In order to achieve coordinated migration through extracellular matrix and endothelial barriers during metastasis, cancer cells must be endowed with specific structural and adhesive properties. In this context, comparison of the mechanical properties of transformed versus normal cells, on which little quantitative information is available, was the focus of this study. Normal human dermal fibroblasts and their SV40-transformed counterparts were analyzed using various manipulations. First, micropipet aspiration of suspended cells allowed calculation of a cortical tension (similar for normal and transformed cells), and an apparent viscosity (30% lower for transformed than for normal fibroblasts); in addition, transformed fibroblasts exhibited a more fragile surface than their normal counterparts. Second, tangential ultracentrifugation of adherent cells demonstrated cellular elongation in the direction of the centrifugal field and the existence of critical forces for cell detachment, around 10(-7) N: these were 1.6-fold greater for normal than for transformed cells. Finally, examination of the wrinkle patterns formed by cells plated on a deformable polydimethylsiloxane substrate, plus analysis of cell retraction caused by ATP treatment following detergent permeabilization showed that normal fibroblasts exhibited much more contractility than their transformed counterparts, which we characterized by a cell contraction rate. Such quantitative parameters which reveal differences in the mechanical behavior of normal and transformed cells may be used in the future as new markers of oncogenic transformation.

Biomechanical Phenomena↗

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Incidence of dementia: does gender make a difference?

Several studies suggested that women are at higher risk of dementia than men. However, that was based on rather limited data. We investigated possible gender differences in the incidence of dementia, Alzheimer's disease and vascular dementia, in the Rotterdam Study, a large population based prospective cohort study in the Netherlands of 7,046 persons aged 55 years and older, free of dementia at baseline. In 40,441 person-years of follow-up (mean 5.7 years) we identified 395 new cases of dementia (overall incidence: 9.8 per 1,000 person-years). Alzheimer's disease was the most frequent subtype of dementia (293 cases; 7.2 per 1,000). Vascular dementia was diagnosed in 57 participants (1.5 per 1,000). Overall, dementia incidence was similar for men and women (rate ratio women versus men: 1.00, 95% CI: 0.80-1.24). However, after 90 years of age dementia incidence declined in men but not in women (rate ratio 2.61, 95% CI: 1.04-6.56), in particular for Alzheimer's disease (rate ratio 5.79, 95% CI: 1.40-23.90). The overall incidence of vascular dementia was lower in women than in men (rate ratio 0.57, 95% CI: 0.34-0.97). This large population-based study suggests no gender differences in the incidence of dementia up to high age. After 90 years of age the incidence of Alzheimer's disease is higher for women than for men. The incidence of vascular dementia is higher for men than for women in all age groups.

Age Distribution↗

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Histamine H2 blocking drugs and the risk for Alzheimer's disease: the Rotterdam Study.

We investigated the cross-sectional relation of the use of histamine H2 blocking drugs and the risk for AD in the population based Rotterdam Study. AD was clinically diagnosed according to DSM-IIIR and NINCDS-ADRDA criteria. Data on medication used in the past week were obtained by having subjects show vials of medications and were classified according to the Anatomical Therapeutic Chemical (ATC) index. There were 7276 subjects with complete data, including 208 with AD and 378 H2 users (ATC code A0BA). Compared to the total cohort of non-H2 users, the relative risk (estimated as the odds ratio) for AD among those taking H2 blockers was 0.95 (95% confidence interval (CI) 0.52-1.75), after controlling for age, education, sex, history of stroke, and use of benzodiazepines and nonsteroidal antiinflammatory drugs. To address unmeasured confounding (by (contra) indication), we compared the risk of AD in H2 users with a subset of subjects using topical medications (ATC code D and S; n = 436). The adjusted OR in this comparison was 1.24 (95% CI 0.52-2.98). These results do not support the hypothesis that use of histamine H2 blocking drugs protect against AD.

Aged↗

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NSAIDs and incident Alzheimer's disease. The Rotterdam Study.

Recent studies suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimer's disease (AD). We investigated the relation of NSAID use over a 10-year period and the risk for incident AD using a nested case-control design in the population-based Rotterdam Study. The study was performed in 306 subjects; 74 Alzheimer patients diagnosed according to NINCDS-ADRDRA criteria and 232 age and sex-matched controls. NSAID use was abstracted from general practitioners' medical records and expressed as cumulative prescription days. The relative risk for AD associated with long-term use (> or = 2 months) was 0.95 (95% CI: 0.46-1.99) as compared to nonusers, after controlling for possible confounders. In a separate examination, subjects who had more than 6 months of prescription days had a reduced relative risk for AD (RR = 0.74 (95% CI: 0.20-2.72). In an age-stratified analysis the effect in long-term users was evident in those aged 85 and under; 0.53 (95% CI: 0.15-1.77). All risk estimates were lower when the last 2 years of exposure were excluded from the analyses. Our point estimates in subjects younger than 85 years and in subjects using NSAIDs for 6 months or more are consistent with the hypothesis that long-term use of NSAIDs reduces the risk for AD. However, overall there was no association between NSAID use and the risk for incident AD.

Aged↗

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Burden of mortality and morbidity from dementia.

The purpose of this study was to estimate severity-specific mortality and to quantify the global health burden of dementia by assessing the time spent disabled with dementia and the life years lost due to dementia. We used mortality data from the Rotterdam study, a population-based prospective study in the 55+-year age range to calculate overall and severity-specific excess mortality for the demented. Lost life years were calculated by decomposing the (mixed) Dutch life table of 1990-1992 in two populations, the demented and the healthy, using prevalence and excess (all cause) mortality. Healthy life loss was calculated by a modified Sullivan technique, weighting for disease severity. Our results indicated that mortality was increased in the demented, in all age, sex, and severity groups. Mortality rate ratios were 2.1 (men) and 2.3 (women), with ranges of 1.7-3.4 (men) and 2.0-3.1 (women), depending on severity. Fifty-five-year-old men lose 1.2 life years due to morbidity and mortality and 0.7 life years due to mortality resulting from dementia. Women lose 3.1 and 1.9 life years, respectively. This population-based study provides evidence that mortality is increased in the demented at all stages, including minimal dementia. The quantified health impact on the general population is in the same order as that of lung cancer or stroke.

Aged↗

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The new epidemic: frequency of dementia in the Rotterdam Study.

Dementia is one of the most frequent and devastating disorders in the elderly. Due to the increased longevity and the increasing number of elderly people in our society, it is emerging more and more as a major health problem. We quantified the frequency and lifetime risk of dementia, and of subtypes of dementia, in the Rotterdam Study, a population-based prospective cohort study among 7, 983 subjects over the age of 55 years. The overall prevalence was 6. 4% and the overall incidence 1 per 100 person-years. Both prevalence and incidence increased strongly with age. Typical incidence estimates for age 65, 75 and 95 are 1 per 1,000, 1 per 100 and 1 per 10 person-years. One in 6 men, and almost 1 in 3 women, will suffer at least some of their lifetime from dementia.

Age Factors↗

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Risk factors for vascular disease and dementia.

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.

Alzheimer Disease↗

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Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H-70 Study.

The association between blood pressure and dementia is debated. Results from population-based studies on blood pressure and dementia are inconclusive, and most are performed in subjects younger than 80 years of age. We examined the relation between blood pressure and dementia and the possible effect modification of this relation by age in a pooled dataset based on two prospective population-based studies. Subjects came from the Rotterdam study (n = 6,668), a longitudinal population-based study among subjects aged 55 years and over, and from the Gothenburg H-70 Study (n = 317), a study on subjects aged 85 years at baseline. Screening and diagnostic procedures for assessment of dementia were similar at baseline and follow-up and comparable between studies. We estimated relative risks of dementia using Cox proportional hazards regression analysis, adjusted for age, gender and study location. The average follow-up was 2.1 years. During this period, 196 subjects developed dementia. The risk of dementia decreased with increasing blood pressure level (per 10 mm Hg systolic blood pressure: RR = 0.93, 95% CI = 0.88-0.99; per 10 mm Hg diastolic blood pressure: RR = 0.89, 95% CI = 0.79-1.00). This association was confined to subjects who used anthypertensive medication. Persons who were demented at baseline had a stronger blood pressure decline during follow-up than those who were non-demented. This study suggests an inverse association between blood pressure and dementia risk in elderly persons on antihypertensive medication. Possibly, they may need higher blood pressure levels to maintain an adequate cerebral perfusion. Alternatively, lower blood pressure may be secondary to brain lesions in preclinical stages of dementia.

Age Factors↗

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Comparison between conventional audiometry and ERA of deaf children in a serial test.

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Adolescent↗