (LDL) oxidation, macrophage foam cell formation and atherosclerosis. Pomegranate polyphenols can protect LDL against cell-mediated oxidation via two pathways, including either direct interaction of the polyphenols with the lipoprotein and/or an indirect effect through accumulation of polyphenols in arterial macrophages. Pomegranate polyphenols were shown to reduce the capacity of macrophages to oxidatively modify LDL, due to their interaction with LDL to inhibit its oxidation by scavenging reactive oxygen species and reactive nitrogen species and also due to accumulation of polyphenols in arterial macrophages; hence, the inhibition of macrophage lipid peroxidation and the formation of lipid peroxide-rich macrophages. Furthermore, pomegranate polyphenols increase serum paraoxonase activity, resulting in the hydrolysis of lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions. These antioxidative and antiatherogenic effects of pomegranate polyphenols were demonstrated in vitro, as well as in vivo in humans and in atherosclerotic apolipoprotein E deficient mice. Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic mice significantly inhibited the development of atherosclerotic lesions and this may be attributed to the protection of LDL against oxidation.

Animals↗
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.

Aged↗
PubMed2001

Is open-angle glaucoma associated with early menopause? The Rotterdam Study.

The authors examined the association between age at menopause and open-angle glaucoma among women aged > or = 55 years in the population-based Rotterdam Study (1990--1993). Information on age and type of menopause was obtained by interview. Subjects (n = 3,078) were stratified into three categories according to age at menopause: <45 years, 45--49 years, and > or = 50 years, with the last group serving as the reference group. Diagnosis of open-angle glaucoma was based on the presence of a glaucomatous visual field defect and glaucomatous optic neuropathy. Open-angle glaucoma was diagnosed in 78 women with a natural menopause and 15 women with an artificial menopause. In the category of natural menopause, women who went through menopause before reaching the age of 45 years had a higher risk of open-angle glaucoma than the reference group (odds ratio = 2.6; 95% confidence interval: 1.5, 4.8), after adjustment for age and use of hormone replacement therapy. Among women who went through menopause between the ages of 45 and 49 years, the odds ratio was 1.1 (95% confidence interval: 0.7, 2.0). These findings suggest that early menopause is associated with a higher risk of open-angle glaucoma.

Adult↗
PubMed2001

Dietary antioxidants and peripheral arterial disease : the Rotterdam Study.

This study examined cross-sectionally the association of dietary beta-carotene, vitamin C, and vitamin E with peripheral arterial disease in Rotterdam, the Netherlands (1990--1993). The 4,367 subjects from the Rotterdam Study were aged 55--94 years and had no previous cardiovascular disease at baseline. Diet was assessed with a food frequency questionnaire. Peripheral arterial disease was defined as an ankle-arm systolic blood pressure index (AAI) of < or = 0.9 and was present in 204 men and 370 women. In multivariate-adjusted logistic regression analyses, vitamin C intake was significantly inversely associated with peripheral arterial disease in women (highest vs. lowest quartile: relative risk = 0.64, 95% confidence interval (CI): 0.48, 0.89; p(trend) = 0.006), and a 100-mg increase in intake was associated with a 0.013 AAI increase (95% CI: 0.001, 0.025). In men, vitamin E intake was inversely associated with peripheral arterial disease (relative risk = 0.67, 95% CI: 0.44, 1.03; p(trend) = 0.067); a 10-mg increase in intake was associated with a 0.015 AAI increase (95% CI: 0.001, 0.031). Whether these differences in antioxidant intake and the risk of a low AAI and of peripheral arterial disease between sexes are attributable to a different food pattern for men compared with women remains to be elucidated.

Aged↗
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.

Aged↗
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.

Aged↗
PubMed2001

Prevalence and causes of visual field loss in the elderly and associations with impairment in daily functioning: the Rotterdam Study.

OBJECTIVES: To determine the prevalence and causes of visual field loss (VFL) and the association between VFL and indicators of impairment in daily functioning. DESIGN: Population-based cohort study. SETTING: Suburb of Rotterdam, the Netherlands. PARTICIPANTS: Community-dwelling elderly residents (n = 6250). MAIN OUTCOME MEASURE: Visual field loss on suprathreshold static, Goldmann kinetic perimetry, or both. METHODS: Suprathreshold testing of the central visual field was performed on both eyes and repeated if results were abnormal or unreliable. Goldmann perimetry was performed to confirm defects. Causes were determined using ophthalmologic and neurologic examination data and medical records. Impairment was assessed using data from interviews and medical records on disability in daily life, falling, and fractures. RESULTS: The overall prevalence of VFL was 5.6% (3.0% in those aged 55-64 years to 17.0% in those > or =85 years); glaucoma was the leading cause in all age groups. Before age 75 years, other optic nerve diseases and stroke ranked second and third, respectively, as did age-related macular degeneration and retinal vascular occlusive disease, respectively, after this age. Also, after adjustment for visual acuity, VFL was associated with disability, diminished enjoyment of reading and watching television, and a higher risk of incident falling. Risk of incident hip fracture was not increased. CONCLUSIONS: Visual field loss is present in 1 of every 20 community-dwelling elderly people and is associated with impaired daily functioning. Glaucoma is the leading cause in all age groups. Other high-ranking causes, some of which are partly preventable, vary by age.

Activities of Daily Living↗
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↗