Beyond movement: exploring the combined impact of breathing exercises and the PEPSMAN protocol on cognitive and functional recovery in knee osteoarthritis
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20254466Keywords:
Breathing exercises, Cognitive decline, Grade II and grade III knee osteoarthritis, PEPSMAN protocol, Physical therapy, RehabilitationAbstract
Knee Osteoarthritis (KOA), a leading cause of disability globally, is linked to sedentary lifestyles, obesity, and chronic low-grade inflammation affecting joint and cognitive health. Physical exercise reduces oxidative stress and inflammation, benefiting brain health. The PEPSMAN protocol—combining patient education, exercise, and manual therapy—improves balance, pain, physical function, and reduces disability in KOA. Although limited, early evidence suggests combining PEPSMAN with breathing exercises offers additional benefits. This review synthesizes recent research on the interplay of inflammation, cognition, pain, and rehabilitation in Grade II–III KOA. A comprehensive search across databases like EMBASE, SCOPUS, DOAJ, PubMed, Google Scholar, and Web of Science identified peer-reviewed articles and clinical trials focusing on these factors in KOA.KOA progression associates with increased dementia and Alzheimer's disease risk; chronic pain significantly contributes to cognitive decline and functional impairment. Emerging studies reveal respiration influences cognitive performance. Combining breathing exercises with PEPSMAN enhances cognition and physical function in KOA by reducing inflammation, improving autonomic regulation, and promoting neuroplasticity, addressing joint symptoms and cognitive decline in a holistic approach. Chronic low-grade inflammation is central to KOA pathophysiology, driving joint damage and neurodegeneration linked to cognitive decline and Alzheimer’s disease risk. This highlights the need for integrative management targeting musculoskeletal and neurocognitive health.
Metrics
References
Kandasamy S, Vadivelu R, Shanmugam SK, Mahendran BS. Exploring the burden of knee osteoarthritis in rural South India:Community prevalence, risk factors, and functional assessment among adults aged 40 and above. Cureus. 2024;16(11):e73452. DOI: https://doi.org/10.7759/cureus.73452
Somaiya KJ, Samal S, Boob MA. Physiotherapeutic intervention techniques for knee osteoarthritis:A systematic review. Cureus. 2024;16(3):e56817. DOI: https://doi.org/10.7759/cureus.56817
Pal CP, Singh P, Chaturvedi S, Pruthi KK, Vij A. Epidemiology of knee osteoarthritis in India and related factors. Indian J Orthop. 2016;50(5):518-22. DOI: https://doi.org/10.4103/0019-5413.189608
Shumnalieva R, Kotov G, Monov S. Obesity-related knee osteoarthritis—current concepts. Life. 2023;13(8):1650. DOI: https://doi.org/10.3390/life13081650
Sattler L, Kan A, Hing W, Vertullo C. The addition of structured lifestyle modifications to a traditional exercise program for the management of patients with knee osteoarthritis:a systematic review and meta-analysis of randomised trials. Musculoskelet Sci Pract. 2023;68:102858. DOI: https://doi.org/10.1016/j.msksp.2023.102858
Li C, Hao C, Zhou K, Zhang P, Sun Q, Li Z. Inflammation-mediated regional brain alterations associated with mild cognitive impairment in knee osteoarthritis. Arthritis Res Ther. 2025;27(1):181. DOI: https://doi.org/10.1186/s13075-025-03646-0
Yao K, Wang S, Xu Z, Fan Z, Chen Z, Jia P, et al. Mechanisms of comorbidity between Alzheimer's disease and pain. Alzheimer's Dement. 2025;21(2):e14605. DOI: https://doi.org/10.1002/alz.14605
Wang L, Xie S, Bao T, Zhu S, Liang Q, Wang X, et al. Exercise and education for community-dwelling older participants with knee osteoarthritis:a video-linked programme protocol based on a randomised controlled trial. BMC Musculoskelet Disord. 2021;22(1):470. DOI: https://doi.org/10.1186/s12891-021-04331-4
Rizvi MR, Sharma A, Hasan S, Ahmad F, Asad MR, Iqbal A, et al. Exploring the impact of integrated polyvagal exercises and knee reinforcement in females with grade II knee osteoarthritis:a randomized controlled trial. Sci Rep. 2023;13(1):18964. DOI: https://doi.org/10.1038/s41598-023-45908-4
Burley CV, Casey AN, Jones MD, Wright KE, Parmenter BJ. Nonpharmacological approaches for pain and symptoms of depression in people with osteoarthritis:systematic review and meta-analyses. Sci Rep. 2023;13(1):15449. DOI: https://doi.org/10.1038/s41598-023-41709-x
Prasoon P, Nguyen KL, Fathi PA, Gupta S, Arnab S, Jones E, et al. Pathophysiological Mechanisms Linking Osteoarthritis and Neurodegenerative Disease Risk. Osteoarthritis Cartilage. 2025. DOI: https://doi.org/10.1016/j.joca.2025.10.009
Salazar-Méndez J, Cuyul-Vásquez I, Viscay-Sanhueza N, Morales-Verdugo J, Mendez-Rebolledo G, Ponce-Fuentes F, et al. Structural and functional brain changes in people with knee osteoarthritis:a scoping review. Peer J. 2023;11:e16003. DOI: https://doi.org/10.7717/peerj.16003
Li X, Tong Q, Gao J, Liu C, Alzheimer’s Disease Neuroimaging Initiative, Liu Y. Osteoarthritis was associated with a faster decline in hippocampal volumes in cognitively normal older people. Front Aging Neurosci. 2020;12:190. DOI: https://doi.org/10.3389/fnagi.2020.00190
Yadav AK, Shukla N. Comparison of Two Effective Advance Physiotherapy Intervention Protocol in Unilateral Knee Osteoarthritis. Int J Med Res Health. 2023;12(10):17-23.
Chieffi S, Messina G, Villano I, Messina A, Valenzano A, Moscatelli F, et al. Neuroprotective effects of physical activity:evidence from human and animal studies. Front neurol. 2017;8:188. DOI: https://doi.org/10.3389/fneur.2017.00188
Khan SA, Parasher P, Ansari MA, Parvez S, Fatima N, Alam I. Effect of an integrated physiotherapy protocol on knee osteoarthritis patients:a preliminary study. Healthcare. 2023; 11(4):564. DOI: https://doi.org/10.3390/healthcare11040564
Hooi LY, Chen PL, Tan KW, de Vries M, Wong HK. Effects of mindfulness breathing meditation on stress and cognitive functions:a heart rate variability and eye-tracking study. Sci Rep. 2025;15(1):37185. DOI: https://doi.org/10.1038/s41598-025-23727-z
Liu J, Tao J, Cai G, Chen J, Zhao L, Wang Y, Xu S, et al. The altered hippocampal functional connectivity and serum brain-derived neurotrophic factor level predict cognitive decline in patients with knee osteoarthritis. Cereb Cortex. 2023;33(20):10584-94. DOI: https://doi.org/10.1093/cercor/bhad305
Zhao B, Lian X, Zeng P, Wang Y, Cai G, Chen R, et al. Hippocampal Subfields Related to Cognitive Decline and Peripheral TIM-3 Levels in Elderly with Knee Osteoarthritis. J Pain Res. 2025;18:1697-709. DOI: https://doi.org/10.2147/JPR.S496944
Rabie MA, Madry H, Cucchiarini M, El-Sayed NS. The brain-joint axis:links between osteoarthritis and neurodegenerative disorders in aging. J Adv Res. 2025. DOI: https://doi.org/10.1016/j.jare.2025.10.023
Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. E Clin Med. 2020;29-30. DOI: https://doi.org/10.1016/j.eclinm.2020.100587
Acharya RN, Patel HM. Prevalence of the knee osteoarthritis risk factors among young adult population-an observational study. Int J Health Sci Res. 2023;13(10):158-63. DOI: https://doi.org/10.52403/ijhsr.20231022
Veronese N, Cooper C, Bruyère O, Al-Daghri NM, Branco J, Cavalier E, et al. Multimodal multidisciplinary management of patients with moderate to severe pain in knee osteoarthritis:a need to meet patient expectations. Drugs. 2022;82(13):1347-55. DOI: https://doi.org/10.1007/s40265-022-01773-5
Young JJ, Kopansky-Giles D, Ammendolia C. Multimodal non-surgical intervention for individuals with knee osteoarthritis:a retrospective case series. J Can Chiropr Assoc. 2019;63(2):92-9.
Yan L, Li D, Xing D, Fan Z, Du G, Jiu J, et al. Comparative efficacy and safety of exercise modalities in knee osteoarthritis:systematic review and network meta-analysis. bmj. 2025;391:e085242. DOI: https://doi.org/10.1136/bmj-2025-085242
Umoh IO, Dos Reis HJ, de Oliveira AC. Molecular mechanisms linking osteoarthritis and Alzheimer’s disease:shared pathways, mechanisms and breakthrough prospects. Int J Mol Sci. 2024;25(5):3044. DOI: https://doi.org/10.3390/ijms25053044
Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health:updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007;39(8):1423-34. DOI: https://doi.org/10.1249/mss.0b013e3180616b27
Balban MY, Neri E, Kogon MM, Weed L, Nouriani B, Jo B, et al. Brief structured respiration practices enhance mood and reduce physiological arousal. Cell Reports Med. 2023;4(1):100895. DOI: https://doi.org/10.1016/j.xcrm.2022.100895
Kang ES, Yook JS, Ha MS. Breathing exercises for improving cognitive function in patients with stroke. J Clin Med. 2022;11(10):2888. DOI: https://doi.org/10.3390/jcm11102888
Fincham GW, Strauss C, Montero-Marin J, Cavanagh K. Effect of breathwork on stress and mental health:A meta-analysis of randomised-controlled trials. Scientific Reports. 2023;13(1):432. DOI: https://doi.org/10.1038/s41598-022-27247-y
Pujari V, Parvathisam S. Breathing Your Way To Better Brain Function:The Role Of Respiration In Cognitive Performance. Journal of Pharmaceutical Negative Results. 2022;13(7):8214-9.
Shimada H, Makizako H, Doi T, Park H, Tsutsumimoto K, Verghese J, et al. Effects of combined physical and cognitive exercises on cognition and mobility in patients with mild cognitive impairment:a randomized clinical trial. J Am Med Dir Assoc. 2018;19(7):584-91. DOI: https://doi.org/10.1016/j.jamda.2017.09.019
Zeng CY, Zhang ZR, Tang ZM, Hua FZ. Benefits and mechanisms of exercise training for knee osteoarthritis. Front physiol. 2021;12:794062. DOI: https://doi.org/10.3389/fphys.2021.794062
Larsen KL, Brilla LR, McLaughlin WL, Li Y. Effect of Deep Slow Breathing on Pain‐Related Variables in Osteoarthritis. Pain Res Manag. 2019;2019(1):5487050. DOI: https://doi.org/10.1155/2019/5487050
Ferreira L, Tanaka K, Santos-Galduróz RF, Galduróz JC. Respiratory training as strategy to prevent cognitive decline in aging:a randomized controlled trial. Clin interv aging. 2015;10:593-603. DOI: https://doi.org/10.2147/CIA.S79560
Patel M, Hasoon J, Diez Tafur R, Lo Bianco G, Abd-Elsayed A. The Impact of Chronic Pain on Cognitive Function. Brain Sci. 2025;15(6):559. DOI: https://doi.org/10.3390/brainsci15060559
Lin G, Lan F, Wu D, Cao G, Li Z, Qi Z, et al. Resting-state functional connectivity alteration in elderly patients with knee osteoarthritis and declined cognition:An observational study. Front Aging Neurosci. 2022;14:1002642. DOI: https://doi.org/10.3389/fnagi.2022.1002642
Johnson AJ, Buchanan T, Laffitte Nodarse C, Valdes Hernandez PA, Huo Z, Cole JH, et al. Cross-sectional brain-predicted age differences in community-dwelling middle-aged and older adults with high impact knee pain. J Pain Res. 2022;15:3575-87. DOI: https://doi.org/10.2147/JPR.S384229
Heck DH, Correia BL, Fox MB, Liu Y, Allen M, Varga S. Recent insights into respiratory modulation of brain activity offer new perspectives on cognition and emotion. Biol psychol. 2022;170:108316. DOI: https://doi.org/10.1016/j.biopsycho.2022.108316
Downloads
Published
How to Cite
Issue
Section
