NSAIDs May Pose Greater Heart Risks Than Colchicine in Gout

 Your competent? doctor knows precisely what to do with colchicine for your recovery. Right?

colchicine (27 posts to December 2011)

And knows about the association of gout with dementia?

Your doctor has a lot of explaining to do. All this other information.

Ask your doctor to compare this research for the best course of action.

Gout may lessen Alzheimer risk March 2015

Study finds no association between gout and neurodegenerative diseases in the general population March 2023

 

Gout unveiled as surprising culprit in neurodegenerative diseases May 2023

The latest here:

NSAIDs May Pose Greater Heart Risks Than Colchicine in Gout

TOPLINE:

In patients with gout starting allopurinol as a long-term urate-lowering therapy, the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a higher risk for major adverse cardiovascular events (MACEs) than the use of colchicine or no prophylaxis.

METHODOLOGY:

• Researchers followed a target trial framework to emulate a randomized clinical trial using data from administrative databases in British Columbia, Canada, to compare the cardiovascular safety of the prophylactic use of NSAIDs vs colchicine in patients with gout who started allopurinol between 1995 and 2022.
• They included 9060 patients who were prescribed NSAIDs (mean age, 60.9 years; 83.5% men) who were propensity score-matched with 9060 patients prescribed colchicine on the same day as allopurinol.
• The primary outcome was MACE, a composite of myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes included the individual components of MACE and all-cause mortality.
• Sensitivity analyses were also conducted with follow-up truncated after 3 months or 6 months and using inverse probability treatment weighting.
• Additionally, the cardiovascular safety of NSAIDs and colchicine was compared with that of no prophylaxis after propensity matching.

TAKEAWAY:

• The risk for MACE was higher in patients using NSAIDs than in those using colchicine (hazard ratio [HR], 1.56; 95% CI, 1.11-2.17). Findings were consistent in sensitivity analyses.
• The use of NSAIDs was associated with significantly higher risks for cardiovascular death (HR, 2.50; 95% CI, 1.14-5.26) and all-cause mortality (HR, 2.00; 95% CI, 1.19-3.45) than the use of colchicine.
• Compared with no prophylaxis, the use of NSAIDs was associated with a 50% higher risk for MACE (HR, 1.50; 95% CI, 1.17-1.91) and a 93% higher risk for myocardial infarction (HR, 1.93; 95% CI, 1.35-2.75), whereas the use of colchicine was not associated with risk for MACE or its individual components.

IN PRACTICE:

“The findings of this present study have the potential to impact clinical care as well as current guidelines, as they highlight the real potential dangers of NSAID use, even short-term, among patients with gout and provide additional evidence in support of colchicine as the preferred paradoxical gout flare prophylaxis agent,” the authors wrote.

SOURCE:

This study was led by Chio Yokose, MD, MSc, Massachusetts General Hospital, Boston. It was published online on May 26, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

The risk for residual confounding factors remained owing to the observational nature of this study. Data on key cardiovascular risk factors such as use of tobacco, BMI, or lipid panel were unavailable. Cardiovascular risk associated with different types of NSAID was not analyzed.

DISCLOSURES:

Some authors reported receiving support from the National Institutes of Health and the Canadian Institutes of Health Research. Several authors reported receiving personal fees, consulting fees, royalties, and grants, and having board positions and other financial ties with multiple pharmaceutical and healthcare companies.

Common Medications Tied to Older Age at Onset of Parkinson Disease

 With your risk of Parkinsons is your competent? doctor up-to-date on all things that could prevent Parkinsons? 

Parkinson’s Disease May Have Link to Stroke March 2017 

Common Medications Tied to Older Age at Onset of Parkinson Disease

Exposures to adrenergic blockers, statins, and NSAIDs were the strongest independent predictors of older Parkinson disease age at onset.

HealthDay News — Multiple common medications are associated with a considerable delay of Parkinson disease (PD) symptom onset, according to a study published online March 6 in the Journal of Neurology.

Camille Malatt, M.D., from the Cedars-Sinai Medical Center in Los Angeles, and colleagues evaluated the association of treatment with antihypertensives, nonsteroidal anti-inflammatories (NSAIDs), and statins, as well as smoking and family history of PD with age at onset (AAO) of clinical symptoms. Analysis included data from 1,201 initial encounters.

The researchers found that exposure to all studied medications showed a strong correlation with older PD AAO. Smoking and family history, however, correlated with younger AAO. Exposures to adrenergic blockers (AB; β = 5.7), statins (β = 5.6), and NSAIDs (β = 4.1) were the strongest independent predictors of older PD AAO. The largest average delay of PD AAO (at 72.3 ± 10.1 years) was seen among patients who were started on AB prior to onset of PD symptoms, which was almost 10 years later versus those not on AB (62.7 ± 10.7 years) or those who started taking AB after onset of symptoms (63.0 ± 10.6 years).

“The medications we studied have common features that may explain their effect on Parkinson disease, including the ability to control inflammation,” senior author Michele Tagliati, M.D., also from Cedars-Sinai, said in a statement. “This research suggests that the medications studied also help control the cellular stress response and brain inflammation, which may have a prominent role in delaying the development of Parkinson disease.”

Several authors disclosed ties to industry.

Abstract/Full Text (subscription or payment may be required)

Long-Term Use of NSAIDs Linked to Lower Dementia Risk

 Your competent? doctor can weigh in on this, considering all this other information.

Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies

Risk of serious NSAID‐related gastrointestinal events during long‐term exposure: a systematic review

Risk of Alzheimer's disease and duration of NSAID use

NSAID exposure and risk of nonunion: a meta-analysis of case–control and cohort studies

The latest here:

Long-Term Use of NSAIDs Linked to Lower Dementia Risk

      Could low-grade inflammation play a role in Alzheimer's and dementia?

by Judy George, Deputy Managing Editor, MedPage Today March 7, 2025

Key Takeaways

• Long-term use of NSAIDs was linked to a lower risk of dementia over 14.5 years of follow-up.
• NSAIDs without known amyloid-beta effects showed a stronger protective association than others.
• Cumulative NSAID doses showed no association with dementia risk.

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) was tied to a decreased risk of dementia, data from the prospective Rotterdam Study showed.

Over an average follow-up of 14.5 years, use of NSAIDs for 24 months or longer was associated with a 12% lower risk of dementia compared with non-use (HR 0.88, 95% CI 0.84-0.91), reported M. Arfan Ikram, MD, PhD, of Erasmus University in Rotterdam, the Netherlands, and co-authors.

The cumulative dose of NSAIDs, however, was not associated with decreased dementia risk, Ikram and colleagues noted in the Journal of the American Geriatrics Society.

The findings could not be explained by the amyloid-lowering properties of specific NSAIDs, the researchers said. Associations were stronger for long-term use of NSAIDs without known effects on amyloid-beta (HR 0.79, 95% CI 0.74-0.85) compared with amyloid-lowering NSAIDs (HR 0.89, 95% CI 0.85-0.93).

For people who used NSAIDs for less than 1 month, dementia risk was slightly elevated (HR 1.04, 95% CI 1.02-1.07), as it was for people who used NSAIDs for 1 month to 24 months (HR 1.04, 95% CI 1.02-1.06).

The findings provide important insights into the relationship between inflammation and dementia risk, suggesting that prolonged, rather than intensive, exposure to anti-inflammatory medication may hold potential for dementia prevention, the researchers noted.

There's a strong hypothesis that inflammation plays a role in the dementia process and in Alzheimer's disease, Ikram pointed out.

"This evidence comes from genetic and animal model studies, as well as some limited studies in clinical patients," he told MedPage Today.

"The idea is that low-grade inflammation contributes to brain damage -- and may also be a result of brain damage due to other detrimental causes like amyloid deposition or arteriolosclerosis," he said. "This may induce a vicious cycle of various pathological processes enhancing and maintaining each other."

The Rotterdam Study findings "suggest the inflammatory process in dementia may be very low-grade and protracted over a long period of time," especially since high doses of NSAIDs over a short time frame didn't reduce dementia risk, Ikram observed. "This makes sense: dementia has a very long preclinical phase during which the pathology slowly accumulates," he said.

Other studies have identified relationships between anti-inflammatory agents and dementia. A meta-analysis showed a decreased dementia risk with NSAIDs in observational studies, but clinical trials -- which typically assess NSAID use over much shorter time frames -- have not.

Ikram and colleagues followed 11,745 participants in the population-based Rotterdam Study who were dementia-free at baseline. More than half (59.5%) were women, and mean age was 66.

The researchers used pharmacy dispensing records to determine cumulative duration and dose of NSAIDs starting in 1991. They defined four categories of cumulative use: non-use, short-term use (under 1 month), intermediate-term use (1 to 24 months), and long-term use (over 24 months).

Models were adjusted for lifestyle factors, comorbidities, and co-medication use. The researchers repeated this analysis after stratifying NSAIDs by their previously established amyloid-beta-lowering properties.

The study's main limitation was its observational nature, Ikram noted. "There is a reason why some individuals did versus did not take NSAIDs. These reasons may include arthritis, pain, or other inflammatory conditions," he said.

"It is impossible to fully adjust for the effect of these other conditions," he acknowledged. "If these other conditions are in any way linked to dementia, it may distort our findings. However, the fact that we found a lower risk of dementia in users compared to non-users indicates that any such distortion may have been limited."

The findings are also insufficient to start advising people to take NSAIDs for dementia, Ikram emphasized.

"Further evidence from similar studies or clinical trials is needed, complemented with proper risk-benefit analyses and a proper assessment on how any use of NSAIDs may or may not outweigh side effects or impact on other bodily functions," he noted.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission; and the Municipality of Rotterdam.

Ikram and co-authors reported no conflicts of interest.

Primary Source

Journal of the American Geriatrics Society

Source Reference: vom Hofe I, et al "Long-term exposure to non-steroidal anti-inflammatory medication in relation to dementia risk" J Am Geriatr Soc 2025; DOI: 10.1111/jgs.19411.

Long-Term NSAID Use Linked to Lower Dementia Risk

Be aware of these problems:

What are symptoms of too much ibuprofen long-term?
Long-term effects:

impaired hearing. kidney and liver damage. bleeding in the stomach and bowels. increased risk of heart attack. 

The main types of NSAIDs include:

• ibuprofen.
• naproxen.
• diclofenac.
• celecoxib.
• mefenamic acid.
• etoricoxib.
• indomethacin.
• aspirin for pain relief (low-dose aspirin is not normally considered to be an NSAID)

Long-Term NSAID Use Linked to Lower Dementia Risk

Summary: A new study finds that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of developing dementia. Researchers followed 11,745 adults over 14.5 years and found that those who used NSAIDs long-term had a 12% reduced dementia risk.

However, short- and intermediate-term NSAID use did not provide the same benefit, nor was the total cumulative dose linked to risk reduction. These findings suggest that sustained anti-inflammatory effects may play a role in protecting against dementia.

Key Facts

• Long-Term NSAID Use: Associated with a 12% lower risk of dementia.
• Short-Term Use: No significant protective effect was observed.
• Anti-Inflammatory Role: Findings support inflammation’s role in dementia progression.

Source: Wiley

Past research has suggested that inflammation may contribute to the development and progression of dementia and that non-steroidal anti-inflammatory (NSAID) medications may help protect against dementia due to their anti-inflammatory effects.

Long-term NSAID use was associated with a 12% reduced risk of developing dementia. Short- and intermediate-term use did not provide benefits. Credit: Neuroscience News

A new large prospective study published in the Journal of the American Geriatrics Society provides additional evidence, showing that long-term NSAID use is linked to a decreased risk of developing dementia.

In the population-based study of 11,745 adults with an average follow-up of 14.5 years, 9,520 participants had used NSAIDs at any given time, and 2,091 participants developed dementia. Long-term NSAID use was associated with a 12% reduced risk of developing dementia. Short- and intermediate-term use did not provide benefits.

Also, the cumulative dose of NSAIDs was not associated with decreased dementia risk.

The findings suggest that prolonged, rather than intensive, use of anti-inflammatory medications may help protect against dementia.

“Our study provides evidence on possible preventive effects of anti-inflammatory medication against the dementia process.

“There is a need for more studies to further consolidate this evidence and possibly develop preventive strategies,” said corresponding author M. Arfan Ikram, MSc, MD, PhD, of Erasmus MC University Medical Center Rotterdam, in the Netherlands.

About this neuropharmacology and dementia research news

Author: Sara Henning-Stout
Source: Wiley
Contact: Sara Henning-Stout – Wiley
Image: The image is credited to Neuroscience News

Original Research: The findings will appear in Journal of the American Geriatrics Society

Are aspirin and other non-steroidal anti-inflammatory drugs effective for preventing dementia?

Oh well, I've been doing 325 for 20 years with no problems. Will have to keep doing my other prevention items.

Are aspirin and other non-steroidal anti-inflammatory drugs effective for preventing dementia? 

Feb 17, 2021 - McMaster University -

The Bottom Line

• Annually, there are around 10 million new cases of dementia worldwide. 
• At present, research shows that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)—such as celecoxib, naproxen, and rofecoxib—may not be effective for dementia prevention, but may come with an increased risk of negative side effects. 
• Thinking of taking aspirin or another NSAID for dementia prevention or using them already? Speak with your health care provider about the potential risks and apparent lack of benefit.  

Every three seconds, a new person is diagnosed with dementia, somewhere in the world (1;2). This translates to approximately 10 million new cases of dementia every year (3). The large increase in cases is directly related to there being no known cure or effective prevention strategies at this time.

In recent years, research has started to focus on the role of inflammation as a cause of dementia, as well as therapies to reduce and control inflammation. These therapies include non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, celecoxib (Celebrex), naproxen (Aleve or Anaprox), and rofecoxib (Vioxx) (4). Aspirin and naproxen are over-the-counter medications that may already be in your kitchen cabinet, while celecoxib requires a prescription from a doctor. Use of all three comes with potential health risks. Aspirin has been shown to increase the risk of major bleeding in people without cardiovascular disease, while oral NSAIDs—such as celecoxib and naproxen—are linked to an increased risk of heart attack at varying doses and lengths of use (5;6). Interestingly, rofecoxib has been removed from the market over safety concerns, but this was a voluntary withdrawal initiated by its own manufactures (7).

Confused by the desire to prevent dementia but not wanting to put yourself at an increased risk for other negative consequences? Let’s take a closer look at a recent systematic review evaluating the effectiveness and safety of NSAID use for dementia prevention (4).

What the research tells us

Overall, the available evidence doesn’t support the use of aspirin or other NSAIDs to prevent dementia.

More specifically, the review found that healthy older adults (no history of dementia, heart disease or physical disability) who take low-dose aspirin (100 mg per day) do not reduce their risk for developing dementia, compared to those taking a placebo. Taking aspirin also does not make a difference in the ability to perform activities of daily living independently. However, those who take aspirin are 17% to 60% more likely to experience major bleeding, and 1% to 28% more likely to die. Although these results are based on one study, the study included over 19,000 participants and the evidence was rated as being of high certainty. This means it is unlikely new studies, if conducted, would change this finding. The authors even noted that due to the risks and lack of effects, we aren’t likely to see more studies on low-dose aspirin and dementia prevention.

What about other NSAIDs?

The results for other NSAIDs are also based on one study each. In cognitively healthy older adults who have a family history of Alzheimer's disease, celecoxib (200 mg twice per day) and naproxen (220 mg twice per day) were not found to reduce the incidence of Alzheimer's disease or increase the risk of stroke, heart attack, or death compared to placebo. Celecoxib (200 mg or 400 mg per day) also did not improve cognition in older adults with age-related memory loss, but may increase the risk of gastrointestinal issues such as nausea, stomach pain, and conditions related to the lining of the stomach being inflamed. Finally, rofecoxib (25 mg once per day) may actually increase the risk of transitioning to a diagnosis of Alzheimer's disease among those with mild cognitive impairment, as well as increase gastrointestinal issues compared to placebo. It should be noted that all the studies included in the review were stopped early due to safety concerns and that the evidence for non-aspirin NSAIDs was rated as being of moderate to low certainty. This means there is a chance that future studies, which take into consideration safety issues, may find different results (4).

Speak with your health care provider before starting or stopping any prescribed or over-the-counter medications in your efforts to hold off dementia. Although there are no foolproof strategies for dementia prevention, there are non-drug related tactics that we can use to help boost our cognitive health. These include combined physical activity and brain training for people with or without mild cognitive impairment, and visual art therapy and computerized brain games for people with mild cognitive impairment (8-10).

Diclofenac reduces the risk of Alzheimer’s disease: a pilot analysis of NSAIDs in two US veteran populations

But better than coffee? WHOM do we got to to get that simple question answered?

Maybe you want to read these two negative articles on diclofenac:

Major Study Points to Cardiac and Stroke Risks of One of World’s Biggest Drugs

EU regulator advises caution on painkiller diclofenac

 

Your chances of getting dementia.

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

5. Parkinson’s Disease May Have Link to Stroke March 2017 

Coffee May Lower Your Risk of Dementia Feb. 2013 

And this: Coffee's Phenylindanes Fight Alzheimer's Plaque 

 

The latest here:

Diclofenac reduces the risk of Alzheimer’s disease: a pilot analysis of NSAIDs in two US veteran populations 

Show all authors

Olaf Stuve, Rick A. Weideman, Danni M. McMahan, ...

First Published June 25, 2020 Research Article

https://doi.org/10.1177/1756286420935676

Article information

Abstract

Background:

Our aim was to determine whether specific nonsteroidal anti-inflammatory (NSAID) agents are associated with a decreased frequency of Alzheimer’s disease (AD).

Materials and methods:

Days of drug exposure were determined for diclofenac, etodolac, and naproxen using US Department of Veterans Affairs (VA) pharmacy transaction records, combined from two separate VA sites. AD diagnosis was established by the International Classification of Diseases, ninth revision (ICD-9)/ICD-10 diagnostic codes and the use of AD medications. Cox regression survival analysis was used to evaluate the association between AD frequency and NSAID exposure over time. Age at the end of the study and the medication-based disease burden index (a comorbidity index) were used as covariates.

Results:

Frequency of AD was significantly lower in the diclofenac group (4/1431, 0.28%) compared with etodolac (328/14,646, 2.24%), and naproxen (202/12,203, 1.66%). For regression analyses, naproxen was chosen as the comparator drug, since it has been shown to have no effect on the development of AD. Compared with naproxen, etodolac had no effect on the development of AD, hazard ratio (HR) 1.00 [95% confidence interval (CI): 0.84–1.20, p = 0.95]. In contrast, diclofenac had a significantly lower HR of AD compared with naproxen, HR 0.25 (95% CI: 0.09–0.68, p <0.01). After site effects were controlled for, age at end of the study (HR = 1.08, 95% CI: 1.07–1.09, p <0.001) was also found to influence the development of AD, and the medication-based disease burden index was a strong predictor for AD, HR 5.17 (95% CI: 4.60–5.81) indicating that as comorbidities increase, the risk for AD increases very significantly.

Conclusion:

Diclofenac, which has been shown to have active transport into the central nervous system, and which has been shown to lower amyloid beta and interleukin 1 beta, is associated with a significantly lower frequency of AD compared with etodolac and naproxen. These results are compelling, and parallel animal studies of the closely related fenamate NSAID drug class.

Keywords Alzheimer’s disease, diclofenac, naproxen, etodolac

Introduction

Alzheimer’s disease (AD) is a chronic, progressive, and irreversible age-related neurodegenerative disorder characterized by cognitive and memory impairment. It is the most common cause of dementia in older adults. It was estimated in 2015 that 44 million people were living with AD worldwide, and this number is expected to double by 2050.¹ More than 95% of people with AD have sporadic or late-onset AD, a multi-factorial disorder with environmental factors and genetic predisposition contributing to the pathology.¹
The pathophysiology of AD is characterized by abnormal extracellular accumulation of amyloid-β peptide (Aβ) in amyloid plaques, and abnormal intracellular accumulation of tau protein in neurofibrillary tangles (NFTs).¹ Several theories are published regarding the AD pathogenesis. The amyloid cascade theory proposes that the accumulation of Aβ plaques in the brain is the primary pathogenic event.^2–4 The tau hypothesis proposes that tau hyperphosphorylation is the underlying etiology.^5–9 The cholinergic theory suggests AD is associated with a reduction in the choline acetyltransferase activity and acetylcholine levels in specific areas of the brain such as the cerebral cortex.^10,11 These proposed disease mechanisms result in a loss of synaptic function, mitochondrial damage, activation of microglia, and neuronal death.¹² Neuroinflammation is mediated primarily by microglia cells, and neuroinflammation contributes to AD pathogenesis.^13–15 Microglia activation has a dual effect on AD progression: it leads to (a) a reduction of Aβ accumulation by increasing phagocytosis, clearance, and degradation, and (b) the release of pro-inflammatory cytokines, and triggers the inflammatory cascade that contributes to neuronal damage and death.¹²
Interleukin-1β (IL-1β) is an important pro-inflammatory cytokine in the brain.^16,17 It is generated by the cytosolic nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes, where nucleotide-binding oligomerization-domain-like receptors (NLRs) are engaged, resulting in increased IL-1β release.¹⁸ Evidence is growing that IL-1β plays a central role in AD progression.^19,20 The NLRP3-IL-1β is synthesized and released from activated microglia and astrocytes. One study has documented that IL-1β interferes with glutamate reuptake in astrocytes, potentially leading to glutamate toxicity.²¹ Another study showed that soluble oligomeric Aβ increases the formation of mature IL-1β in microglia.¹² Over-expression of IL-1β release from microglia and astrocytes surrounding Aβ plaques occurs in the AD brain.^22,23 Several studies have demonstrated that the over-expression of IL-1β exacerbates tau phosphorylation and NFT development.^24–26 Subsequently, synaptic plasticity leads to disruption of the brain’s learning and memory processes.¹² Finally, the blockade or neutralization of IL-1β in an AD mouse model was protective against cognitive defects, decreased tau pathology and the synthesis of Aβ.¹²
Early studies of AD included the use of non-steroidal anti-inflammatory drugs (NSAIDs).²⁷ In a Cochrane NSAID and Alzheimer’s review, these prior studies in AD patients compared aspirin and NSAID exposures to patients who had not received them and the results from these studies were equivocal.²⁷ Vlad and colleagues, however, concluded that over time, ibuprofen and NSAIDs as a group have a protective effect but that other individual NSAIDs did not consistently exhibit this effect, perhaps due to ‘small numbers of users.’²⁸ In addition, many studies do not specify which NSAIDs were used, although the effects of indomethacin,^29,30 celecoxib,³¹ naproxen^32–35 ibuprofen,³⁶ and naproxen have been studied. Of these, only indomethacin²⁹ and ibuprofen²⁸ were associated with less cognitive decline in AD. A recent meta-analysis of 16 NSAID cohort studies³⁷ reported a decreased likelihood of AD with the pooled data of 236,022 patients; however, individual NSAIDs had no effect when stratified by NSAID type.
It is important to note that there are eight different chemical classes of NSAIDs³⁸ and this may have a significant effect on their ability to interrupt the AD process. In 2006, Joo and colleagues³⁹ found a neuroprotective effect of mefenamic acid administration in in vitro and in vivo models. In 2016, Daniels and colleagues⁴⁰ also detected a protective effect of the fenamate class of NSAIDs against AD and they hypothesized that it was due to inhibition of IL-1β release from the NLRP3 inflammasome in immortalized mouse bone-marrow-derived macrophages. In the initial in vitro phase of their study, the fenamates (flufenamic acid, mefenamic acid and meclofenamic acid) were more effective at inhibiting IL-1β release than celecoxib or ibuprofen, which had no effect on IL-1β release.⁴⁰ In contrast, diclofenac was associated with a modest but significant reduction in IL-1β release. In the second phase of their study, Daniels and colleagues showed that the fenamate drug class also prevented Aβ-induced memory deficits in rats,⁴⁰ and it decreased AD-related neuroinflammation in three AD-transgenic (TG) mice that expressed the presenilin mutation PS1M146V,⁴¹ the mutant amyloid precursor protein APPSwe,⁴² and a transgene of the human mutant P301 tau gene (tauP301L transgene).⁴³ These animals develop a progressive neuropathological phenotype with increasing age that includes Aβ plaques and neurofibrillary tangles.⁴⁴ Fenamate treatment was associated with decreased IL-1β expression and microglial activation in AD mice equivalent to levels in wild-type mice.⁴⁰
Very recently, Rivers-Auty and colleagues, evaluating fenamate NSAIDs, reviewed diclofenac use in a database of patients with Alzheimer’s disease and found that it reduced cognitive deterioration.⁴⁵ At this time, however, this finding has only been presented in abstract form.
The purpose of this retrospective cohort study was to determine whether chronic diclofenac use is associated with a lower frequency of AD in a veteran population compared with chronic use of etodolac or naproxen.

Can aspirin treat Alzheimer's?

But what about this from April, 2018? Demand your doctor find out which one is better. You do expect your doctor to know this medical stuff down cold, don't you? Or are you giving them a pass just like you gave them a pass on not getting you 100% recovered?

Can You Take Aspirin and Ibuprofen Together? - Healthline

A dangerous combination. Both aspirin and ibuprofen belong to a drug class called nonsteroidal anti-inflammatory drugs (NSAIDs). They have similar side effects, and taking them together increases your risk of these side effects. Aspirin and ibuprofen can cause stomach bleeding, especially if you take too much.

The Common Painkiller That Prevents Alzheimer’s Disease - Ibuprofen April 2018

Can aspirin treat Alzheimer's?

A regimen of low-dose aspirin potentially may reduce plaques in the brain, which will reduce Alzheimer's disease pathology and protect memory, according to neurological researchers at Rush University Medical Center, who published the results of their study today in the July issue of The Journal of Neuroscience.

"The results of our study identifies a possible new role for one of the most widely used, common, over-the-counter medications in the world," said Kalipada Pahan, Ph.D., the study's senior author and lead research investigator, who also is the Floyd A. Davis, MD, Endowed Chair of Neurology and professor of neurological sciences, biochemistry and pharmacology in Rush Medical College.
Alzheimer's disease is a fatal form of dementia that affects up to 1 in 10 Americans age 65 or older. To date, the FDA has approved very few drugs for the treatment of Alzheimer's disease-related dementia and the medications that exist can only provide limited symptomatic relief.
The exact cause of Alzheimer's disease progression is unknown; however, poor disposal of the toxic protein amyloid beta in the brain is a leading mechanism in dementia and memory loss.
Activating the cellular machinery responsible for removing waste from the brain therefore has emerged as a promising strategy for slowing Alzheimer's disease.
Amyloid beta forms clumps called amyloid plaques, which harm connections between nerve cells and are one of the major signs of Alzheimer's disease. Building on previous studies demonstrating a link between aspirin and reduced risk and prevalence of Alzheimer's disease,
Pahan and his colleagues were able to show that aspirin decreases amyloid plaque pathology in mice by stimulating lysosomes—the component of animal cells that help clear cellular debris.

Aspirin treatment reduces amyloid beta burden in the hippocampus of 5XFAD mouse model of AD. Credit: Chandra et al., JNeurosci (2018)

"Understanding how plaques are cleared is important to developing effective drugs that stop the progression of Alzheimer's disease," said Pahan.
A protein called TFEB is considered the master regulator of waste removal. The researchers gave aspirin orally for a month to genetically modified mice with Alzheimer's pathology, then evaluated the amount of amyloid plaque in the parts of the brain affected most by Alzheimer's disease.
They found that the aspirin medications augmented TFEB, stimulated lysosomes and decreased amyloid plaque pathology in the mice.
"This research study adds another potential benefit to aspirin's already established uses for pain relief and for the treatment of cardiovascular diseases," said Pahan. "More research needs to be completed, but the findings of our study has major potential implications for the therapeutic use of aspirin in AD and other dementia-related illnesses."

Explore further: New tools could uncover important answers for Alzheimer's researchers

More information: Sujyoti Chandra et al, Aspirin induces Lysosomal biogenesis and attenuates Amyloid plaque pathology in a mouse model of Alzheimer's disease via PPARα, The Journal of Neuroscience (2018). DOI: 10.1523/JNEUROSCI.0054-18.2018 , dx.doi.org/10.1523/JNEUROSCI.0054-18.2018

Journal reference: Journal of Neuroscience
Provided by: Rush University Medical Center

 

Are you taking too much anti-inflammatory medication?

NSAIDs? Aspirin?

Are you taking too much anti-inflammatory medication?

Anti-inflammatory therapy for preventing stroke and other vascular events after ischaemic stroke or transient ischaemic attack

It is just a review of research so nothing useful will come of this for a protocol.

Anti-inflammatory therapy for preventing stroke and other vascular events after ischaemic stroke or transient ischaemic attack

Many pages prior to what I copied here;

Description of the intervention

Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Broadly, they consist of steroids (e.g. glucocorticoids), non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, colchicine, antimetabolite drugs such as methotrexate and azathioprine, and anticytokine agents including TNF-alpha-binding proteins (e.g. infliximab). Mycophenolate is another immune-modulating drug. Each of these types of drug have different pharmacokinetics and pharmacodynamics.

Glucocorticoids

Glucocorticoids are potent anti-inflammatory agents targeting both the early and late phases of inflammation. Glucocorticoids target inflammation through multiple pathways including the decreased activation of neutrophils, macrophages and T-helper cells. They also downregulate the production of multiple cytokines, including IL-1, IL-2, IL-6 and TNF-alpha, through the inhibition of gene transcription. In addition, glucocorticoids inhibit the production of prostanoids through decreased expression of COX-2, and are partly responsible for the upregulation of anti-inflammatory factors, including IL-10 and annexin 1.

Non-steroidal anti-inflammatory drugs

NSAIDs are very commonly used anti-inflammatory medications. They are weak organic acids that are highly metabolised to form an active agent. Their anti-inflammatory activity is primarily as a result of the biosynthesis of prostaglandins; however, they also inhibit chemotaxis, IL-1 production and free-radical formation. NSAIDs also decrease the sensitivity of blood vessels to bradykinin and histamine, as well as decreasing the production of lymphokines from T lymphocytes.

Cyclooxygenase-2 inhibitors

The COX-2 isoenzyme is induced by proinflammatory cytokines (e.g. IL-1ß, TNF-alpha) and endotoxins in response to inflammation, and is responsible for the increased level of prostaglandins during inflammation. By inhibiting this isoenzyme the inflammatory process is downregulated as the production of regulatory cytokines is not inhibited, and B- and T-cell proliferation is reduced.

Colchicine

The anti-inflammatory effect of colchicine is mediated primarily through the inhibition of microtubule assembly. This inhibits inflammasome activation, cell chemotaxis, and the production of leukotrienes and cytokines thus inhibiting inflammation. By inhibiting the inflammasome, colchicine inhibits IL-1ß activation from its precursor, proIL-1ß, thus limiting the inflammatory response. Colchicine is also responsible for inhibiting the expression of IL-1ß, IL-6 and TNF-alpha through the reduced activation of macrophages.

Antimetabolites (e.g. methotrexate, azathioprine)

Different antimetabolite drugs have different mechanisms of action. Methotrexate, an antifolate drug that interferes with DNA replication, exerts its anti-inflammatory action through the inhibition of cytokines. The exact mechanism via which this inhibition occurs remains unknown. Methotrexate is also believed to inhibit lymphocyte proliferation through the inhibition of purine synthesis. Azathioprine, a purine analogue that also inhibits DNA synthesis, inhibits T-cell proliferation through complex genetic interactions leading to a depressed immune response.

Anticytokine drugs

This is a class of recombinant engineered antibodies that interact with the immune system. Within this broad class of immunomodulating agents, different agents target different cytokines involved in the inflammatory pathway. The main targets are TNF-alpha (infliximab, adalimumab), IL-1 antagonism (canakinumab, anakinra) and IL-2 antagonism (daclizumab).

How the intervention might work

Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines the inflammatory pathway may be interrupted at various stages. Non-specific agents, including NSAIDs, COX-2 inhibitors and colchicine, inhibit inflammation through downregulation of prostaglandin synthesis and chemokine modulation. Inflammatory cells, such as neutrophils and mast cells, as well as endothelial cell adhesion molecules, are inhibited, thus impeding the initiation and intensification of inflammation. Using medications such as infliximab, etanercept and adalimumab, which target TNF-alpha (a multifunctional proinflammatory cytokine that may be involved in the development of atherosclerosis), the production of more downstream inflammatory cytokines such as IL-6, as well as the proliferation of leucocytes, may be impeded. TNF-alpha antagonism may also inhibit the earliest stages of atherosclerosis development as this may downregulate smooth muscle proliferation as well as inhibiting the expression of VCAM-1, thus decreasing the adherence of leucocytes to endothelial cells. By targeting IL-6 with agents such as tocilizumab, both membrane-bound and circulating IL-6 receptors may be blocked. This may help minimise endothelial dysfunction and reduce arterial stiffness in addition to minimising the proinflammatory effect of IL-6. IL-1ß is also a promising target. IL-1ß receptor inhibition may reduce leucocyte adhesion in vascular endothelial cells, which leads to procoagulant activity, and serves as a trigger for human vascular smooth muscle cell proliferation. Such agents include canakinumab and anakira. Certain harms may, however, be associated with the use of anti-inflammatory agents. By impeding anti-inflammatory pathways, many anti-inflammatory medications will also affect the overall immune system, leaving recipients of these drugs vulnerable to infection, in particular opportunistic infections, such as systemic fungal infections, and those caused by mycobacteria and other atypical organisms. These infections can be potentially life threatening. Some anti-inflammatory drugs, such as methotrexate and cyclophosphamide, can lead to myelosuppression, causing a decrease in the white cell count and suppression of the immune system. NSAIDs, COX-2 inhibitors and steroids have also been shown to increase the risk of gastrointestinal mucosal injury through the inhibition of prostaglandins. 
More at link.

Duration of Analgesic Use and Risk of Hearing Loss in Women

Luckily, aspirin use does not seem to be a problem with this.
https://academic.oup.com/aje/article-abstract/doi/10.1093/aje/kww154/2661733/Duration-of-Analgesic-Use-and-Risk-of-Hearing-Loss?

Brian M. Lin

Sharon G. Curhan

Molin Wang

Roland Eavey

Konstantina M. Stankovic

Gary C. Curhan

Am J Epidemiol (2016) 1-8.

DOI:

https://doi.org/10.1093/aje/kww154

Published:

14 December 2016

Article history

• Cite
• Share
• Tools

search filter search input

Abstract

Aspirin, nonsteroidal antiinflammatory drugs (NSAID), and acetaminophen are commonly used. Frequent use of analgesics has been associated with a higher risk of hearing loss. However, the association between duration of analgesic use and the risk of hearing loss is unclear. We investigated the relationship between duration of analgesic use and self-reported hearing loss among 55,850 women in the Nurses’ Health Study. Cox proportional hazards regression was used to adjust for potential confounders. During 873,376 person-years of follow-up (1990–2012), longer durations of NSAID use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.10, 95% confidence interval: 1.06, 1.15; P for trend < 0.001) and acetaminophen use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.09, 95% confidence interval: 1.04, 1.14; P for trend < 0.001) were associated with higher risks of hearing loss. Duration of aspirin use was not associated with hearing loss (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.01, 95% confidence interval: 0.97, 1.05; P for trend = 0.35). In this cohort of women, longer durations of NSAID and acetaminophen use were associated with slightly higher risks of hearing loss, but duration of aspirin use was not. Considering the high prevalence of analgesic use, this may be an important modifiable contributor to hearing loss.