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A Hofman

Publications and source records attributed to A Hofman.

At least 91 records · Page 5Linked to original sources

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.

Aged↗

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.

Age of Onset↗

The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women: a randomized controlled trial.

Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine levels in 121 perimenopausal women free of cardiovascular disease, and recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17 beta-estradiol and desogestrel (17 beta E(2)-D) and the placebo group and open with respect to a combination of conjugated equine estrogens and norgestrel (CEE-N). At baseline and after 6 months, fasting serum homocysteine levels were measured. Differences in 6 months serum homocysteine levels from baseline between treatment and placebo groups were calculated, and expressed as a percentage of the 6 months placebo level. After 6 months, the difference in serum homocysteine levels between women receiving 17 beta E(2)-D and placebo was -6.3% (95% CI, -12.4%; 0.0%, P=0.06). The difference between women receiving CEE-N and placebo was -10.1% (95% CI, -16.7%; -2.9%, P<0.01). The difference between the combined group of both types of hormone replacement therapy users and placebo was -7.8% (95% CI, -13.2%; -2.0%, P=0.01). No significant difference was observed between the two active regimens. Our results indicate that hormone replacement therapy decreases homocysteine levels in perimenopausal women.

Adult↗

Risk factors for age-related macular degeneration: Pooled findings from three continents.

OBJECTIVE: To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of population-based eye disease prevalence data. PARTICIPANTS: There were 14,752 participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME MEASURES: AMD diagnosis was made from masked grading of stereo macular photographs. Final classification of AMD cases was agreed by consensus between study investigators. RESULTS: AMD prevalence was strongly age related. Overall, AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years. Prevalence of neovascular AMD (NV) increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these age groups. There were no significant gender differences in the prevalence of NV or GA. Subjects in the Rotterdam population had a significantly lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only risk factor consistently associated with any form of AMD in all sites separately and in pooled analyses over the three sites. CONCLUSIONS: These combined data from racially similar communities across three continents provide strong and consistent evidence that tobacco smoking is the principal known preventable exposure associated with any form of AMD.

Adult↗

Evaluation of community-wide interventions: the ecologic case-referent study design.

In a setting of long-standing, community-wide and generally accepted prevention activities like youth health care services in The Netherlands, evaluative research in the form of experimental studies is hardly possible. Furthermore, as most interventions will bear fruit only after several years and the effects are often described in rather vague terms, even non-experimental study designs are fraught with possible difficulties. Although a study design using aggregate data is generally considered inferior or 'incomplete', in many cases, especially in health services research, this approach can be the only one feasible to evaluate the effectiveness of preventive programmes and interventions. In this article we present the ecologic case-referent design as a potentially expedient and valid method for estimating the ecologic effect of a population-wide intervention on the outcome rate in those populations. In this case-referent design, many variables are measured at the individual level, whereas the main exposure variable is measured at an aggregate or ecologic level. Using recently published studies as an example, the advantages and drawbacks of the design are discussed using the randomised controlled trial design as the referent study design.

Adolescent↗

Determinants of locomotor disability in people aged 55 years and over: the Rotterdam Study.

Locomotor disability, as defined by difficulties in activities of daily living related to lower limb function, can be the consequence of diseases and impairments of the cardiovascular, pulmonary, nervous, sensory and musculoskeletal system. We estimated the associations between specific diseases and impairments and locomotor disability, and the proportion of disability attributable to each condition, controlling for age and comorbidity. The Rotterdam Study is a prospective follow-up study among people aged 55 years and over in the general population. Locomotor disability in 1219 men and 1856 women was assessed with the Stanford Health Assessment Questionnaire. Diseases and impairments were radiological osteoarthritis, pain of the hips and knees, morning stiffness, fractures, hypertension, vascular disease, ischemic heart disease, stroke, heart failure, chronic obstructive pulmonary disease (COPD), depression, Parkinson's disease, osteoporosis, diabetes mellitus, overweight, and low vision. Adjusted odds ratios, etiologic and attributable fractions were calculated for locomotor disability. The occurrence of locomotor disability can partly be ascribed to joint pain, COPD, morning stiffness, diabetes and heart failure in both men and women. In addition in women osteoarthritis, osteoporosis, low vision, fractures, stroke and Parkinson's disease are significant etiologic fractions. In men with morning stiffness, joint pain, heart failure, diabetes mellitus, and COPD a significant proportion of their disability is attributable to this impairment. In women this was the case for Parkinson's disease, morning stiffness, low vision, heart failure, joint pain, diabetes, radiological osteoarthritis, stroke, COPD, osteoporosis, and fractures of the lower limbs, in that order. We conclude that locomotor complaints, heart failure, COPD and diabetes mellitus contribute considerably to locomotor disability in non-institutionalized elderly people.

Activities of Daily Living↗

A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study.

OBJECTIVE: To compare body mass index (BMI), waist-hip ratio (WHR) and waist circumference as predictors of all-cause mortality among the elderly. DESIGN: Population-based cohort study; mean follow-up was 5.4 y. SETTING: The Rotterdam Study. PARTICIPANTS: A total of 6296 men and women; baseline age 55-102 y. MEASUREMENTS: Sex-specific all-cause mortality was compared between quintiles of BMI, WHR and waist circumference and between predefined categories of BMI and waist circumference, stratified for smoking category. RESULTS: High quintiles of waist circumference, but not high quintiles of BMI and WHR were related to increased mortality among never smoking men, without reaching statistical significance. Only the highest category of BMI (BMI>30 kg/m2) among never smoking men was related to increased mortality, compared to normal BMI (hazard ratio 2.6 (95% confidence interval: 1.3-5.3)). Waist circumference between 94 and 102 cm and waist circumference 102 cm and larger were related to increased mortality, compared to normal waist circumference (hazard ratios 1.7 (95% confidence interval 1.1-2.8) and 1.6 (95% confidence interval 1.0-2.8), respectively). The proportion of mortality attributable to large waist circumference among never smoking men was three-fold the proportion attributable to high BMI. Among never smoking women and ex- and current smokers, categories of large body fatness did not predict increased mortality. CONCLUSION: Among never smoking elderly men waist circumference may have more potential for detecting overweight than the BMI.

Abdomen↗

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.

Aged↗

The prognosis of heart failure in the general population: The Rotterdam Study.

AIMS: To determine the prognosis, cause of death, and its determinants in participants of the population-based Rotterdam Study who were found to have heart failure. METHODS AND RESULTS: In 5255 Rotterdam Study participants (aged 68.9+/-8.6 years, 3113 women) the presence of heart failure was determined. Data were analysed with Cox's proportional-hazards models. One hundred and eighty-one participants (age 77.3+/-7.9 years, 109 women) had heart failure. Of these 85 (47%) died during the 4.8-8.5 (mean 6.1) years of follow-up. One, 2 and 5 years' survival was 89%, 79%, and 59%, representing an age-adjusted mortality twice that of persons without heart failure (hazard ratio 2.1, 95% CI 1.8-2.7). The hazard ratio for sudden death was even more pronounced: 4.8, (95% CI 2.6-8.7). Diabetes mellitus, impairment of renal function and atrial fibrillation were associated with a poor outcome. A higher blood pressure and body mass index conferred a more favourable prognosis in those with heart failure. CONCLUSION: Heart failure generally afflicts older subjects in the community, carries a poor prognosis, especially in the presence of concomitant diseases, and confers a fivefold increase in the risk of sudden death.

Aged↗

Impaired cognitive function and compliance with antihypertensive drugs in elderly: the Rotterdam Study.

BACKGROUND: To our knowledge, there are no epidemiologic studies on the association between cognitive impairment and noncompliance with antihypertensive therapy. We studied compliance with antihypertensive treatment in elderly patients with cognitive impairment. METHODS: The Rotterdam Study is a prospective community-based cohort study of 7983 residents > or = 55 years old. We studied 1979 participants in the study who had 2 consecutive Mini Mental State Examination (MMSE) assessments in the period from 1991 to 1996, who did not have dementia at baseline, and who had received 3 or more consecutive antihypertensive prescriptions for at least 6 months. We compared persons with MMSE scores < or = 25 on both assessments to persons with MMSE scores > 25 on both occasions. Compliance was estimated by dividing the number of days the subjects took antihypertensive drugs by the follow-up period in days, and it was expressed as a ratio between 0 and 1. We defined patients as compliant if they had a compliance ratio > or = 0.80 and as noncompliant if they had a compliance ratio < or = 0.50 during the study period. RESULTS: We followed-up on 1573 patients (mean age, 68 years) during an average period of 1609 days. The risk of noncompliance in cognitively impaired elderly subjects was 2.0 (95% confidence interval, 1.4 to 2.8) after adjustment for age, sex, education, income, living situation, and smoking. Stratification by living situation showed that the risk increase predominantly occurred in those who lived alone (odds ratio, 2.9; 95% confidence interval, 1.2 to 7.5). CONCLUSIONS: Cognitive function is an independent predictor of compliance with antihypertensive drugs in elderly patients who are living alone.

Aged↗

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).

Aged↗

Median, ulnar, and combined median-ulnar nerve injuries: functional outcome and return to productivity.

BACKGROUND: Forearm and wrist injuries are a common cause of morbidity and are often associated with suboptimal recovery of hand function. This study describes and compares outcome after median, ulnar, or combined median-ulnar nerve injuries. METHODS: Three hundred thirteen wrist and forearm nerve injuries operated on between 1980 and 1997 in a large university hospital were reviewed in relation to complications, return to work, and sensor and motor recovery. Of these 313 patients, 220 (age range, 5-73 years) met the inclusion criteria. RESULTS: Motor recovery, progress of sensory reinnervation, and number of severed structures were related to the type of injury (p < 0.05). Multiple linear regression analysis revealed a relation between the appearance of sensory reinnervation and motor recovery (beta = 0.02; 95% confidence interval, 0.01-0.04; p = 0.01). A probability of 24% of work loss, after a mean follow-up of 17.7 months, was found. Poor sensory and motor recovery were associated with work disability (odds ratio [OR], 2.9; p = 0.002; and OR, 2.9; p = 0.007, respectively). No relationship was found between type of injury and return to work (p = 0.47). Level of injury (OR, 2.6; p = 0.01), type of work (OR, 3.1; p = 0.002), number of complications (p < 0.001), and hand-therapy (OR, 0.24; p = 0.001) were found to influence return to work. CONCLUSION: It may be concluded that peripheral nerve injuries at the forearm level can result in substantial functional loss and have major social consequences. This study identified factors influencing return to work that can be used to optimize postoperative treatment strategy.

Adolescent↗

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.

Aged↗

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.

Aged↗

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↗

Association between arterial stiffness and atherosclerosis: the Rotterdam Study.

BACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted within the Rotterdam Study in >3000 elderly subjects aged 60 to 101 years. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity, and common carotid artery stiffness was assessed by measuring common carotid distensibility. Atherosclerosis was assessed by common carotid intima-media thickness, plaques in the carotid artery and in the aorta, and the presence of peripheral arterial disease. Data were analyzed by ANCOVA with adjustment for age, sex, mean arterial pressure, and heart rate. RESULTS: Both aortic and common carotid artery stiffness were found to have a strong positive association with common carotid intima-media thickness, severity of plaques in the carotid artery, and severity of plaques in the aorta (P: for trend <0.01 for all associations). Subjects with peripheral arterial disease had significantly increased aortic stiffness (P:=0.001) and borderline significantly increased common carotid artery stiffness (P:=0.08) compared with subjects without peripheral arterial disease. Results were similar after additional adjustment for cardiovascular risk factors and after exclusion of subjects with prevalent cardiovascular disease. CONCLUSIONS: This population-based study shows that arterial stiffness is strongly associated with atherosclerosis at various sites in the vascular tree.

Age Distribution↗

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.

Aged↗