Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients

Judge, Andrew; Garriga, César; Arden, N K; Lovestone, Simon; Prieto-Alhambra, D; Cooper, Cyrus; Edwards, Christopher J

doi:10.1016/j.trci.2017.10.002

Cited by 64 publications

(58 citation statements)

References 40 publications

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“…These results add to the evidence that inflammation may exacerbate cognitive impairment, and that anti-inflammatory agents may be disease modifying. The result of the present study is consistent with previous studies [19]. In addition, the effect was dose dependent, which may be explained by higher cumulative dosages suppressing inflammation more intensely.…”

Section: Discussionsupporting

confidence: 93%

“…Chou et al [20] reported that DMARD use was associated with an increased risk of dementia in patients with RA. However, another study conducted by Judge et al [19] suggested that DMARD users were at reduced risk of dementia compared with non-DMARD users. Whether an association exists between different ages or genders is still inconclusive.…”

Section: Introductionmentioning

confidence: 98%

“…In a systemic review, DMARD use was associated with a reduced risk of cardiovascular disease events in patients with RA where inflammatory insult was caused [18]. However, there have only been a few studies regarding the association between DMARD use and dementia risk in patients with RA [19,20] and the results of these studies were conflicting. Chou et al [20] reported that DMARD use was associated with an increased risk of dementia in patients with RA.…”

Section: Introductionmentioning

confidence: 99%

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Can Disease-Modifying Anti-Rheumatic Drugs Reduce the Risk of Developing Dementia in Patients with Rheumatoid Arthritis?

2019

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Disease-modifying anti-rheumatic drugs (DMARDs) can reduce inflammation and slow progression of rheumatoid arthritis (RA). It remains unknown what impact DMARDs may have on dementia, where inflammation also plays a critical role in pathogenesis. Patients without a prior history of dementia who were newly diagnosed with RA between 2000 and 2005 were identified from Taiwan's National Health Insurance Research Database. The participants were stratified by age and gender. The outcome of interest was all-cause dementia, and Cox regression models were used to estimate the hazard ratio (HR) of dementia. The cumulative DMARD dosage was stratified by quartiles of defined daily doses. A total of 20,707 patients were diagnosed with RA, and 62,121 non-RA individuals aged 20 years or older were included. Cox proportional hazard regression analysis revealed that the RA cohort was 37% less likely to develop dementia compared with the non-RA cohort [adjusted HR 0.63, 95% confidence interval (CI) 0.55-0.72]. Further decreased risk was noted in DMARD users (adjusted HR 0.48, 95% CI 0.39-0.58) with dose-dependent effect. Subgroup analysis identified DMARD use as having a protective effect against developing dementia in female and younger patients. Also, in male and older patients, DMARD use further reduced the risk. These observations suggest that DMARDs may reduce the risk of developing dementia, and its effect is further increased at high cumulative dosages. These findings warrant further examination in randomized control trials.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Can Disease-Modifying Anti-Rheumatic Drugs Reduce the Risk of Developing Dementia in Patients with Rheumatoid Arthritis?

2019

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“…The relationship between Alzheimer's disease and rheumatoid arthritis has been studied before using genetic-based methods such as Mendelian randomization [38], hence it is not examined here. We examined the use of methotrexate (anti-inflammatory drug for rheumatoid arthritis) due to observational studies [39,40] suggesting anti-inflammatory medicines for rheumatoid arthritis reduces risk of Alzheimer's disease [39]. At the time of the analysis, plasma glucose was not available and was not investigated.…”

Section: Risk Factors Implicated In Alzheimer's Disease In Previous Rmentioning

confidence: 99%

The causes and consequences of Alzheimer’s disease: phenome-wide evidence from Mendelian randomization

Korologou-Linden

Howe

Millard

et al. 2019

Preprint

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Importance Alzheimer's disease is the leading cause of disability and healthy life years lost. However, to date, there are no proven causal and modifiable risk factors, or effective interventions. Objective We aimed to identify: a) factors modified by prodromal Alzheimer's disease pathophysiology and b) causal risk factors for Alzheimer's disease. We identified factors modified by Alzheimer's disease using a phenome-wide association study (PheWAS) on the Alzheimer's disease polygenic risk score (PRS) (p≤5×10-8), stratified by age tertiles. We used two-sample bidirectional Mendelian randomization (MR) to estimate the causal effects of identified risk factors and correlates on liability for Alzheimer's disease. Design, setting, and participants 334,968 participants of the UK Biobank aged 39 to 72 years old (111,656 in each tertile) met our eligibility criteria. Exposures Standardized weighted PRS for Alzheimer's disease at p≤5×10-8. Main outcomes and measures All available phenotypes in UK Biobank, including data on health and lifestyle, as well as samples from urine, blood and saliva, at the time of analysis. Results Genetic liability for Alzheimer's disease was associated with red blood cell indices and cognitive measures at all ages. In the middle and older age tertiles, ages 53 and above, higher genetic liability for Alzheimer′s disease was adversely associated with medical history (e.g. atherosclerosis, use of cholesterol-lowering medications), physical measures (e.g. body fat measures), blood cell indices (e.g. red blood cell distribution width), cognition (e.g. fluid intelligence score) and lifestyle (e.g. self-reported moderate activity). In follow-up analyses using MR, there was only evidence that education, fluid intelligence score, hip circumference, forced vital capacity, and self-reported moderate physical activity were likely to be causal risk factors for Alzheimer's disease. Conclusion and relevance Genetic liability for Alzheimer's disease is associated with over 160 phenotypes, some as early as age 39 years. However, findings from MR analyses imply that most of these associations are likely to be a consequence of prodromal disease or selection, rather than a cause of the disease.

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“…Patients with the autoimmune disease Sjögren's syndrome (SS) are twice as likely to develop AD [46]. In RA, it has been shown that anti-TNF-α therapy has a protective effect on dementia [47]. In the case of depression, Aβ accumulation in AD mouse models induces depressive-like behavior, which is dependent on inflammation [23].…”

Section: Role Of Peripheral Inflammation In Admentioning

confidence: 99%

The Role of Inflammation in Amyloid Diseases

Foguel¹

2019

Amyloid Diseases

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Amyloid diseases are characterized by the abnormal accumulation of proteinaceous aggregates (amyloid fibrils or plaques) in tissues and organs. This class of diseases is also characterized by the presence of inflammation. Amyloid fibrils arise from the partial denaturing and unfolding of native proteins. The accumulation of amyloid fibrils causes tissue damage and elicits local and nonlocal immune cell infiltration into tissue and proinflammatory cytokine production. Moreover, these conditions fuel a vicious cycle that can increase amyloid production and create an environment of chronic inflammation. A chronically inflamed tissue rapidly deteriorates and loses its function. In this chapter, we will discuss important data gathered over the years describing the role of inflammation in amyloid diseases. We will describe how inflammation begins and how it affects disease progression for major amyloid diseases, such as Alzheimer's disease (AD) and hereditary TTR amyloidosis (hATTR). Lastly, we will discuss the recent advancements in treatments for amyloid diseases and how they address inflammation in affected patients.

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Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients

Cited by 64 publications

References 40 publications

Can Disease-Modifying Anti-Rheumatic Drugs Reduce the Risk of Developing Dementia in Patients with Rheumatoid Arthritis?

Can Disease-Modifying Anti-Rheumatic Drugs Reduce the Risk of Developing Dementia in Patients with Rheumatoid Arthritis?

The causes and consequences of Alzheimer’s disease: phenome-wide evidence from Mendelian randomization

The Role of Inflammation in Amyloid Diseases

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