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Review
. 2012 Feb 15;2012(2):CD006378.
doi: 10.1002/14651858.CD006378.pub2.

Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease

Darin Jaturapatporn  1 , Mokhtar Gad El Kareem Nasr Isaac, Jenny McCleery, Naji Tabet
Affiliations
Review

Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease

Darin Jaturapatporn et al. Cochrane Database Syst Rev. .

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia. The incidence of AD rises exponentially with age and its prevalence will increase significantly worldwide in the next few decades. Inflammatory processes have been suspected in the pathogenesis of the disease.

Objectives: To review the efficacy and side effects of aspirin, steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of AD, compared to placebo.

Search methods: We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 12 April 2011 using the terms: aspirin OR "cyclooxygenase 2 inhibitor" OR aceclofenac OR acemetacin OR betamethasone OR celecoxib OR cortisone OR deflazacort OR dexamethasone OR dexibruprofen OR dexketoprofen OR diclofenac sodium OR diflunisal OR diflusinal OR etodolac OR etoricoxib OR fenbufen OR fenoprofen OR flurbiprofen OR hydrocortisone OR ibuprofen OR indometacin OR indomethacin OR ketoprofen OR lumiracoxib OR mefenamic OR meloxicam OR methylprednisolone OR nabumetone OR naproxen OR nimesulide OR "anti-inflammatory" OR prednisone OR piroxicam OR sulindac OR tenoxicam OR tiaprofenic acid OR triamcinolone OR NSAIDS OR NSAID. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (including MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries (including national, international and pharmacuetical registries) and grey literature sources.

Selection criteria: All randomised controlled trials assessing the efficacy of aspirin, steroidal and non-steroidal anti-inflammatory drugs in AD.

Data collection and analysis: One author assessed risk of bias of each study and extracted data. A second author verified data selection.

Main results: Our search identified 604 potentially relevant studies. Of these, 14 studies (15 interventions) were RCTs and met our inclusion criteria. The numbers of participants were 352, 138 and 1745 for aspirin, steroid and NSAIDs groups, respectively. One selected study comprised two separate interventions. Interventions assessed in these studies were grouped into four categories: aspirin (three interventions), steroids (one intervention), traditional NSAIDs (six interventions), and selective cyclooxygenase-2 (COX-2) inhibitors (five interventions). All studies were evaluated for internal validity using a risk of bias assessment tool. The risk of bias was low for five studies, high for seven studies, and unclear for two studies.There was no significant improvement in cognitive decline for aspirin, steroid, traditional NSAIDs and selective COX-2 inhibitors. Compared to controls, patients receiving aspirin experienced more bleeding while patients receiving steroid experienced more hyperglycaemia, abnormal lab results and face edema. Patients receiving NSAIDs experienced nausea, vomiting, elevated creatinine, elevated LFT and hypertension. A trend towards higher death rates was observed among patients treated with NSAIDS compared with placebo and this was somewhat higher for selective COX-2 inhibitors than for traditional NSAIDs.

Authors' conclusions: Based on the studies carried out so far, the efficacy of aspirin, steroid and NSAIDs (traditional NSAIDs and COX-2 inhibitors) is not proven. Therefore, these drugs cannot be recommended for the treatment of AD.

PubMed Disclaimer

Conflict of interest statement

All authors declare no conflict of interest in this research project.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Aspirin vs. aspirin avoidance, Outcome 1 Bleeding.
1.2
1.2. Analysis
Comparison 1 Aspirin vs. aspirin avoidance, Outcome 2 Death.
1.3
1.3. Analysis
Comparison 1 Aspirin vs. aspirin avoidance, Outcome 3 Institutionaliation.
2.1
2.1. Analysis
Comparison 2 Steroids vs. placebo, Outcome 1 ADAScog.
2.2
2.2. Analysis
Comparison 2 Steroids vs. placebo, Outcome 2 Confusion.
2.3
2.3. Analysis
Comparison 2 Steroids vs. placebo, Outcome 3 hyperglycemia.
2.4
2.4. Analysis
Comparison 2 Steroids vs. placebo, Outcome 4 Abnormal lab results.
2.5
2.5. Analysis
Comparison 2 Steroids vs. placebo, Outcome 5 Face edema.
3.1
3.1. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 1 Cognition:ADAScog all studies.
3.2
3.2. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 2 Cognition:MMSE all.
3.3
3.3. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 3 CIBIC+.
3.4
3.4. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 4 CDR sum score.
3.5
3.5. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 5 NPI.
3.6
3.6. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 6 Mood/depression.
3.7
3.7. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 7 Clinical global impression: GDS.
3.8
3.8. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 8 Clinical global impression: CGIC and NOSGER 6 months.
3.9
3.9. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 9 Behavioral disturbance.
3.10
3.10. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 10 Activity of daily living.
3.11
3.11. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 11 Quality of life.
3.12
3.12. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 12 Caregiver burden.
3.13
3.13. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 13 Gastrointestinal side effects.
3.14
3.14. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 14 Elevated creatinine.
3.15
3.15. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 15 Elevated liver function test.
3.16
3.16. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 16 Headache.
3.17
3.17. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 17 Psychiatric side effects.
3.18
3.18. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 18 Bleeding.
3.19
3.19. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 19 Heart disease.
3.20
3.20. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 20 Cerebrovascular side effects.
3.21
3.21. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 21 Hypertension.
3.22
3.22. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 22 Hyperglycemia.
3.23
3.23. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 23 Rash.
3.24
3.24. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 24 Respiratory side effects.
3.25
3.25. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 25 Dry mouth.
3.26
3.26. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 26 Fatigue.
3.27
3.27. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 27 Dizziness.
3.28
3.28. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 28 Abnormal labs other than Cr. and LFT.
3.29
3.29. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 29 Withdrawal due to side effects.
3.30
3.30. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 30 Abdominal pain or dyspepsia.
3.31
3.31. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 31 Constipation or diarrhea.
3.32
3.32. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 32 Nausea or vomiting.
3.33
3.33. Analysis
Comparison 3 NSAIDs vs. placebo, Outcome 33 Death.
4.1
4.1. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 1 Nausea or vomiting.
4.2
4.2. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 2 Gastrointestinal side effects.
4.3
4.3. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 3 Elevated creatinine.
4.4
4.4. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 4 Elevated liver function test.
4.5
4.5. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 5 Hypertension.
4.6
4.6. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 6 Headache.
4.7
4.7. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 7 Psychiatric side effects.
4.8
4.8. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 8 Heart disease.
4.9
4.9. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 9 Cerebrovascular side effects.
4.10
4.10. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 10 Hyperglycemia.
4.11
4.11. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 11 Dry mouth.
4.12
4.12. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 12 Fatigue.
4.13
4.13. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 13 Dizziness.
4.14
4.14. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 14 Abnormal labs other than Cr. and LFT.
4.15
4.15. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 15 Death.
4.16
4.16. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 16 Withdrawal due to side effects.
4.17
4.17. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 17 Abdominal pain or dyspepsia.
4.18
4.18. Analysis
Comparison 4 Traditional NSAIDs vs. placebo, Outcome 18 Constipation or diarrhea.
5.1
5.1. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 1 Gastrointestinal side effects.
5.2
5.2. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 2 Hypertension.
5.3
5.3. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 3 Heart disease.
5.4
5.4. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 4 Rash.
5.5
5.5. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 5 Headache.
5.6
5.6. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 6 Psychiatric side effects.
5.7
5.7. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 7 Bleeding.
5.8
5.8. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 8 Cerebrovascular side effects.
5.9
5.9. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 9 Respiratory side effects.
5.10
5.10. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 10 Dry mouth.
5.11
5.11. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 11 Fatigue.
5.12
5.12. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 12 Dizziness.
5.13
5.13. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 13 Abnormal labs other than Cr. and LFT.
5.14
5.14. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 14 Death.
5.15
5.15. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 15 Withdrawal due to side effects.
5.16
5.16. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 16 Abdominal pain or dyspepsia.
5.17
5.17. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 17 Constipation or diarrhea.
5.18
5.18. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 18 Nausea or vomiting.
5.19
5.19. Analysis
Comparison 5 Selective COX‐2 inhibitor vs. placebo, Outcome 19 Abnormal liver function test.
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Leuchtenberger 2006 {published data only}
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Nawata 2002 {published data only}
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Nourhashemi 1998 {published data only}
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