http://repub.eur.nl/res/aut/3452/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/9560/ 2000-01-01T00:00:00Z The objective of this study was to investigate the longitudinal relation between the insulin-like growth factor I (IGF-I)/IGF-binding protein (IGFBP) system and cognitive function. The study population consisted of a sample of 186 healthy participants from the population-based Rotterdam Study, aged 55-80 yr. At baseline, we determined fasting blood levels of free and total IGF-I, IGFBP-1, and IGFBP-3. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive impairment at baseline (MMSE score of <26; 6% of the sample) and cognitive decline after, on the average, 1.9 yr of follow-up (drop in MMSE score of >1 point/year; 22% of the sample). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression, with adjustment for age, sex, education, body mass index, and fasting insulin levels. Total IGF-I appeared to be inversely related to cognitive impairment, although not significantly. Higher total IGF-I and the total IGF-I/IGFBP-3 ratio were associated with less cognitive decline (OR per SD increase = 0.65; 95% CI = 0.44-0.95 and OR = 0.59; 95% CI = 0.39-0.87, respectively). No relation was observed between free IGF-I and cognitive decline (OR = 0.99; 95% CI = 0.68-1.44). In conclusion, in this prospective study higher serum total IGF-I levels and higher total IGF-I/IGFBP-3 ratios, but not higher free IGF-I levels, were associated with less cognitive decline over the following 2 yr. Circulating total IGF-I levels may reflect an underlying biological process that influences cognitive decline. http://repub.eur.nl/res/pub/8867/ 1998-01-01T00:00:00Z 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. http://repub.eur.nl/res/pub/8913/ 1998-01-01T00:00:00Z The objective of this study was to investigate the relation between the peripheral concentrations of the adrenal steroid hormones cortisol and dehydroepiandrosterone sulfate (DHEAS) and cognitive impairment and decline. A prospective study design was used. The setting was a suburb of Rotterdam, The Netherlands. The study population consisted of a sample of 189 healthy participants from the population-based Rotterdam Study, aged 55-80 yr, who were invited for an additional examination. Follow-up examinations took place 1.9 yr after baseline, on the average. We determined fasting blood levels of DHEAS before dexamethasone administration and of cortisol and corticosteroid-binding globulin before and after the administration of 1 mg dexamethasone overnight. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognition. The associations with cognitive impairment (MMSE score of <26; 6% of the sample) and cognitive decline (drop in MMSE score of >1 point/yr; 24%) were estimated using logistic regression, with adjustment for age, sex, education, and depressive symptoms. An increase of 1 SD in the estimate of free cortisol (SD = 30.3) was associated with cognitive impairment, although not significantly [odds ratio (OR) = 1.5; 95% confidence interval (CI), 0.9-2.4]. A 1 SD increase in the natural logarithm of cortisol after the administration of 1 mg dexamethasone (SD = 0.68) was associated with an OR for cognitive decline of 1.5 (95% CI, 1.0-2.3). A 1 SD increase in DHEAS (SD = 2.10 micromol/L) was inversely, but nonsignificantly, related to cognitive impairment (OR = 0.5; 95% CI, 0.2-1.1) and cognitive decline (OR = 0.6; 95% CI, 0.4-1.1). The ratio of free cortisol over DHEAS was significantly related to cognitive impairment (OR = 1.8; 95% CI, 1.0-3.2). This prospective study among healthy elderly subjects suggested that basal free cortisol levels were positively related to cognitive impairment, and cortisol levels after dexamethasone treatment were related to cognitive decline. There was an inverse, but nonsignificant, association between DHEAS and cognitive impairment and decline. http://repub.eur.nl/res/pub/20348/ 1997-11-26T00:00:00Z Cognitive impairment is one of the major symptoms of dementia. The main cognitive functions acc orientation to time and place, recall and memory, attention, language, calculation, and visual construction. Impairment of cognitive functions influences the ability of an individual to live independently, and it diminishes the quality of life. In addition to the consequences for an individual, cognitive impairment imposes a major burden on the health care system because it induces an increased risk of institutionalization and hospitalization. Although cognlttve impairment is a less severe disorder than dementia, it is much more common. In a representative papu lation of subjects over 65 years of age, the prevalence of cognitive impairment was 15.8%, whereas the prevalence of dementia was 4.2%.' The risk of cognitive impairment rises exponentially with age. Therefore, we may expect an increase in the number of people with cognitive impairment in our aging society. At present, there acc a number of medications that can delay the progression of dementia and that can stabilize cognitive function. However, no cure or prevention for these disorders has been found yet. Therefore, it is important to identify modifiable risk factors for cognitive impairment and dementia. If these risk factors can be found, preventive intervention may become feasible.