Leukotriene Receptor Antagonist Use and Dementia Risk in Patients With Asthma: A Retrospective Cohort Study

Ishikura, Yumi; Maeda-Minami, Ayako; Hosokawa, Maiko; Onoda, Atsuto; Kawano, Yoshinobu; Ihara, Tomomi; Sugamata, Masao; Takeda, Ken; Mano, Yasunari

doi:10.21873/invivo.12625

Cited by 6 publications

(10 citation statements)

References 27 publications

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“…30 In a small cohort of asthma patients, leukotriene receptor antagonists decreased risk of dementia. 31 Third, allergy may induce vascular pathology and cerebrovascular dysfunction. In many previous studies, allergic diseases were associated with hypertension, diabetes, atherosclerosis, and cardiovascular and cerebrovascular diseases-established risk factors for dementia.…”

Section: Discussionmentioning

confidence: 99%

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Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease

Joh

Kwon

Son

et al. 2022

Annals of Neurology

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Objective: To examine the associations between the allergic triad (asthma, allergic rhinitis, atopic dermatitis) and risk of dementia. Methods: Participants comprised 6,785,948 adults aged ≥40 years who participated in a national health examination in 2009 without any history of dementia before baseline. From 2009 to 2017, we prospectively investigated the associations between physician-diagnosed allergic diseases and risk of incident dementia (all-cause, Alzheimer's disease [AD], vascular dementia [VaD]) ascertained using national health insurance claims data. Results: During 8.1 years of follow-up, 260,705 dementia cases (195,739 AD,32,789 VaD) were identified. Allergic diseases were positively associated with dementia risk. Compared with individuals without allergic diseases, multivariable hazard ratios (HRs) of all-cause dementia were 1.20 (95% confidence interval [CI] 1.19-1.22) in those with asthma, 1.10 (95% CI 1.09-1.12) with allergic rhinitis, 1.16 (95% CI 1.11-1.21) with atopic dermatitis, and 1.13 (95% CI 1.12-1.14) with any of these allergies. Similarly, individuals with any of the allergic triad had a higher risk of AD (HR 1.16, 95% CI 1.14-1.17) and VaD (HR 1.04; 95% CI 1.01-1.06) than those without any allergic disease. As the number of comorbid allergic diseases increased, the risk of dementia increased linearly (P trend ≤ 0.002). Compared with individuals without allergies, those with all three allergic diseases had substantially increased risk of all-cause dementia (

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Section: Discussionmentioning

confidence: 99%

“…In a phase II randomized placebo‐controlled trial, a mast cell inhibitor added to standard care delayed cognitive decline in mild‐to‐moderate AD 30 . In a small cohort of asthma patients, leukotriene receptor antagonists decreased risk of dementia 31 …”

Section: Discussionmentioning

confidence: 99%

Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease

Joh

Kwon

Son

et al. 2022

Annals of Neurology

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“…Stosowanie inhibitorów 5-LOX i FLAP hamuje akumulację Aβ w tkankach [114,118], natomiast antagoniści CysLT1R hamują aktywność TNF-α, IL-1β i szlaku NF-κB, co prowadzi do wyciszenia aktywności β-sekretazy oraz zmniejszenia stresu oksydacyjnego i poprawy funkcji poznawczych [73]. Działanie LTRA hamuje proces zapalny oraz zmniejsza przepuszczalność bariery krew-mózg, wobec czego mogą być one stosowane w przywracaniu prawidłowej funkcji i struktury układu nerwowego [117,119]. Blokowanie CysLT1R montelukastem lub pranlukastem może być skuteczne w leczeniu choroby Alzheimera przez zmniejszenie neurotoksyczności indukowanej Aβ, wyciszanie stanu zapalnego, hamowanie aktywności szlaków proapoptotycznych neuronów oraz poprawę funkcji poznawczych, przede wszystkim pamięci [116,119].…”

Section: Montelukastunclassified

“…Działanie LTRA hamuje proces zapalny oraz zmniejsza przepuszczalność bariery krew-mózg, wobec czego mogą być one stosowane w przywracaniu prawidłowej funkcji i struktury układu nerwowego [117,119]. Blokowanie CysLT1R montelukastem lub pranlukastem może być skuteczne w leczeniu choroby Alzheimera przez zmniejszenie neurotoksyczności indukowanej Aβ, wyciszanie stanu zapalnego, hamowanie aktywności szlaków proapoptotycznych neuronów oraz poprawę funkcji poznawczych, przede wszystkim pamięci [116,119]. Montelukast znajduje się II fazie badań klinicznych w leczeniu choroby Alzheimera, gdzie bada się jego potencjalne działanie nasilające wytwarzanie nowych neuronów, zmniejszające stan zapalny, poprawiające pamięć i funkcje poznawcze [73,120].…”

Section: Montelukastunclassified

Anti-leukotriene drugs in the therapy of inflammatory diseases

Karolina¹,

Pisklak²

2022

pps

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A key part of many chronic diseases is inflammation controlled by inflammatory mediators. Regulation of their function allows to mute the inflammatory response, which is a desired effect in the treatment of inflammatory diseases. The source of mediators is arachidonic acid, converted to pro-inflammatory mediators by cyclooxygenases (COX) or lipooxygenases (LOX). The 5-LOX pathway is full of target points for regulation of biosynthesis of cysteinyl leukotrienes (CysLT) – one of the major classes of inflammatory mediators. These compounds exert their activity through specific leukotriene receptors – first (CysLT1R) and second (CysLT2R). Drugs that inhibit CysLT synthesis as well as leukotriene receptors antagonists (LTRA) form group of drugs known as anti-leukotriene drugs. Currently, only a few representatives of this group are available in the pharmacies around the world: the 5-LOX inhibitor – zileuton – and three CysLT1R antagonists – montelukast, pranlukast, zafirlukast. LTRAs due to their wide range of anti-inflammatory effects, are a group of drugs with a high potential in the treatment of inflammatory diseases. The study of new applications of known LTRAs and the search for new members of the LTRA group are the main directions of development in this field of pharmacy. This work summarizes the benefits of using anti-leukotriene drugs in the treatment od chronic diseases and presents new directions of using LTRAs.

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“…Recent work using data from electronic health record databases worldwide has reported possible relationships between montelukast and neuropsychiatric events, such as sleeping disorders [ 7 ], depression [ 6 ], dementia [ 8 ] and attention deficit/hyperactivity disorder (ADHD) [ 9 ]. The largest observational study to date initiated by the FDA Sentinel Initiative revealed a reduced risk of outpatient depressive disorders [ 6 ], yet paediatric Canadian studies identified increased risk of neuropsychiatric events [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review

Lo,

Pathadka,

Qin

et al. 2023

Eur Respir Rev

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Background:The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown.Objective:To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma.Methods:A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded.Results:59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10threvision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children.Conclusion:Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.

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Leukotriene Receptor Antagonist Use and Dementia Risk in Patients With Asthma: A Retrospective Cohort Study

Cited by 6 publications

References 27 publications

Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease

Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease

Anti-leukotriene drugs in the therapy of inflammatory diseases

Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review

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