Nonsteroidal Anti-Inflammatory Drugs and Cognitive Function

Karplus, Theresa M.

doi:10.2165/00002018-199819060-00001

Cited by 27 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, it is conceivable that cognitive side-effects could have been identified as conversion to AD rather than an adverse event, so the absence of a clear difference between rofecoxib and placebo for reported NSAID-type CNS adverse events is inconclusive. Some studies which were specifically designed to assess cognition in normal elderly subjects receiving NSAIDs did find evidence for detrimental effects [34], although as yet no adequately powered randomized controlled trial has been performed to investigate this.…”

Section: Discussionmentioning

confidence: 99%

Rofecoxib in Patients with Mild Cognitive Impairment: Further Analyses of Data from a Randomized, Double-Blind, Trial

Aisen

Thal²,

Ferris³

et al. 2008

CAR

View full text Add to dashboard Cite

A recent clinical trial in patients with Mild Cognitive Impairment (MCI) found an increased rate of possible or probable Alzheimer's disease (AD) diagnoses in patients assigned to rofecoxib compared to placebo. This unexpected finding was difficult to interpret due to methodological issues and a lack of confirmation on secondary endpoints, as well as a lack of confirmation in trials in related populations. We performed additional post hoc analyses to explore explanations for the finding based on possible neuropathological, cardiovascular/cerebrovascular, or cognitive effects of rofecoxib. 1) Neuropathological hypothesis: Of the 189 incident cases of possible or probable AD, 154 were probable AD. In probable AD patients, the treatment hazard ratio was reduced compared to the primary analysis -- a concordant finding would have strengthened a conclusion that rofecoxib accelerated the underlying neuropathology of AD. The treatment hazard ratio was increased in the remaining 35 patients with less certain diagnoses, but there was no single predominant reason for the reduced certainty of diagnosis. 2) Cardiovascular hypothesis: Neither cardiovascular risk status nor mean arterial blood pressure had an overall effect on AD diagnosis or modified the treatment difference. 3) Cognitive side-effects hypothesis: The percentages of patients with non-specific NSAID-type central nervous system adverse events were similar between the treatment groups. In summary, the present analyses are limited by their post hoc nature but provided little support for any of the possible explanations explored. The significance of the observation that rofecoxib increased the rate of conversion from MCI to AD remains uncertain.

show abstract

Section: Discussionmentioning

confidence: 99%

Rofecoxib in Patients with Mild Cognitive Impairment: Further Analyses of Data from a Randomized, Double-Blind, Trial

Aisen

Thal²,

Ferris³

et al. 2008

CAR

View full text Add to dashboard Cite

show abstract

“…A reduced prevalence of Alzheimer's disease has been found among patients with arthritis (McGeer et al, 1996). A reduced risk of Alzheimer's disease has also been observed among users of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) (Stewart et al, 1997;Karplus and Saag, 1998). A clinical study with indomethacin showed some sign for arrest in decline of mental function of treated Alzheimer patients (Rogers et al, 1993) and presently several clinical trials with anti-inflammatory drugs are ongoing.…”

Section: Anti-inflammatory Drugsmentioning

confidence: 99%

Neuroprotection in alzheimer’s disease — new strategies for treatment

Nordberg

2000

neurotox res

View full text Add to dashboard Cite

Alzheimer's disease is the most common dementia disorder characterized by multiple pathological changes in the brain leading to a progressive memory loss and other cognitive symptoms producing occupational and social disabilities. Although a great deal of progress has been made in recent years in further understanding the genetic aberrations and patho-physiological processes of Alzheimer's disease there is still no cure of the disease. The transmitter replacement therapy is so far the most explored therapy. Three cholinesterase inhibitors have so far been approved and presently in clinical use in many countries. Although the cholinesterase inhibitors generally appear to produce symptomatic effects with palliative effect on existing cognitive disturbances recent data suggest that they also may have effect on progression of the disease including possible neuroprotective effects. Possible interactions between Abeta and cholinergic neurotransmission may exist. Treatment of cells with Abeta causes decreased cholinergic activity. Pretreatment of PC12 cells with cholinesterase inhibitors such as tacrine and donepezil in clinical relevant concentrations can attenuate Abeta (25-35) toxicity through mechanisms which may be mediated via nicotinic receptors. Estrogen has been shown to protect against Abeta toxicity in different cell lines and also to reduce the formation of Abeta. Its mechanism for the neuroprotective effect is however not fully clarified. A potentiation of the clinical effect of cholinesterase inhibitors in Alzheimer patients has been given together with estrogen. Experimental data suggest that the neuroprotective effect of estrogen as studied in PC12 cells was mediated at least partly via the alpha(7) nicotinic receptor. Treatment with Abeta in nanomolar concentrations for 7 days in PC12 cells significantly decreased the number of nicotinic receptor binding sites and mRNA levels. The effects by Abeta on nicotinic receptors are prevented by nicotine pretreatment. The finding suggests a possible link between Abeta and nicotinic receptor deficits in Alzheimer patients in the early course of the disease.

show abstract

“…A Swedish population-based study on individuals 80 years old or more revealed users of high-dose (>500 mg/day) aspirin had significantly lower prevalence of Alzheimer's dementia whereas users of 75 mg daily dose had only numerical but insignificant reduction of Alzheimer's dementia, even after correction of stroke, transient ischemic attack, myocardial infarction, angina pectoris, and congestive heart failure [15]. In some studies examining dosage effects, elderly persons who took high-dose NSAIDs got poorer memory and decline faster than those taking low doses [26]. Another case control study involving subjects with average age of 81 disclosed that not only a high-dose (>1000 mg/day) anti-inflammatory action of aspirin but also low-dose antiplatelet action (<500 mg/day) is protective against Alzheimer's dementia [9].…”

Section: Discussionmentioning

confidence: 99%

Mean Daily Dosage of Aspirin and the Risk of Incident Alzheimer’s Dementia in Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study in Taiwan

Chang

Horng

Hsu

et al. 2016

Journal of Diabetes Research

View full text Add to dashboard Cite

Background. Type 2 diabetes mellitus patients are known to have higher risk of developing dementia while aspirin use has been shown to prevent incident dementia. This study was conducted to evaluate the potential benefits of aspirin use on dementia in patients with type 2 diabetes mellitus and identify the appropriate dosage of aspirin that provides the most benefit. Method. A Taiwan nationwide, population-based retrospective 8-year study was employed to analyze the association between the use of aspirin and incidence of dementia including Alzheimer's disease and non-Alzheimer's dementia using multivariate Cox-proportional hazards regression model and adjusting for several potential confounders. Results. Regular aspirin use in mean daily dosage of within 40 mg was associated with a decreased risk of developing incident Alzheimer's dementia in patients with type 2 diabetes mellitus (adjusted HR of 0.51 with 95% CI of 0.27–0.97, p value 0.041). Conclusion. A mean daily dosage of aspirin use within 40 mg might decrease the risk of developing Alzheimer's disease in patients with type 2 diabetes mellitus.

show abstract

Nonsteroidal Anti-Inflammatory Drugs and Cognitive Function

Cited by 27 publications

References 29 publications

Rofecoxib in Patients with Mild Cognitive Impairment: Further Analyses of Data from a Randomized, Double-Blind, Trial

Rofecoxib in Patients with Mild Cognitive Impairment: Further Analyses of Data from a Randomized, Double-Blind, Trial

Neuroprotection in alzheimer’s disease — new strategies for treatment

Mean Daily Dosage of Aspirin and the Risk of Incident Alzheimer’s Dementia in Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study in Taiwan

Contact Info

Product

Resources

About