Midlife Rheumatoid Arthritis Increases the Risk of Cognitive Impairment Two Decades Later: A Population-Based Study

Wallin, Karin; Solomon, Alina; Kåreholt, Ingemar; Tuomilehto, Jaakko; Soininen, Hilkka; Kivipelto, Miia

doi:10.3233/jad-2012-111736

Cited by 101 publications

(94 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These processes might participate in a positive feedback loop of Aβ deposition, neurofibrillary tangle formation, and damage to synapses and neurons. Several studies have shown that other conditions involving chronic systemic inflammation, such as rheumatoid arthritis and periodontitis, are associated with an increased risk of AD 132,133 . These conditions are also associated with elevated levels of C-reactive protein and proinflammatory cytokines, such as tumour necrosis factor, IL-6 and IL-1β.…”

Section: Systemic Inflammationmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

View full text Add to dashboard Cite

The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

show abstract

Section: Systemic Inflammationmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

View full text Add to dashboard Cite

show abstract

“…2 Such systemic inflammation is causally associ ated with the development of many chronic diseases, including type 2 diabetes mellitus, atherosclerosis, cardiovascular events, dementia and anaemia. 3,18 Notably, these comorbidities are also common in patients with inflammatory rheumatic diseases (as reviewed elsewhere [3][4][5]19 ).…”

Section: The 'Vicious Cycle'mentioning

confidence: 99%

Exercise as an anti-inflammatory therapy for rheumatic diseases—myokine regulation

2014

View full text Add to dashboard Cite

Persistent systemic inflammation, a typical feature of inflammatory rheumatic diseases, is associated with a high cardiovascular risk and predisposes to metabolic disorders and muscle wasting. These disorders can lead to disability and decreased physical activity, exacerbating inflammation and the development of a network of chronic diseases, thus establishing a 'vicious cycle' of chronic inflammation. During the past two decades, advances in research have shed light on the role of exercise as a therapy for rheumatic diseases. One of the most important of these advances is the discovery that skeletal muscle communicates with other organs by secreting proteins called myokines. Some myokines are thought to induce anti-inflammatory responses with each bout of exercise and mediate long-term exercise-induced improvements in cardiovascular risk factors, having an indirect anti-inflammatory effect. Therefore, contrary to fears that physical activity might aggravate inflammatory pathways, exercise is now believed to be a potential treatment for patients with rheumatic diseases. In this Review, we discuss how exercise disrupts the vicious cycle of chronic inflammation directly, after each bout of exercise, and indirectly, by improving comorbidities and cardiovascular risk factors. We also discuss the mechanisms by which some myokines have anti-inflammatory functions in inflammatory rheumatic diseases.

show abstract

“…Therefore, some of the prior literature investigated the potential association between RA and AD because these two diseases may share similar inflammatory mechanisms. Nevertheless, to date, findings of the previous literature are still controversial, and some methodological limitations were observed in those studies [19–22]. According to studies in the 1990s, patients with RA have a reduced risk of AD; however, recent research showed that RA may increase the risk of cognitive impairment [19–22].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, to date, findings of the previous literature are still controversial, and some methodological limitations were observed in those studies [19–22]. According to studies in the 1990s, patients with RA have a reduced risk of AD; however, recent research showed that RA may increase the risk of cognitive impairment [19–22]. Consequently, in order to clarify this important issue, the aim of this study was to investigate the relationship between prior RA and AD using a large population-based dataset in Taiwan.…”

Section: Introductionmentioning

confidence: 99%

Rheumatoid Arthritis Was Negatively Associated with Alzheimer’s Disease: A Population-Based Case-Control Study

et al. 2016

View full text Add to dashboard Cite

Some of the prior literature investigated the potential association between rheumatoid arthritis (RA) and Alzheimer's disease (AD) because these two diseases may share similar inflammatory mechanisms. Nevertheless, to date, findings of the previous literature are still controversial, and some methodological limitations were observed in those studies. The aim of this case-control study was to investigate the relationship between prior RA and AD using a large population-based dataset. This study used the Taiwan Longitudinal Health Insurance Database 2005. We included 2271 patients with AD who had received prescriptions for acetylcholinesterase inhibitors (AChEIs) as cases and 6813 patients without AD as controls in this study. In addition, we performed a conditional logistic regression to examine the odds ratio (OR) and 95% confidence interval (CI) for prior RA between cases and controls. The study found that 330 (3.63%) of the total sampled patients had an RA diagnosis before the index date. Additionally, prior RA was found in 60 (2.64%) cases and in 270 (3.96%) controls. The conditional logistic regression analysis showed that the crude OR of prior RA for cases was 0.66 (95% confidence interval (CI): 0.49~0.87) compared to controls. After adjusting for patients’ geographic location, urbanization level, and comorbidities, the adjusted OR of prior RA for patients with AD was 0.73 (95% CI: 0.55~0.98) compared to those without AD. We concluded that there was an inverse association between prior RA and AD even after adjusting for potential confounders.

show abstract

Midlife Rheumatoid Arthritis Increases the Risk of Cognitive Impairment Two Decades Later: A Population-Based Study

Cited by 101 publications

References 0 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Exercise as an anti-inflammatory therapy for rheumatic diseases—myokine regulation

Rheumatoid Arthritis Was Negatively Associated with Alzheimer’s Disease: A Population-Based Case-Control Study

Contact Info

Product

Resources

About