Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and Meta-analysis
Corresponding Author
Nicola Veronese MD
Institute for Clinical Research and Education in Medicine, Padova, Italy
Aging Section, Institute of Neurosciences, Italian Research Council, Padova, Italy
Joint first authorsAddress correspondence to: Nicola Veronese, Aging Section, Institute of Neurosciences, Italian Research Council, Padova, Italy, Via Giustiniani, 2—35128 Padova, Italy. E-mail: [email protected]Search for more papers by this authorBrendon Stubbs PhD
Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK
South London and Maudsley National Health Service Foundation Trust, London, UK
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Joint first authorsSearch for more papers by this authorStefania Maggi MD
Aging Section, Institute of Neurosciences, Italian Research Council, Padova, Italy
Search for more papers by this authorTrevor Thompson PhD
Faculty of Education and Health, University of Greenwich, London, UK
Search for more papers by this authorPatricia Schofield PhD
Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK
Search for more papers by this authorChristoph Muller MD
South London and Maudsley National Health Service Foundation Trust, London, UK
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Search for more papers by this authorPing-Tao Tseng MD
Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan
Search for more papers by this authorPao-Yen Lin MD
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorAndré F. Carvalho MD
Translational Psychiatry Research Group, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil
Search for more papers by this authorMarco Solmi MD
Institute for Clinical Research and Education in Medicine, Padova, Italy
Department of Neuroscience, University of Padova, Padova, Italy
Search for more papers by this authorCorresponding Author
Nicola Veronese MD
Institute for Clinical Research and Education in Medicine, Padova, Italy
Aging Section, Institute of Neurosciences, Italian Research Council, Padova, Italy
Joint first authorsAddress correspondence to: Nicola Veronese, Aging Section, Institute of Neurosciences, Italian Research Council, Padova, Italy, Via Giustiniani, 2—35128 Padova, Italy. E-mail: [email protected]Search for more papers by this authorBrendon Stubbs PhD
Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK
South London and Maudsley National Health Service Foundation Trust, London, UK
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Joint first authorsSearch for more papers by this authorStefania Maggi MD
Aging Section, Institute of Neurosciences, Italian Research Council, Padova, Italy
Search for more papers by this authorTrevor Thompson PhD
Faculty of Education and Health, University of Greenwich, London, UK
Search for more papers by this authorPatricia Schofield PhD
Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK
Search for more papers by this authorChristoph Muller MD
South London and Maudsley National Health Service Foundation Trust, London, UK
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Search for more papers by this authorPing-Tao Tseng MD
Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan
Search for more papers by this authorPao-Yen Lin MD
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorAndré F. Carvalho MD
Translational Psychiatry Research Group, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil
Search for more papers by this authorMarco Solmi MD
Institute for Clinical Research and Education in Medicine, Padova, Italy
Department of Neuroscience, University of Padova, Padova, Italy
Search for more papers by this authorAbstract
Objectives
To investigate whether low-dose aspirin (<300 mg/d) can influence the onset of cognitive impairment or dementia in observational studies and improve cognitive test scores in randomized controlled trials (RCTs) in participants without dementia.
Design
Systematic review and meta-analysis.
Setting
Observational and interventional studies.
Participants
Individuals with no dementia or cognitive impairment initially.
Measurements
Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for the maximum number of covariates from each study, were used to summarize data on the incidence of dementia and cognitive impairment in observational studies. Standardized mean differences (SMDs) were used for cognitive test scores in RCTs.
Results
Of 2,341 potentially eligible articles, eight studies were included and provided data for 36,196 participants without dementia or cognitive impairment at baseline (mean age 66, 63% female). After adjusting for a median of three potential confounders over a median follow-up period of 6 years, chronic use of low-dose aspirin was not associated with onset of dementia or cognitive impairment (5 studies, N = 26,159; OR = 0.82, 95% CI = 0.55–1.22, P = .33, I2 = 67%). In three RCTs (N = 10,037; median follow-up 5 years), the use of low-dose aspirin was not associated with significantly better global cognition (SMD=0.005, 95% CI=–0.04–0.05, P = .84, I2 = 0%) in individuals without dementia. Adherence was lower in participants taking aspirin than in controls, and the incidence of adverse events was higher.
Conclusion
This review found no evidence that low-dose aspirin buffers against cognitive decline or dementia or improves cognitive test scores in RCTs.
Supporting Information
| Filename | Description |
|---|---|
| jgs14883-sup-0001-SupInfo.docxWord document, 47.1 KB |
Figure S1. PRISMA flow-chart. Table S1. Descriptive characteristics of the longitudinal studies included. Table S2. Descriptive characteristics of the randomized controlled trials included. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. Am J Cardiol 2011; 107: 1796–1801.
- 2Berger JS, Lala A, Krantz MJ et al. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: A meta-analysis of randomized trials. Am Heart J 2011; 162: 115.e2–124.e2.
- 3Soysal P, Stubbs B, Lucato P et al. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Res Rev 2016; 31: 1–8.
- 4Wu Y, Zhai H, Wang Y et al. Aspirin-triggered lipoxin A 4 attenuates lipopolysaccharide- induced intracellular ROS in BV2 microglia cells by inhibiting the function of NADPH oxidase. Neurochem Res 2012; 37: 1690–1696.
- 5Wang Y-P, Wu Y, Li L-Y et al. Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. J Neuroinflammation 2011; 8: 95.
- 6Tatemichi TK, Paik M, Bagiella E et al. Risk of dementia after stroke in a hospitalized cohort: Results of a longitudinal study. Neurology 1994; 44: 1885–1891.
- 7Newman AB, Fitzpatrick AL, Lopez O et al. Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J Am Geriatr Soc 2005; 53: 1101–1107.
- 8Harrison SL, Ding J, Tang EYH et al. Cardiovascular disease risk models and longitudinal changes in cognition: A systematic review. PLoS ONE 2014; 9: e114431.
- 9Trevisan C, Veronese N, Bolzetta F et al. Low hemoglobin levels and the onset of cognitive impairment in older people: The PRO.V.A. Study. Rejuvenation Res 2016; 19: 447–455.
- 10Li L, Hölscher C. Common pathological processes in Alzheimer disease and type 2 diabetes: A review. Brain Res Rev 2007; 56: 384–402.
- 11Katon W, Pedersen HS, Ribe AR et al. Effect of depression and diabetes mellitus on the risk for dementia: A national population-based cohort study. JAMA Psychiatry 2015; 98195: 1–8.
- 12Williams PS, Rands G, Orrel M et al. Aspirin for vascular dementia. Cochrane Database Syst Rev 2000; 4: CD001296.
- 13Wang J, Tan L, Wang H-F et al. Anti-inflammatory drugs and risk of Alzheimer's disease: An updated systematic review and meta-analysis. J Alzheimers Dis 2015; 44: 385–396.
- 14Liberati A, Altman DG, Tetzlaff J et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med 2009; 6: e1000100.
- 15Stroup DF, Berlin J, Morton SC et al. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008–2012.
- 16Lloyd J, Bochner F. Aspirin: How low is low dose? Aust Prescr 1996; 19: 79–81.
10.18773/austprescr.1996.070 Google Scholar
- 17Folstein M, Robins L, Helzer J. The Mini-Mental State Examination. Arch Gen Psychiatry 1983; 40: 812.
- 18Wells G, Shea B, O'Connell D et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses [on-line]. Available at http// www.ohri.ca/programs/clinical_epidemiology/oxford.asp Accessed on 1st October 2016.
- 19Jadad AR, Moore RA, Carroll D et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17: 1–12.
- 20DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.
- 21Higgins JPT, Thompson SG, Deeks JJ et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.
- 22Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088–1101.
- 23Egger M, Davey Smith G, Schneider M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.
- 24Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56: 455–463.
- 25Kern S, Skoog I, Östling S et al. Does low-dose acetylsalicylic acid prevent cognitive decline in women with high cardiovascular risk? A 5-year follow-up of a non-demented population-based cohort of Swedish elderly women BMJ Open 2012; 3;2(5).
- 26Kelley BJ, McClure LA, Unverzagt FW, et al. Regular aspirin use does not reduce risk of cognitive decline. J Am Geriatr Soc. 2015; 63: 390–392.
- 27Nilsson SE, Johansson ÆB, Takkinen ÆS. Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged > or = 80 years. Eur J Clin Pharmacol 2003; 59: 313–319.
- 28Williams-Gray C, Mason S, Foltinye T et al. Williams Gray.pdf 2014; 24: S553.
- 29Jonker C, Comijs HC, Smit JH. Does aspirin or other NSAIDs reduce the risk of cognitive decline in elderly persons? Results from a population-based study. Neurobiol Aging 2003; 24: 583–588.
- 30Price JF, Stewart MC, Deary IJ et al. Low dose aspirin and cognitive function in middle aged to elderly adults: Randomised controlled trial. BMJ 2008; 337: a1198.
- 31 AD2000 Collaborative Group. Aspirin in Alzheimer's disease (AD2000): A randomised open-label trial. Lancet Neurol 2008; 7: 41–49.
- 32Kang JH, Cook N, Manson J et al. Low dose aspirin and cognitive function in the women's health study cognitive cohort. BMJ 2007; 334: 987.
- 33Reiman EM, Quiroz YT, Fleisher AS et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: A case-control study. Lancet Neurol 2012; 11: 1048–1056.
- 34Szekely CA, Breitner JCS, Fitzpatrick AL et al. NSAID use and dementia risk in the Cardiovascular Health Study: Role of APOE and NSAID type. Neurology 2008; 70: 17–24.
- 35Naugle RI, Kawczak K. Limitations of the Mini-Mental State Examination. Cleve Clin J Med 1989; 56: 277–281.
- 36Miguel-Alvarez M, Santos-Lozano A, Sanchis-Gomar F et al. Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect. Drugs Aging 2015; 32: 139–147.
- 37 ASPREE Investigator Group. Study design of ASPirin in Reducing Events in the Elderly (ASPREE): A randomized, controlled trial. Contemp Clin Trials 2013; 36: 555–564.
- 38Ahlskog JE, Geda YE, Graff-Radford NR et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc 2011; 86: 876–884.
- 39Lautenschlager NT, Cox KL, Flicker L et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: A randomized trial. JAMA 2008; 300: 1027–1037.
- 40Ngandu T, Lehtisalo J, Solomon A et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial. Lancet 2015; 385: 2255–2636.
- 41Carabotti M, Scirocco A, Maselli MA et al. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015; 28: 203–209.
- 42Hollander D. Intestinal permeability, leaky gut, and intestinal disorders. Curr Gastroenterol Rep 1999; 1: 410–416.
- 43Haukoos JS, Lewis RJ. The propensity score. JAMA 2015; 314: 1637–1638.
- 44 JPT Higgins, S Green (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011.
