http://repub.eur.nl/res/aut/949/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/23419/ 2011-02-01T00:00:00Z http://repub.eur.nl/res/pub/22474/ 2006-01-01T00:00:00Z CONTEXT: The recent focus on the development of preventive interventions for Alzheimer disease has fueled the search for biomarkers of presymptomatic disease. Patients with Alzheimer disease and mild cognitive impairment have marked atrophy of the hippocampus and amygdala compared with healthy elderly people. Whether atrophy of these structures is also present in persons without cognitive impairment who later develop dementia is unknown. OBJECTIVE: To assess whether volumetric assessment of the hippocampus and amygdala using magnetic resonance imaging (MRI) predicts dementia in elderly people without cognitive impairment. DESIGN: Longitudinal cohort study. SETTING: A general community in the Netherlands. PARTICIPANTS: Five hundred eleven persons, aged 60 to 90 years, free of dementia at baseline were followed up during 3043 person-years (mean per person, 6.0 years). We performed volumetric assessment of the hippocampus and amygdala, obtained information about daily memory problems, and performed extensive neuropsychological testing in all study participants. MAIN OUTCOME MEASURE: Dementia, as assessed by repeated neuropsychological screening and monitoring of medical records. RESULTS: Thirty-five persons developed dementia (26 with Alzheimer disease). Hippocampal and amygdalar volumes were strongly associated with the risk of dementia; the age-, sex-, and education-adjusted hazard ratio per 1-SD decrease in volume was 3.0 (95% confidence interval, 2.0-4.6) for the hippocampus and 2.1 (95% confidence interval, 1.5-2.9) for the amygdala. The hazard ratios associated with atrophy were similar in persons without memory complaints or low cognitive function at baseline. Compared with those remaining free of dementia, baseline brain volumes were 17% smaller in persons who received a clinical diagnosis of dementia within 2 to 3 years after MRI and still 5% smaller in those whose conditions were diagnosed 6 years after MRI. CONCLUSION: Atrophy of the hippocampus and amygdala on MRI in cognitively intact elderly people predicts dementia during a 6-year follow-up. http://repub.eur.nl/res/pub/13377/ 2004-05-01T00:00:00Z BACKGROUND: Increased levels of inflammatory proteins have been found in the brains and plasma samples of patients with dementia. Whether the levels of inflammatory proteins in plasma samples are elevated before clinical onset of dementia is unclear. OBJECTIVE: To determine whether high levels of inflammatory proteins in plasma samples are associated with an increased risk of dementia. DESIGN AND SETTING: A case-cohort study within the Rotterdam Study, a population-based prospective cohort study in the Netherlands. PARTICIPANTS: The source population comprises 6713 subjects who, at baseline (1990-1993), were free of dementia and underwent venipuncture. From these, we selected both a random subcohort of 727 subjects and 188 cases who had developed dementia at follow-up. MAIN OUTCOME MEASURES: The associations between plasma levels of alpha1-antichymotrypsin, C-reactive protein, interleukin 6, the soluble forms of intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 and the risk of dementia were examined using the Cox proportional hazards regression models. RESULTS: High levels of alpha1-antichymotrypsin, interleukin 6, and, to a lesser extent, C-reactive protein were associated with an increased risk of dementia; rate ratios per standard deviation increase were 1.49 (95% confidence interval, 1.23-1.81), 1.28 (95% confidence interval, 1.06-1.55), and 1.12 (95% confidence interval, 0.99-1.25), respectively. Similar associations were observed for Alzheimer disease, whereas rate ratios of vascular dementia were higher for alpha1-antichymotrypsin and C-reactive protein. Soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were not associated with dementia. CONCLUSION: Plasma levels of inflammatory proteins are increased before clinical onset of dementia, Alzheimer disease, and vascular dementia. http://repub.eur.nl/res/pub/10102/ 2003-01-01T00:00:00Z BACKGROUND: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. OBJECTIVE: To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance. DESIGN AND SETTING: Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia. PARTICIPANTS: Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol. MAIN OUTCOME MEASURE: Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall). RESULTS: Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewer words in delayed recall testing for the highest tertile compared with the lowest tertile. Similar inverse associations were found among bioavailable and free estradiol levels, hippocampal volumes, and memory. In men, no association was observed between estradiol levels and hippocampal volume, but a trend was found for higher levels of total estradiol to be associated with poorer memory performance. CONCLUSION: Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance. http://repub.eur.nl/res/pub/9925/ 2002-01-01T00:00:00Z CONTEXT: Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress. OBJECTIVE: To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease. DESIGN AND SETTING: The Rotterdam Study, a population-based, prospective cohort study conducted in the Netherlands. PARTICIPANTS: A total of 5395 participants who, at baseline (1990-1993), were aged at least 55 years, free of dementia, and noninstitutionalized and had reliable dietary assessment. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia. MAIN OUTCOME MEASURES: Incidence of Alzheimer disease, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria, associated with dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E. RESULTS: After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had Alzheimer disease. When adjustments were made for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease (rate ratios [RRs] per 1-SD increase in intake were 0.82 [95% confidence interval [CI], 0.68-0.99] and 0.82 [95% CI, 0.66-1.00], respectively). Among current smokers, this relationship was most pronounced (RRs, 0.65 [95% CI, 0.37-1.14] and 0.58 [95% CI, 0.30-1.12], respectively) and also was present for intake of beta carotene (RR, 0.49 [95% CI, 0.27-0.92]) and flavonoids (RR, 0.54 [95% CI, 0.31-0.96]). The associations did not vary by education or apolipoprotein E genotype. CONCLUSION: High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease. http://repub.eur.nl/res/pub/9942/ 2002-01-01T00:00:00Z In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors. http://repub.eur.nl/res/pub/9615/ 2001-01-01T00:00:00Z 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.