Can leukotriene receptors inhibitors preserve cognitive functions in asthma patients?

Leukotriene receptors inhibitors and cognition

  • Dejan Aleksic University of Kragujevac, Serbia, Faculty of Medical Sciences, Department of Neurology, Uniiversity Clinical Center Kragujevac, Clinic of Neurology
  • Snezana Lazarevic University of Kragujevac, Faculty of Medical Sciences, Department of neurology, University Clinical Center Kragujevac, Clinic of Neurology, Kragujevac, Serbia
  • Romana Susa Pulmonology Clinic, University Clinical Centre Kragujevac, Kragujevac, Serbia
  • Zorica Lazic Faculty of Medical Sciences, University of Kragujevac, and Clinic for Pulmonology, University Clinical Centre, Kragujevac, Serbia
  • Ivan Cekerevac University of Kragujevac, Serbia, Faculty of Medical Sciences, Department of Internal medicine, Univesity clinical center Kragujevac, Clinic for Pulmology, Kragujevac, Serbia
  • Gordana Toncev University of Kragujevac, Serbia, Faculty of Medical Sciences, Department of Neurology, University clinical center Kragujevac, Clinic of Neurology, Kragujevac, Serbia
DOI: https://doi.org/10.5937/mckg59-53102
Keywords: cognitive functions, MoCA, naming, delayed recall, montelukast

Abstract


Background: Recent research suggests that neuroinflammation may play a crucial role in age-related cognitive dysfunction. Studies have investigated the impact of leukotriene receptor inhibitors (LTR) antagonist montelukast, a medication commonly used to treat allergies and asthma, on the risk of developing dementia. The aim of this study was to compare cognitive functions in asthmatic patients who used and who don’t use montelukast and healthy controls.

Method: In this study 50 asthmatic patients (age 67.34±6.44) (20 montelukast users and 30 montelukast nonusers) were matched with 50 healthy controls (age 68.08±5.95). Each participant was assessed with the Mini Mental State Examination (MMSE) and the Montreal Cognitive Test (MoCA). Memory coefficients (verbal, visual, general, delayed memory, and attention and concentration) were measured by Wechsler Memory Scale-Revised (WMS-R).

Results: Orientation as MoCA subdomain was worse in patients with asthma compared to the control group (p=0.048). Asthmatic patients treated with montelukast had a significantly higher MoCA score (p=0.033) (dominantly due to delayed recall) (p=0.044) than patients without montelukast treatment. People with asthma on montelukast therapy showed statistically significantly better results on the MoCA test (p=0.037) compared to the control group (dominantly due to attention (p=0.032) and delayed recall (p=0.021)). 

Conclusion: Montelukast group compared to montelukast nonusers had better results on MoCA (dominantly due to delayed recall). Studies with a larger number of participants are needed to confirm the effect of montelukast on the cognitive status of the elderly.

References

1. Brito DVC, Esteves F, Rajado AT, Silva N; ALFA score Consortium; Araújo I, Bragança J, Castelo-Branco P, Nóbrega C. Assessing cognitive decline in the aging brain: lessons from rodent and human studies. NPJ Aging. 2023;9(1):23.
2. Krause DL, Müller N. Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease. Int J Alzheimers Dis. 2010;2010:732806.
3. Huber C, Marschallinger J, Tempfer H, Furtner T, Couillard-Despres S, Bauer HC, Rivera FJ, Aigner L. Inhibition of leukotriene receptors boosts neural progenitor proliferation. Cell Physiol Biochem. 2011;28(5):793-804.
4. Marschallinger J, Schäffner I, Klein B, Gelfert R, Rivera FJ, Illes S, Grassner L, Janssen M, Rotheneichner P, Schmuckermair C, Coras R, Boccazzi M, Chishty M, Lagler FB, Renic M, Bauer HC, Singewald N, Blümcke I, Bogdahn U, Couillard-Despres S, Lie DC, Abbracchio MP, Aigner L. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug. Nat Commun. 2015;6:8466.
5. Michael J, Zirknitzer J, Unger MS, Poupardin R, Rieß T, Paiement N, Zerbe H, Hutter-Paier B, Reitsamer H, Aigner L. The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice. Int J Mol Sci. 2021;22(5):2782.
6. Marschallinger J, Altendorfer B, Rockenstein E, Holztrattner M, Garnweidner-Raith J, Pillichshammer N, Leister I, Hutter-Paier B, Strempfl K, Unger MS, Chishty M, Felder T, Johnson M, Attems J, Masliah E, Aigner L. The Leukotriene Receptor Antagonist Montelukast Reduces Alpha-Synuclein Load and Restores Memory in an Animal Model of Dementia with Lewy Bodies. Neurotherapeutics. 2020;17(3):1061-1074.
7. Mrowetz H, Kotob MH, Forster J, Aydin I, Unger MS, Lubec J, Hussein AM, Malikovic J, Feyissa DD, Korz V, Höger H, Lubec G, Aigner L. Leukotriene signaling as molecular correlate for cognitive heterogeneity in aging: an exploratory study. Front Aging Neurosci. 2023;15:1140708.
8. Rahman SO, Singh RK, Hussain S, Akhtar M, Najmi AK. A novel therapeutic potential of cysteinyl leukotrienes and their receptors modulation in the neurological complications associated with Alzheimer's disease. Eur J Pharmacol. 2019;842:208-220.
9. Grinde B, Engdahl B. Prescription database analyses indicates that the asthma medicine montelukast might protect against dementia: a hypothesis to be verified. Immun Ageing. 2017;14:20.
10. Yerraguravagari B, Penchikala NP, Kolusu AS, Sandeep Ganesh G, Konduri P, Nemmani KVS, Samudrala PK. Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF. CNS Neurol Disord Drug Targets. 2023 Sep 27. doi: 10.2174/0118715273258337230925040049. Epub ahead of print. PMID: 37779395.
11. Rozin SI. Case Series Using Montelukast in Patients with Memory Loss and Dementia. Open Neurol J. 2017; 11:7-10.
12. Lo CWH, Pathadka S, Qin SX, Fung LWY, Yan VKC, Yiu HHE, Bloom CI, Wong ICK, Chan EWY. Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review. Eur Respir Rev. 2023 Sep;32(169):230079.
13. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-98.
14. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695-9.
15. Dejan Lalović, Aleksandra Stanković. Neka svojstva kratkoročnog verbalnog pamćenja depresivnih pacijenata. Psihološka istraživanja. 2012; Vol. XV (1) 23-35.
16. Maesawa S, Bagarinao E, Fujii M, Futamura M, Motomura K, Watanabe H, Mori D, Sobue G, Wakabayashi T. Evaluation of resting state networks in patients with gliomas: connectivity changes in the unaffected side and its relation to cognitive function. PLoS One. 2015;10(2):e0118072.
17. Pietrzak D, Pietrzak A, Krasowska D, Makara-Studzińska M, Madej A, Baranowska M, Borzęcki A. Depressiveness, measured with Beck Depression Inventory, in patients with psoriasis. J Affect Disord. 2017;209:229-234.
18. Nair AK, Van Hulle CA, Bendlin BB, Zetterberg H, Blennow K, Wild N, Kollmorgen G, Suridjan I, Busse WW, Rosenkranz MA. Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline. Alzheimers Dement (N Y). 2022;8(1):e12315.
19. Mendelsohn AR, Larrick JW. Pharmaceutical Rejuvenation of Age-Associated Decline in Spatial Memory. Rejuvenation Res. 2016; 19(6):521-524.
20. Grinde B, Schirmer H, Eggen AE, Aigner L, Engdahl B. A possible effect of montelukast on neurological aging examined by the use of register data. Int J Clin Pharm. 2021;43(3):541-548.
21. Ishikura Y, Maeda-Minami A, Hosokawa M, Onoda A, Kawano Y, Ihara T, Sugamata M, Takeda K, Mano Y. Leukotriene Receptor Antagonist Use and Dementia Risk in Patients With Asthma: A Retrospective Cohort Study. In Vivo. 2021;35(6):3297-3303.
22. Xiong LY, Ouk M, Wu CY, Rabin JS, Lanctôt KL, Herrmann N, Black SE, Edwards JD, Swardfager W. Leukotriene receptor antagonist use and cognitive decline in normal cognition, mild cognitive impairment, and Alzheimer's dementia. Alzheimers Res Ther. 2021; 13(1):147.
23. Michael J, Marschallinger J, Aigner L. The leukotriene signaling pathway: a druggable target in Alzheimer's disease. Drug Discov Today. 2019;24(2):505-516.
Published
2025/09/04
Issue
Vol. 59 No. 1 (2025): MEDICINSKI ČASOPIS
Section
Original Scientific Paper