Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease

BACKGROUND: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. METHODS: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. RESULTS: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. CONCLUSIONS: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia

Reproductive period and risk of dementia in postmenopausal women

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

Verbetert paracetamol het herstel na een beroerte?

An increase in body temperature in the first days following stroke is related to poor functional outcome. High-dose paracetamol (acetaminophen) reduces the body temperature by 0.3°C and can prevent fever. Paracetamol treatment is simple, cheap and has few side effects. In the first "Paracetamol (Acetaminophen) in Stroke" (PAIS) study, there was a beneficial effect of high-dose paracetamol on functional outcome in patients with stroke and a body temperature of 37.0°C or above. Because this result was found in a subgroup analysis, a new study is needed to confirm this finding. Recently the randomised PAIS 2 study was initiated. This study aims to assess the effect of high-dose paracetamol on functional outcome in patients with acute stoke and a body temperature of 37.0°C or above.Een stijging van de lichaamstemperatuur in de eerste dagen na een beroerte is geassocieerd met een slechte prognose. Hoge dosis paracetamol verlaagt de lichaamstemperatuur gemiddeld met 0,3°C en kan koorts voorkómen. Behandeling met paracetamol is eenvoudig, zeer goedkoop en heeft weinig bijwerkingen. In het eerste ‘Paracetamol (Acetaminophen) in Stroke’(PAIS)-onderzoek verbeterde vroege behandeling met een hoge dosis paracetamol de functionele uitkomst van patiënten met een beroerte en een lichaamstemperatuur van 37,0°C of hoger. Dit effect werd echter gevonden in een subgroepanalyse en dient daarom nader te worden onderzocht. Recentelijk is het gerandomiseerde onderzoek PAIS 2 gestart. Hierin wordt het effect bestudeerd van behandeling met een hoge dosis paracetamol op functioneel herstel bij patiënten met een lichaamstemperatuur van 37,0°C of hoger in de acute fase van een beroerte

Dietary intake of antioxidants and risk of Alzheimer disease

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 tota

The Cost of Treatment of Alzheimer's Disease in The Netherlands: A Regression-Based Simulation Model

Objective: To examine the potential economic impact of treatment of Alzheimer's disease. Design: Regression-based simulation estimation of the long term costs of Alzheimer's disease under a number of treatment scenarios. Data from an epidemiological study conducted in Rotterdam, The Netherlands, was used to simulate disease progression. Comparison of the costs and effectiveness experienced by the patients were used to measure the impact of treatment. Patients and intervention: 2 theoretical cohorts of patients with Alzheimer's disease, one of which receives standard treatment, while the other receives a treatment which slows cognitive decline as measured by the Mini-Mental State Examination (MMSE). Main outcome measures and results: Under one of the scenarios examined, the baseline cost of Alzheimer's disease was 97 866 euro (EUR; 1996 values) per patient over 10 years' follow-up; the cost was almost EUR100 000 under all scenarios. Life expectancy following onset was about 4.5 years and MMSE decline was approximately 2 points per year for a typical prevalent (existing) patient and almost twice as much for incident (newly diagnosed) patients (1.82 vs 3.42 points per year, respectively). Slowing the rate of cognitive decline results in a slightly increased life expectancy, with more time being spent at home and less in a nursing home. Total costs (excluding those of therapy) will decrease, but savings will be modest and may well be less than the cost of therapy. Under the same scenario, total savings were EUR1571 per patient which corresponds to an annual break-even cost of just EUR453. Decisions regarding the initiation or termination of therapy will affect both the number of patients treated and the costs and potential savings of treatment. Conclusions: The savings made in treating Alzheimer's disease will almost certainly be small in comparison with total costs and may well be offset by the cost of the treatment itself. Simulation models can be used to estimate the effect of therapy on the costs of care and can be useful tools in clinical decision-making and allocation of resources. These results show the need for further research into the costs and effects of treatment of Alzheimer's disease.Alzheimer's disease, Antidementias, Cost effectiveness, Pharmacoeconomics

Plasma levels of antioxidants are not associated with Alzheimer's disease or cognitive decline.

Item does not contain fulltextAntioxidants prevent oxidative stress that possibly causes neuronal loss in Alzheimer's disease (AD). We examined whether high plasma levels of the antioxidant vitamins A and E were associated with lower prevalence of AD or cognitive decline (CD). We performed a cross-sectional study within the Rotterdam Study. In an univariate model, higher levels of vitamins A and E were significantly associated with lower prevalence of AD. However, when additional adjustments were made for important confounders, such as age, gender and total cholesterol, the relation substantially weakened -- odds ratios per standard deviation increase were 0.87 (95% CI 0.64-1.19) for vitamin A and 0.94 (95% CI 0.60-1.48) for vitamin E. Antioxidants were not related to CD in non-demented subjects. Our findings suggest no association between plasma levels of vitamin A and E and AD or CD

Paracetamol (Acetaminophen) in stroke 2 (PAIS 2) : Protocol for a randomized, placebo-controlled, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke and a body temperature of 36·5°C or above

Rationale: In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37·0°C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1·43; 95% confidence interval: 1·02-1·97). This relation was also found in the patients with a body temperature of 36·5°C or higher (odds ratio 1·31; 95% confidence interval 1·01-1·68). These findings need confirmation. Aim: The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36·5°C or above on functional outcome. Design: The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0·05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36·5°C or above will be included within 12h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. Study outcomes: The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. Discussion: If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide