Cognitive decline in the elderly : epidemiologic studies on cognitive function and dementia

In the last decades, the awareness has grown among the public, as well as among health politicians, that dementia is highly prevalent in older age, that it causes much distress to patients and their families, and that it poses a large burden on public health care resources.Initially, research focused chiefly on Alzheimer's disease, the most frequent type of dementia. In recent years, there is also increasing interest in vascular dementia. The reasons for this are that vascular dementia may be more prevalent than previously recognized, that vascular causes may be involved in the clinical picture of other dementia syndromes as well, and, perhaps most importantly, that vascular causes of cognitive decline can potentially be influenced by available measures of intervention. In studies of the frequency and etiology of dementia, much emphasis has been put on differentiating demented subjects from cognitively unimpaired individuals. However, there is little evidence to support the idea of a sharp distinction between demented and non-demented persons. Cognitive impairment is a quantitative rather than a qualitative characteristic, and consequently its distribution in the population shows a continuum of severity. The fact that cognitive dysfunction is common in old age does not imply that it is intrinsic to aging; it may be normal in the sense of usual, not in the sense of natural This thesis focuses on epidemiologic studies on cognitive function and dementia. The main part is devoted to investigations of the relation between vascular risk factors and cognitive function; in these studies cognitive function was evaluated as a continuously distributed variable. In the other studies in this thesis, risk factors for dementia were investigated with dementia as a dichotomous outcome variable

Trends in stroke incidence rates and stroke risk factors in Rotterdam, the Netherlands from 1990 to 2008

Stroke incidence rates have decreased in developed countries over the past 40 years, but trends vary across populations. We investigated whether age-and-sexspecific stroke incidence rates and associated risk factors as well as preventive medication use have changed in Rotterdam in the Netherlands during the last two decades. The study was part of the Rotterdam Study, a large populationbased cohort study among elderly people. Participants were 10,994 men and women aged 55-94 years who were stroke-free at baseline. Trends were calculated by comparing the 1990 subcohort (n = 7516; baseline 1990-1993) with the 2000 subcohort (n = 2883; baseline 2000-2001). Poisson regression was used to calculate incidence rates and incidence rate ratios in age-and-sex-specific strata. We further compared the prevalence of stroke risk factors and preventive medication use in the two subcohorts. In the 1990 subcohort 467 strokes occurred during 45,428 person years; in the 2000 subcohort 115 strokes occurred in 18,356 person years. Comparing the subcohorts, incidence rates decreased by 34% in men, but remained unchanged in women. Blood pressure levels increased between 1990 and 2000, whereas the proportion of current cigarette smokers decreased in men, but not in women. There was a strong increase in medication use for treatment of stroke risk factors across all age categories in both sexes. Our findings suggest that in Rotterdam between 1990 and 2008 stroke incidence rates have decreased in men but not in women

Socioeconomic differences in stroke among Dutch elderly women: the Rotterdam Study

BACKGROUND AND PURPOSE: We sought to assess the association between socioeconomic status and the risk of stroke among elderly women. Methods--The association between socioeconomic status and stroke emerged in cross-sectional and longitudinal data on 4274 female participants of the Rotterdam Study, a prospective, population-based, follow-up study in the Netherlands among older subjects. RESULTS: A history of stroke was more common among women in lower socioeconomic strata. The same trend was observed for the relationship between the lowest socioeconomic groups and the incidence of stroke. Risk factors for stroke were not related to socioeconomic status in a consistent manner. Smoking, history of cardiovascular diseases, and overweight were more common in lower socioeconomic groups. However, socioeconomic differences in hypertension, antihypertensive drug use, prevalence of atrial fibrillation, and prevalence of left ventricular hypertrophy were not observed. The complex of established risk factors could only partly explain the association between socioeconomic status and stroke. CONCLUSIONS: There is a strong association among elderly women between socioeconomic status and stroke. The association could only partly be explained by known risk factors. Our findings indicate that not only the actual risk profile but also risk factors earlier in life may be of importance

J-shaped relation between blood pressure and stroke in treated hypertensives

The objective of this study was to investigate the relationship between hypertension and risk of stroke in the elderly. The study was performed within the framework of the Rotterdam Study, a prospective population-based cohort study. The risk of first-ever stroke was associated with hypertension (relative risk, 1.6; 95% CI, 1.2 t

Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy

Purpose: Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment. Patients and Methods: This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis. Results: The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance. Conclusion: Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting

Insulin resistance and the risk of stroke and stroke subtypes in the nondiabetic elderly

Insulin resistance, which plays a key role in the development of diabetes mellitus, is a putative modifiable risk factor for stroke. The aim of this study was to investigate if markers of insulin resistance were associated with risk of stroke in the general elderly population. This study was part of the large population-based Rotterdam Study and included 5,234 participants who were aged 55 years or older and stroke free and diabetes free at baseline (1997-2001). Fasting insulin levels and homeostasis model assessment for insulin resistance were used as markers for insulin resistance. Cox regression was used to determine associations between insulin resistance markers and stroke risk, adjusted for age, sex, and potential confounders. During 42,806 person-years of follow-up (median: 8.6 years), 366 first-ever strokes occurred, of which 225 were cerebral infarctions, 42 were intracerebral hemorrhages, and 99 were unspecified strokes. Fasting insulin levels were not associated with risk of any stroke, cerebral infarction, or intracerebral hemorrhage. Homeostasis model assessment for insulin resistance, which almost perfectly correlated with fasting insulin levels, was also not associated with risk of stroke or stroke subtypes. In conclusion, in this population-based cohort study among nondiabetic elderly, insulin resistance markers were not associated with risk of stroke or any of its subtypes

N-acetyltransferase 2 polymorphism in Parkinson's disease. The Rotterdam study

The N-acetyltransferase-2 gene (NAT-2) has been associated with Parkinson's disease. The genotype associated with slow acetylation has been reported to be increased in patients with Parkinson's disease. Three mutant alleles M1, M2, and M3 of NAT-2 were investigated in 80 patients with idiopathic Parkinson's disease and 161 age matched randomly selected controls from a prospective population based cohort study. The allelic frequencies and genotypic distributions in patients were very similar to those found in controls. In controls the frequency of the wild type allele increased significantly with age suggesting that the mutant alleles are associated with an increased risk of mortality. These findings suggest that NAT-2 polymorphism is not a major genetic determinant of idiopathic Parkinson's disease, but may be a determinant of mortality in the general population

Incidence, risk, and case fatality of first ever stroke in the elderly population. The Rotterdam Study

OBJECTIVE: To estimate the incidence, survival, and lifetime risk of stroke in the elderly population. METHODS: The authors conducted a study in 7,721 participants from the population based Rotterdam Study who were free from stroke at baseline (1990-1993) and were followed up for stroke until 1 January 1999. Age and sex specific incidence, case fatality rates, and lifetime risks of stroke were calculated. RESULTS: Mean follow up was 6.0 years and 432 strokes occurred. The incidence rate of stroke per 1,000 person years increased with age and ranged from 1.7 (95% CI 0.4 to 6.6) in men aged 55 to 59 years to 69.8 (95% CI 22.5 to 216.6) in men aged 95 years or over. Corresponding figures for women were 1.2 (95% CI 0.3 to 4.7) and 33.1 (95% CI 17.8 to 61.6). Men and women had similar absolute lifetime risks of stroke (21% for those aged 55 years). The survival after stroke did not differ according to sex. CONCLUSIONS: Stroke incidence increases with age, also in the very old. Although the incidence rate is higher in men than in women over the entire age range, the lifetime risks were similar for both sexes