ASPIRIN: the best NSAID

Home | Aspirin prevents MI, Cancer & Alzheimer's--a summary--jk | Aspirin-prevents-cancer-heart-attacks-Alzheimer's | Aspirin, various benefits | ASPIRIN: HISTORY & USES | Aspirin reduces cancer Metastasis, survival up 67% | Aspirin: UK study finds major reduction in cancer death | Breast Cancer Aspirin, Harvard Nurses' Study, complete | ALL NON-ASPIRIN NSAIDS INCREASE MI | American Heart Association warns NSAIDs cause MI | Aspirin reduces cancer risk | Aspirin mechanism cancer survival | aspirin & cancer, mechanism, etc. | NAPROXIN CAUSED 50% more CORONARY events than placebo | Reyes Syndrome--PhARMA's attack upon aspirin | Aspirin reduces C-recative Protein (MI reduction) | Alzheimer's Disease Risk Reduced 60% | ASPIRIN COATED SAFER THAN OTHER NSAIDS | More articles on various benefits of ASPIRIN | Understanding thrombi & coagulation | ASPIRIN REDUCES CORONARY THROMBOSIS 51% | ASPIRIN BEFORE BYPASS SURGERY SAVES LIVES | ASPIRIN BEST FOR THOSE WITH BYPASS | HOW ASPIRIN PROTECTS AGAINST COLON CANCER | Aspirin reduces risk of colon cancer 50% | The more you take the lower the risk of colon cancer | VIOXX mechanism (COX-1 & 2) explained | Why COX-2 inhibitors (VIOXX) kill, mechanism explained | VIOXX, brothers, PROFITS: the aspirin alternatives | Prexige works like asprin and VIOXX | WHICH NSAID, IBUPROFIN OR ASPIRIN? | WOMEN BENEFITS, breast cancer and C-sections | ASPIRIN PREVENTS PREGNANCY COMPLICATION | Alzheimer's Drug, Aricpet, avoid | WARFARIN and COUMADIN warnings

Alzheimer's Disease Risk Reduced 60%

RISK OF Alzheimer’s disease (AD) .60% lower on 2-year usage, bottom study shows.  The results are better with high dose since this study failed to eliminate those who took low-dose (85 or 125 mg) aspirin.  The low-dose aspirin will not produce long-term a sufficient anti-inflammatory response, and its cardiovascular effect through lowering thrombi is also0 less.-JK. 

The study below, extremely well designed population study (same-sex twins), showed significant reduction of Alzheimer’s disease (AD) with high dose aspirin, but no benefits for either low dose (85 mg) or other NSAIDs.  

 15 year study on the use of aspirin, other NSADs, and acetaminophen.  The relative risk of Alzheimer’s Disease (AD) was correlated with increase duration of NSID use.  With 2 or more years the risk was 40% with less than 2 years 65%.  No reduction of AD with acetaminophen usage, thus supporting the conjecture that the anti-inflamatory role of the NSADs is protective.    

Neurology,  997; 48: 626-632  published by the American Academy of Neurology

Risk of Alzheimer's disease and duration of NSAID use

  1. Abstract

Article abstract-In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications. Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.84) compared with 0.65 (95% CI: 0.33-1.29)   of NSAID use. The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of decreasing risk of AD was observed with increasing duration of aspirin use. No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process. 

European Journal of Clinical Pharmacology

Volume 59, Number 4, 313-319, DOI: 10.1007/s00228-003-0618-y

Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged =80 years

Sven E. Nilsson, Boo Johansson, Sanna Takkinen, Stig Berg, Steven Zarit, Gerald McClearn and Arne Melander

 

Abstract

Objective  

It has been reported that aspirin and other non-steroidal anti-inflammatory drugs (NSAID) may protect against dementia of Alzheimer's type and/or vascular dementia. However, co-morbidity and the dose of aspirin may be critical. A major indication for low-dose aspirin is prophylaxis after stroke and transient ischaemic attacks, conditions that may obscure an anti-dementia effect by the drug. Alternatively, low-dose aspirin may be insufficient if the protective effect is due to an anti-inflammatory mechanism. The aim of this study was to assess whether high-dose or low-dose aspirin may protect against Alzheimer's dementia in subjects aged 80 years. For comparison, effects of (other) NSAID, paracetamol and d-propoxyphene were studied.

Methods  

Global, cross-sectional, and longitudinal (1991–2000) epidemiological analyses of clinical, cognitive and drug treatment data on 702 individuals 80 years old or more (351 twin pairs of same sex), all alive at inclusion: mean age 83.9 years (80–99 years). Calculations were made with logistic regression of associations between use of various analgesics and cognitive function, after adjustment for age, gender, and cardiovascular and cerebrovascular diseases.

Results  

Users of high-dose aspirin had significantly lower prevalence of Alzheimer's dementia and better-maintained cognitive function than non-users. There were numerically similar but not significant associations with use of low-dose aspirin and other NSAID. There were no such associations with use of either paracetamol or d-propoxyphene.

Conclusion  

Aspirin might protect against Alzheimer's disease, but controlled trials are warranted.

 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

15 year study on the use of aspirin, other NSADs, and acetaminophen.  The relative risk of Alzheimer’s Disease (AD) was correlated with increase duration of NSID use.  With 2 or more years the risk was 40% with less than 2 years 65%.  No reduction of AD with acetaminophen usage, thus supporting the conjecture that the anti-inflamatory role of the NSADs is protective.    

Neurology,  997; 48: 626-632  published by the American Academy of Neurology

Risk of Alzheimer's disease and duration of NSAID use

  1. Abstract

Article abstract-In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications. Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.84) compared with 0.65 (95% CI: 0.33-1.29)   of NSAID use. The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of decreasing risk of AD was observed with increasing duration of aspirin use. No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process.

 

 

 

 

ALS (Amyotrophic lateral sclerosis) s clinically characterized as an inflammatory process affecting certain parts of the brain.  Aspirin and all NSAIDs block the enzyme cyclooxygenase 2 (COX-2).  Thus it would seems plausible that aspirin would lower risk and increase survival of those with ALS   This lead is supported in studies of transgenic mice expressing a human superoxide dismutase SOD!; however, a search of research has failed to find this lead pursued.   Since  

THE FASEB Journal http://www.fasebj.org/content/17/6/725.full The FASEB Journal. 2003;17:725-727

A therapeutic role for cyclooxygenase-2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis 1

 SPECIFIC AIMS

We report the effects of the preferential cyclooxygenase (COX)-2 inhibitor nimesulide on motor impairment in the G93A superoxide dismutase (SOD1-G93A) mouse model of amyotrophic lateral sclerosis (ALS). Prophylactic dietary supplementation with nimesulide beginning at 7 wk of age resulted in a significant delay in the onset of motor impairment and reduced COX-2-mediated induction of proinflammatory prostaglandin in the cervical spinal cord toward normal/control levels. This evidence provides strong support for the therapeutic use of COX-2 inhibitors in ALS.

PRINCIPAL FINDINGS

1. Motor ability as a function of the therapeutic efficacy of nimesulide
To measure the onset and progression of ALS type symptomatology in SOD1-G93A transgenic mice, we conducted two independent but similar tests of muscle strength, balance, and coordination: the accelerating Rotarod and the grid walking test. We found that SOD1-G93A* transgenic mice fed normal diet exhibited a mean onset of motor impairment at 108 days of age in the Rotarod test (Fig. 1Description: http://www.fasebj.org/icons/ref-arrow.gif A) and 113 days in the grid walking test (Fig. 1BDescription: http://www.fasebj.org/icons/ref-arrow.gif ). However, dietary supplementation with nimesulide imparted a significant delay in the onset of ALS-type symptomatology and preserved motor skill integrity up to 120 days of age in the Rotarod test and 124 days in the grid walking test. After this period of therapeutic delay, motor activity of SOD1-G93A mice fed the nimesulide diet declined to levels similar to that of SOD1-G93A mice fed a normal diet. Wild-type groups displayed optimum performance scores of 180 s (Rotarod) and 0 foot misses (grid walking test) throughout the testing period.

CONCLUSIONS AND SIGNIFICANCE

Increasing anecdotal evidence suggests that, based on anti-inflammatory properties, COX-2 inhibitors may delay neuroinflammation in ALS and be useful in lessening the symptoms of motor dysfunction in this disease. In the present study we provide the first experimental evidence that prophylactic treatment of SOD1-G93A mice with the preferential COX-2 inhibitor nimesulide significantly delays the onset of motor dysfunction in the SOD1-G93A transgenic mice relative to SOD1-G93A mice fed a normal diet. Nimesulide is a preferential COX-2 inhibitor with potent antioxidant properties that we have previously shown to be well tolerated in geriatric patients for periods of > 2 years. The delay of ALS symptomatology in the SOD 1 mutant mice observed here was achieved at tolerable doses of nimesulide (that reached micromolar concentrations in the brain) and resulted in significantly decreased levels of PG-E2 content in the spinal cord. These studies suggest that inhibition of COX-2, which blocks PG-E2 production, may therapeutically delay the onset of motor neuron symptomatology in ALS patients.

In view of the ongoing clinical trial of the selective COX-2 inhibitor Celebrex sponsored by the Northeast ALS consortium, these data provide significant support for the therapeutic application of NSAIDs to ALS. However, nimesulide did not alter the onset of end stage disease (bilateral hind limb paralysis) or the weight loss associated with the SOD1-G93A transgenic mice, suggesting that additional pathophysiologic mechanisms in ALS need to be addressed in order to more comprehensively treat this disease. Further, given the prophylactic nature of this study, it may also be the case that NSAIDS will need to be administered very early in the disease process in order to achieve optimal efficacy, as has been suggested in recent experimental studies with aspirin and creatine. Nonetheless, we think this study provides significant validation for the ongoing trial of Celebrex, and clearly emphasizes the need for further study of these compounds in inflammatory neurodegeneration.

If the hypothesis that COX-2 plays an important role in neurodegeneration (see Fig. 3Description: http://www.fasebj.org/icons/ref-arrow.gif ) in ALS is indeed correct, then CNS penetration with selective or preferential COX-2 may be successful in inhibitors altering the clinical progression of ALS in humans. Experimental studies in animal models, cell culture models of ALS-type neurodegeneration, and studies of postmortem ALS brain have all implicated COX-2 as an important therapeutic target in ALS, and our findings with nimesulide further underscore this implication. These studies provide strong support for ongoing clinical studies of COX-2 inhibitors and advocate further exploration of additional NSAID compounds (e.g., mixed COX-1/-2 inhibitors) in the treatment and management of ALS.

 

*The SOD-1 mutation was discovered in familial ALS, and thus lead to the introduction of that mutation in mice--jk.

 

Enter supporting content here

INTERNAL SITE SEARCH ENGINE by Google

Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for any medical advice, diagnosis, and treatment.