Skip to main content
NCBI home page
Medical Gas Research logoLink to Medical Gas Research
. 2026 Jan 6;16(3):258–262. doi: 10.4103/mgr.MEDGASRES-D-25-00116

Cognitive impairment in chronic respiratory disease patients using long-term oxygen therapy: a narrative review

Hiroki Annaka 1,*
PMCID: PMC12935113  PMID: 41496302

Abstract

Long-term oxygen therapy is used to treat of chronic respiratory diseases with chronic hypoxia. To date, long-term oxygen therapy has significantly contributed to the relief of dyspnea in the daily life of patients with chronic respiratory disease and chronic hypoxemia. Chronic hypoxia is a possible cause of cognitive impairment, and patients with chronic respiratory disease using long-term oxygen therapy with severe chronic hypoxia may be at a higher risk of cognitive impairment than patients using non-long-term oxygen therapy. Cognitive impairment in patients with chronic respiratory disease can lead to a decline in treatment adherence, including medication usage, health care check-ups, and smoking cessation efforts, which contribute to disease progression. In addition, patients using long-term oxygen therapy require oxygen delivery equipment. Operating oxygen delivery equipment is difficult for patients with cognitive impairment, and the inability to use long-term oxygen therapy properly is a serious challenge that can affect their life expectancy. Patients with chronic respiratory disease who use long-term oxygen therapy may be more affected by cognitive impairment than non-long-term oxygen therapy patients. Several review articles have addressed cognitive impairment in patients with chronic respiratory disease; however, none specifically focus on patients with chronic respiratory disease using long-term oxygen therapy. This narrative review describes the current knowledge and future issues regarding cognitive impairment in patients with chronic respiratory disease using the long-term oxygen therapy.

Keywords: cannula tubes, healthcare, hypoxemia, hypoxia, inflammation, lung function, medication, oxygen, pulmonary disease, smoking

Introduction

Long-term oxygen therapy (LTOT) involves the treatment of patients with chronic hypoxemia who require oxygen inhalation for at least 15 hours per day. This treatment was first reported in 1967,1 and two RCTs in the 1980s demonstrated its efficacy in prolonging the survival of patients with chronic respiratory disease (CRD) and hypoxemia.2,3 The development of oxygen delivery equipment facilitates the continuation of oxygen inhalation at home and promotes its widespread use of this therapy.4,5 To date, LTOT has significantly contributed to the relief of dyspnea in the daily life of patients with CRD and chronic hypoxemia.

Cognitive impairment is widely known to be a common comorbidity among patients with CRD. Cognitive impairment may be caused by multiple factors, which may vary among each patient.6,7 Among these, chronic hypoxemia is the most challenging.8,9 Recent studies have elucidated the mechanisms through which hypoxia leads to neuronal damage.10,11,12 Neuronal damage induced by hypoxia is thought to involve three key mechanisms: (1) inhibition of synaptophysin synthesis, (2) induction of inflammation and oxidative stress via the release of proinflammatory cytokines and reactive oxygen species, and (3) endothelial dysfunction and impaired cerebral blood flow due to activation of endothelial nitric oxide synthase.10,11,12 Furthermore, hypoxemia is associated with a decline in lung function, including unfavorable changes in parameters such as forced expiratory volume in 1 second, forced vital capacity, and diffusing capacity for carbon monoxide, and a decrease in oxygen supply to the brain.8,9 This condition poses a threat to the brain due to the physiological stress caused by inflammatory mediators.13 As a result, it leads to cognitive impairment due to organic brain damage.14 Decreased lung function and severe hypoxemia are associated with a higher risk of dementia and severe cognitive impairment. This hypothesis is supported by large cohort studies15,16 and meta-analyses.14,17 The most important concern regarding cognitive impairment is its negative impact on the treatment of patients with CRD.18 It may reduce adherence to treatment and contribute to disease progression.18,19 Therefore, cognitive impairment in CRD is a critical factor to consider when planning a patient’s treatment plan.20,21

Patients with CRD using LTOT have exhibited specific characteristics compared to non-LTOT patients. One example is severe hypoxia in the absence of oxygen inhalation.5,22 Another is the lifestyle adjustment required to coexist with oxygen delivery equipment and cannula tubes.23,24,25 These unique characteristics of CRD patients using LTOT, such as severity and lifestyle, may differ from those of non-LTOT patients in terms of the negative effects of cognitive impairment.

Unfortunately, while a few review articles address cognitive impairment in CRD patients generally, no review articles to date have focused specifically on CRD patients using LTOT. Furthermore, many existing review articles primarily examine the mechanisms underlying cognitive impairment in patients with CRD, such as hypoxemia, while providing limited insight into the specific characteristics of cognitive impairment in those using LTOT and its potential impact on patient’s outcomes and prognosis. Therefore, this narrative review summarizes current knowledge on cognitive impairment in patients with CRD using LTOT and offers directions for future research. Particular emphasis is placed on the effects of cognitive impairment on daily functioning and long-term prognosis in patients with CRD using LTOT.

Search Strategy

This study was searched using PubMed. The search used the following formula: “long-term oxygen therapy” AND “cognitive” AND “chronic respiratory disease.” All years were included in the search.

Cognitive Impairment in Chronic Respiratory Disease Patients using Long-Term Oxygen Therapy

According to the global strategy for prevention, diagnosis and management of COPD: 2025 report, the prevalence of cognitive impairment in chronic obstructive pulmonary disease (COPD) is approximately 36% or 56%, depending on cognitive function tests.26 This percentage includes patients with CRDs of all severities, including those without chronic hypoxia and those using LTOT.27,28 Our study, limited to patients with CRD using LTOT, showed a 70% prevalence of cognitive impairment, as measured by the Montreal Cognitive Assessment.29 Our results suggest that patients with CRD using LTOT may be at an increased risk of comorbid cognitive impairment. However, this cross-sectional study comprised data from a single center, which limits the generalizability of the results. Large-scale studies are warranted to investigate the prevalence of cognitive impairment in CRD patients using the LTOT.

Table 1 presents a summary of previous studies evaluating cognitive function in patients with CRD using LTOT. Several studies have compared the cognitive functions of patients with CRD using LTOT and those with CRD using non-LTOT. Mermit Çilingir et al.30 compared patients with acute exacerbation of COPD using LTOT to those of non-LTOT on the Mini-Mental State Examination and indicated significantly lower scores for those using LTOT. In a study of patients with idiopathic pulmonary fibrosis by Bors et al.,31 the severe idiopathic pulmonary fibrosis group using the LTOT performed poorly on the Trail Making Test, Stroop Test, Hopkins Language Learning Test, and Boston Naming Test compared to the mild-to-moderate group, including some patients using the LTOT. These two studies showed that patients using LTOT had a more severe decline in lung function, as measured by forced expiratory volume in 1 second, forced vital capacity, and diffusing capacity for carbon monoxide, than those who did not use LTOT. Karamanli et al.32 compared cognitive function, measured by the Montreal Cognitive Assessment and Mini-Mental State Examination, in patients with COPD using LTOT and those who did not use LTOT with comparable lung function and found that patients using LTOT performed better. Similarly, in a study by Dal Negro et al.,33 patients with COPD using LTOT showed better performance in Trail Making Test than COPD patients not using LTOT when they had comparable lung function. These results suggest that the cognitive function of patients with CRD using LTOT due to severe lung function decline is lower than that of non-LTOT patients with mild lung function decline but higher than that of non-LTOT patients with comparable lung function. One concern is whether LTOT is effective in preventing cognitive decline. In our one-year prospective cohort study of patients with CRD using LTOT, we observed progressive cognitive decline in 40% of the patients.34 In addition, Ohrui et al.35 reported similar results; however, interestingly, this study showed that cognitive decline progressed faster in women than in men. In other words, LTOT has the potential to slow the progression of cognitive decline in patients with CRD and chronic hypoxia but may not be sufficient to fully preserve cognitive function. Routine cognitive testing using LTOT may be required for patients with CRD to account for their progressive cognitive decline. This can help detect the early signs of cognitive decline and establish a care plan for patients with cognitive impairment.

Table 1.

Summary of studies assessing cognitive function in patients with chronic respiratory disease using long-term oxygen therapy

Design Subject Control Outcome Results Reference
Cross-sectional study Chronic respiratory disease on long-term oxygen therapy (n = 96) None Montreal Cognitive Assessment Sixty-seven patients (70%) had a Montreal Cognitive Assessment score of less than 24 points. Annaka et al.29
Case-control study Regular user long-term oxygen therapy dependent-COPD (n = 22) Nonuser long-term oxygen therapy dependent-COPD (n = 62) Mini-Mental State Examination Mini-Mental State Examination scores for regular long-term oxygen therapy dependent-COPD were lower than those for non-regular long-term oxygen therapy dependent-COPD (18.81 ± 3.65 scores, 24.9 ± 5.17 scores, P < 0.001). Mermit Çilingir et al.30
Case-control study Severe idiopathic pulmonary fibrosis (n = 12; Home O2 user = 12) Mild to moderate idiopathic pulmonary fibrosis (n = 34. Home O2 user = 21) Control (n = 15) Trail Making Test, Stroop Color Word Test, Hopkins Verbal Learning Test, Boston Naming Test Severe idiopathic pulmonary fibrosis patients had poorer cognitive function than mild idiopathic pulmonary fibrosis patients or controls (Trail Maling Test-A: mean 42.3 ± 12.9 s, mean 33.5 ± 10.0 s, 33.1 ± 9.8 s, P = 0.04; Trail Maling Test-B: mean 135.9 ± 69.4 s, mean 86.7 ± 34.9 s, 83.2 ± 35.4 s, P < 0.01; Stroop Color Word Test 2: 49 ± 18.8, 59 ± 11.0, 63 ± 10.1, P = 0.02; Stroop Color Word Test 3: 20 ± 11.7, 30 ± 9.3, 38 ± 10.1, P < 0.01; Hopkins Verbal Learning Test: 7.7 ± 2.4, 7.8 ± 2.3, 9.7 ± 1.7, P = 0.01; Boston Naming Test: 52.5 ± 5.4, 55.4 ± 3.3, 56.7 ± 2.5, P = 0.01). Bors et al.31
Case-control study Regular-user long-term oxygen therapy dependent-COPD (n = 21) Nonuser long-term oxygen therapy dependent-COPD (n = 24) Mini-Mental State Examination, Montreal Cognitive Assessment Mini-Mental State Examination and Montreal Cognitive Assessment were higher in regular long-term oxygen therapy dependent-COPD than in nonuser long-term oxygen therapy dependent-COPD (Mini-Mental State Examination: P = 0.014; Montreal Cognitive Assessment: P = 0.007). Karamanli et al.32
Case-control study COPD regularly used long-term oxygen therapy (n = 73) COPD only as needed long-term oxygen therapy (n = 73) Mini-Mental Status test, Clock Drawing test, Trial Making test COPD regularly used long-term oxygen therapy performed better on the Trail Making Test than COPD only as needed long-term oxygen therapy (Trail Making Test A: 132.2 ± 35.8 s, 155.3 ± 52.5 s, P = 0.012; Trail Making Test B: 332.1 ± 36.2 s, 344.2 ± 31.8 s, P = 0.001). Dal Negro et al.33
Prospective observational study Chronic respiratory disease undergoing long-term oxygen therapy (n = 55) None Montreal Cognitive Assessment Twenty-two patients (40%) showed cognitive decline as defined by the minimal clinically important difference in the Montreal Cognitive Assessment. Annaka et al.34
Cross-Sectional study Chronic respiratory disease with long-term domiciliary oxygen therapy (n = 135) Chronic respiratory disease with non-long-term domiciliary oxygen therapy (n = 718) Mini-Mental State Examination Mini-Mental State Examination scores showed that age-related cognitive decline was more pronounced in female patients than in female controls (-0.524/year, R2 = 0.426, -0.120/year, R2 = 0.027, P < 0.0001). Ohrui et al.35
Open in a new tab

COPD: Chronic obstructive pulmonary disease.

However, most studies examining cognitive impairment in patients with CRD using LTOT should be interpreted with caution, as they often rely on small sample sizes from single-centers or non-randomized case-control designs.

Effects of Cognitive Impairment in Chronic Respiratory Disease Patients using Long-Term Oxygen Therapy

The effects of cognitive impairment on CRD patients include a decline in medication adherence,36 difficulty in operating inhalers,18 a decline in adherence to health care,37 and decreased smoking cessation rates.38 These effects cause frequent exacerbations resulting in disease progression.

Unlike non-LTOT patients, CRD patients using LTOT are required to operate oxygen delivery equipment in their daily lives. Adherence to LTOT remains suboptimal. A review by Katsenos et al.,39 reported that 30–55% of patients failed to adhere to prescribed LTOT regimes. Low adherence has been attributed, in part, to the complexity of operating oxygen supply equipment, which involves multiple procedural steps and may be particularly challenging for CRD patients with cognitive impairment.39,40,41 Specific processes that are made difficult by cognitive impairment include (1) keeping the oxygen supply equipment away from fire, (2) setting a predetermined oxygen flow, (3) switching to an external cylinder or equipment, (4) handling the cannula tube and oxygen supply equipment, (5) responding to alarm activation, and (6) difficulty in fitting the cannula tube.40,42,43 Gauthier et al.41 identified age as a predictor of adherence to LTOT. In our previous study, we evaluated the ability of patients with normal cognitive function and those with mild cognitive impairment to self-manage the operation of oxygen delivery equipment.40 The results revealed that patients with mild cognitive impairment demonstrated significantly lower self-management ability for oxygen supply equipment compared to those with normal cognitive function. Furthermore, lower scores on the Montreal Cognitive Assessment were associated with a reduced ability to independently operate the equipment.40 This can result in fires, explosions, falls, and inadequate oxygen inhalation.40,42,43 Cognitive impairment is also associated with increased sedentary time in CRD patients using LTOT.29 This may be due to the patient’s inability to successfully handle an extended oxygen tube for inhalation at home or external oxygen supply equipment, which limits the patient’s range of activities.25,29 Approximately 75% of patients experienced falls associated with oxygen delivery equipment, and fear of falling may contribute to increased sedentary behavior.29,43

Thus, the effects of cognitive impairment in CRD patients using LTOT may not only reduce adherence to treatment, as observed in CRD patients with non-LTOT, but may also render oxygen supply difficult. However, research exploring the relationship between cognitive impairment and the ability to self-manage LTOT in patients with CRD remains extremely limited. Moreover, existing studies are primarily small-sample cross-sectional investigations, highlighting the need for further in-depth research in this area.

Effects of Cognitive Impairment on Mortality in Patients with Chronic Respiratory Disease using Long-Term Oxygen Therapy

Older adults with mild cognitive impairment have higher mortality rates when CRD is a comorbid condition compared to healthy older adults.44 This has been shown to accelerate disease progression with exacerbations due to a decline in treatment adherence.44 Although studies on cardiovascular disease have provided evidence for the prognostic value of a decline in treatment adherence due to cognitive impairment, to the best of our knowledge, no studies have been conducted examining CRD in this context.45,46

Our previous study showed that cognitive function may predict 2-year mortality in patients with CRD using LTOT.47 The aforementioned challenges with the operation of oxygen supply equipment due to cognitive impairment are presumed to be factors affecting the life expectancy of patients with CRD using LTOT. Large-scale cohort studies have shown that LTOT use reduces the incidence of acute exacerbations and hospital readmission.48 These findings suggest that adherence to LTOT plays a beneficial role in slowing disease progression. Fires and explosions caused by placing the oxygen supply equipment near a fire can lead to accidental deaths.49 Falls due to contact with cannula tubes, oxygen delivery equipment, and inadequate oxygen inhalation lead to increased dyspnea and frequent hospitalizations in patients with CRD using LTOT, gradually leading to activity limitations and disease progression.50,51 Based on these considerations, cognitive impairment is not directly related to mortality but may be a factor that, in combination with other factors, accelerates the progression of CRD in patients using LTOT.47,48,49 Figure 1 shows the relationship between cognitive impairment and mortality in patients with CRD using LTOT, which can be explained by current knowledge.

Figure 1.

Figure 1

Open in a new tab

Effects of cognitive impairment in patients with chronic respiratory disease using long-term oxygen therapy (LTOT).

This figure shows the effect of cognitive impairment in chronic respiratory disease patients using LTOT and its relationship to mortality. The colored boxes show the effect specific to patients with chronic respiratory disease using LTOT that is not present in patients who do not use LTOT. Created with Microsoft PowerPoint.

Future Issues

As discussed in this narrative review, cognitive function in patients with CRD using LTOT is associated with many challenges that need to be addressed in the future.

The first challenge lies in understanding the characteristics of cognitive function in patients with CRD using LTOT. In non-LTOT CRD patients, specific cognitive functions, such as verbal memory and executive function, are impaired.28,52 In addition, COPD reduces dual-tasking ability, and if patients with CRD using LTOT also experience this impairment, it may lead to contact with oxygen delivery equipment and cannula tubing.53,54 Cognitive functioning in patients with CRD using the LTOT may be specifically impaired, and understanding these characteristics will greatly assist in planning support. For example, a healthcare provider instructing a patient on how to use equipment can provide written instructions for patients with memory impairments or hide unused buttons for patients with attention impairments. Second, we aimed to develop a predictive model for mortality in patients with CRD using the LTOT with added cognitive functions. Prospective cohort studies have identified dyspnea, BMI, exercise capacity, grip strength, and activities of daily living as predictors of mortality in patients with CRD using LTOT.47,55,56 We aim to test a predictive model that integrates these established predictors with cognitive function. This finding provides clues to elucidate how cognitive function interacts with other factors that affect mortality in patients with CRD using LTOT. Third, interventions for the prevention of cognitive impairment in patients with CRD using the LTOT. A report on post-coronavirus disease 2019 (COVID-19) changes showed that even with arterial blood oxygen saturation in the normal range, patients experienced brain hypoxia.57 Prevention of cognitive impairment may require setting the oxygen flow rate of the LTOT according to the brain tissue oxygen saturation. Cognitive training may also improve cognitive function for patients with CRD who use LTOT than those who do not use LTOT.58,59 Additionally, nasal oxygen inhalation has been shown to enhance neural oscillations and improve brain activity and cognitive performance.60,61 Specifically, this intervention amplifies gamma wave activity within the brain’s default mode network, thereby enhancing higher-order cognitive performance. Interventions that combine oxygen inhalation with cognitive training may offer a noninvasive and effective therapeutic approach for patients with CRD receiving LTOT. Cognitive training combined with exercise may be more effective in improving cognitive function,62,63 but patients with CRD using LTOT may experience hypoxia during exercise and should be cautious in its application.63 Recently, non-invasive brain stimulation has been applied in pulmonary rehabilitation and has the potential to help prevent cognitive impairment in patients with CRD.64 In a randomized clinical trial by Andrade et al.64 involving intensive care patients with coronavirus disease, the group receiving high-definition transcranial direct current stimulation experienced a shorter duration of delirium compared to the group receiving standard tDCS. The cognitive benefits of tDCS are attributed to its regulation of regional cerebral perfusion and the cortical excitatory effects induced by anodal stimulation.65,66 Cognitive training that does not require exercise and utilizes modern therapies such as noninvasive brain stimulation may benefit patients with CRD using LTOT. Cognitive training combined with either noninvasive brain stimulation or with nasal oxygen inhalation can target a wide range of cognitive domains and may enhance functions such as memory and attention. Finally, interventions need to be developed to enable patients with CRD and cognitive impairment to use LTOT appropriately. For example, for patients who have difficulty operating oxygen supply equipment, providing guidance to family members may be beneficial.22,67 Additionally, long-term post discharge support can be provided by incorporating a follow-up program for LTOT through home visits.68 Regular follow-ups after LTOT initiation may be an effective intervention for patients with CRD using LTOT and progressive cognitive decline. An educational program for LTOT in patients with cognitive impairment is expected to be developed and validated in the future.

These strategies can be categorized into three domains: prevention, cognitive improvement, and coping (Figure 2). Prevention involves early cognitive screening and the provision of adequate oxygen flow support to reduce the risk of cerebral hypoxia. Such interventions aim to prevent the onset of cognitive impairment. Cognitive interventions enhance cognitive function through training combined with noninvasive brain stimulation and nasal oxygen inhalation. Coping strategies include educational programs for patients and their families, along with follow-up support to ensure sustained adherence to LTOT. These interventions aim to ensure that patients with cognitive impairment consistently use LTOT as prescribed. The selection of prevention, cognitive improvement, and coping strategies should be tailored to the patient’s level of cognitive function.

Figure 2.

Figure 2

Open in a new tab

Intervention strategies based on cognitive function in patients with chronic respiratory disease using long-term oxygen therapy.

Prevention strategies are recommended for patients with normal cognitive function; cognitive improvement approaches are suitable for those with mild cognitive impairment; and coping strategies are intended for patients with more advanced cognitive impairment. Created with Microsoft PowerPoint.

Conclusion

This narrative review presents the current knowledge on cognitive impairment in patients with CRD using LTOT. Cognitive function in patients with CRD using LTOT is better preserved than that in patients not using LTOT with comparable respiratory function or hypoxemia but may be worse than that in patients with mildly impaired respiratory function. Cognitive impairment may make it difficult for patients to operate LTOT equipment, which is their lifeline, resulting in a poor prognosis for this patient population.

However, several challenges remain in this research area. In particular, there is an urgent need to investigate strategies to prevent the progression of cognitive decline in patients with CRD using LTOT and develop supportive strategies for this patient population with impaired cognitive function. A more definitive understanding of the relationship between LTOT and cognitive impairment in patients with CRDs would be an important step in addressing this issue.

Footnotes

Conflicts of interest: The author declares no conflicts of interest.

Declaration of AI and AI-assisted technologies in the writing process: The author declares that no Generative AI was used in the preparation of this manuscript.

Data availability statement:

All relevant data are within the paper.

References

  • 1.Levine BE, Bigelow DB, Hamstra RD, et al. The role of long-term continuous oxygen administration in patients with chronic airway obstruction with hypoxemia. Ann Intern Med. 1967;66:639–650. doi: 10.7326/0003-4819-66-4-639. [DOI] [PubMed] [Google Scholar]
  • 2.No authors listed. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93:391–398. doi: 10.7326/0003-4819-93-3-391. [DOI] [PubMed] [Google Scholar]
  • 3.No authors listed. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981;1:681–686. [PubMed] [Google Scholar]
  • 4.Branson RD, King A, Giordano SP. Home oxygen therapy devices: providing the prescription. Respir Care. 2019;64:230–232. doi: 10.4187/respcare.06850. [DOI] [PubMed] [Google Scholar]
  • 5.Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202:e121–141. doi: 10.1164/rccm.202009-3608ST. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Dodd JW, Getov SV, Jones PW. Cognitive function in COPD. Eur Respir J. 2010;35:913–922. doi: 10.1183/09031936.00125109. [DOI] [PubMed] [Google Scholar]
  • 7.Dodd JW. Lung disease as a determinant of cognitive decline and dementia. Alzheimers Res Ther. 2015;7:32. doi: 10.1186/s13195-015-0116-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Wang X, Cui L, Ji X. Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms. Metab Brain Dis. 2022;37:51–66. doi: 10.1007/s11011-021-00796-3. [DOI] [PubMed] [Google Scholar]
  • 9.Higbee DH, Dodd JW. Cognitive impairment in COPD: an often overlooked co-morbidity. Expert Rev Respir Med. 2021;15:9–11. doi: 10.1080/17476348.2020.1811090. [DOI] [PubMed] [Google Scholar]
  • 10.Chen A, Teng C, Wei J, et al. Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia. Gut Microbes. 2025;17:2471015. doi: 10.1080/19490976.2025.2471015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Zhang X, Xu H, Yin S, Gozal D, Khalyfa A. Obstructive sleep apnea and memory impairments: clinical characterization, treatment strategies, and mechanisms. Sleep Med Rev. 2025;81:102092. doi: 10.1016/j.smrv.2025.102092. [DOI] [PubMed] [Google Scholar]
  • 12.Jia NN, Yao MF, Zhu CX, et al. Chronic intermittent hypoxia-induced neural injury: pathophysiology, neurodegenerative implications, and therapeutic insights. CNS Neurosci Ther. 2025;31:e70384. doi: 10.1111/cns.70384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.McKenna HT, Murray AJ, Martin DS. Human adaptation to hypoxia in critical illness. J Appl Physiol. 2020;129:656–663. doi: 10.1152/japplphysiol.00818.2019. [DOI] [PubMed] [Google Scholar]
  • 14.Russ TC, Kivimäki M, Batty GD. Respiratory disease and lower pulmonary function as risk factors for dementia: a systematic review with meta-analysis. Chest. 2020;157:1538–1558. doi: 10.1016/j.chest.2019.12.012. [DOI] [PubMed] [Google Scholar]
  • 15.Wang J, Dove A, Song R, et al. Poor pulmonary function is associated with mild cognitive impairment, its progression to dementia, and brain pathologies: a community-based cohort study. Alzheimers Dement. 2022;18:2551–2559. doi: 10.1002/alz.12625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Lutsey PL, Chen N, Mirabelli MC, et al. Impaired lung function, lung disease, and risk of incident dementia. Am J Respir Crit Care Med. 2019;199:1385–1396. doi: 10.1164/rccm.201807-1220OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Li QY, Li XM, Hu HY, et al. Associations of lung function decline with risks of cognitive impairment and dementia: a meta-analysis and systematic review. J Alzheimers Dis. 2023;92:853–873. doi: 10.3233/JAD-221136. [DOI] [PubMed] [Google Scholar]
  • 18.Baird C, Lovell J, Johnson M, Shiell K, Ibrahim JE. The impact of cognitive impairment on self-management in chronic obstructive pulmonary disease: a systematic review. Respir Med. 2017;129:130–139. doi: 10.1016/j.rmed.2017.06.006. [DOI] [PubMed] [Google Scholar]
  • 19.Chang SS, Chen S, McAvay GJ, Tinetti ME. Effect of coexisting chronic obstructive pulmonary disease and cognitive impairment on health outcomes in older adults. J Am Geriatr Soc. 2012;60:1839–1846. doi: 10.1111/j.1532-5415.2012.04171.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Mendes M, Rodrigues GJD, Spruit M, Marques A. Understanding the determinants and outcomes of education in pulmonary rehabilitation: moving towards person-centered care. Chest. 2025;167:1615–1627. doi: 10.1016/j.chest.2025.01.005. [DOI] [PubMed] [Google Scholar]
  • 21.Rozenberg D, Reid WD, Camp P, et al. Translating the interplay of cognition and physical performance in COPD and interstitial lung disease: meeting report and literature review. Chest. 2024;166:721–732. doi: 10.1016/j.chest.2024.05.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Khor YH, Renzoni EA, Visca D, McDonald CF, Goh NSL. Oxygen therapy in COPD and interstitial lung disease: navigating the knowns and unknowns. ERJ Open Res. 2019;5:00118–2019. doi: 10.1183/23120541.00118-2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Kampelmacher MJ, van Kestern RG, Alsbach GP, et al. Characteristics and complaints of patients prescribed long-term oxygen therapy in The Netherlands. Respir Med. 1998;92:70–75. doi: 10.1016/s0954-6111(98)90035-x. [DOI] [PubMed] [Google Scholar]
  • 24.Cullen DL, Stiffler D. Long-term oxygen therapy: review from the patients’ perspective. Chron Respir Dis. 2009;6:141–147. doi: 10.1177/1479972309103046. [DOI] [PubMed] [Google Scholar]
  • 25.Cani KC, Matte DL, Silva IJCS, Gulart AA, Karloh M, Mayer AF. Impact of home oxygen therapy on the level of physical activities in daily life in subjects with COPD. Respir Care. 2019;64:1392–1400. doi: 10.4187/respcare.06206. [DOI] [PubMed] [Google Scholar]
  • 26.Global strategy for prevention, diagnosis and management of COPD: 2025 Report. Global Initiative for Chronic Obstructive Lung Disease. https://goldcopd.org/2025-gold-report/ . Accessed July 8, 2025.
  • 27.Yohannes AM, Chen W, Moga AM, Leroi I, Connolly MJ. Cognitive impairment in chronic obstructive pulmonary disease and chronic heart failure: a systematic review and meta-analysis of observational studies. J Am Med Dir Assoc. 2017;18:451. doi: 10.1016/j.jamda.2017.01.014. [DOI] [PubMed] [Google Scholar]
  • 28.Cleutjens FA, Franssen FM, Spruit MA, et al. Domain-specific cognitive impairment in patients with COPD and control subjects. Int J Chron Obstruct Pulmon Dis. 2016;12:1–11. doi: 10.2147/COPD.S119633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Annaka H, Nomura T, Moriyama H. Sedentary time and cognitive impairment in patients using long-term oxygen therapy: a cross-sectional study. Int J Environ Res Public Health. 2022;19:1726. doi: 10.3390/ijerph19031726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Mermit Çilingir B, Günbatar H, Çilingir V. Cognitive dysfunction among patients in chronic obstructive pulmonary disease: effects of exacerbation and long-term oxygen therapy. Clin Respir J. 2020;14:1137–1143. doi: 10.1111/crj.13250. [DOI] [PubMed] [Google Scholar]
  • 31.Bors M, Tomic R, Perlman DM, Kim HJ, Whelan TP. Cognitive function in idiopathic pulmonary fibrosis. Chron Respir Dis. 2015;12:365–372. doi: 10.1177/1479972315603552. [DOI] [PubMed] [Google Scholar]
  • 32.Karamanli H, Ilik F, Kayhan F, Pazarli AC. Assessment of cognitive impairment in long-term oxygen therapy-dependent COPD patients. Int J Chron Obstruct Pulmon Dis. 2015;10:2087–2094. doi: 10.2147/COPD.S88326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Dal Negro RW, Bonadiman L, Bricolo FP, Tognella S, Turco P. Cognitive dysfunction in severe chronic obstructive pulmonary disease (COPD) with or without long-term oxygen therapy (LTOT) Multidiscip Respir Med. 2015;10:17. doi: 10.1186/s40248-015-0013-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Annaka H, Nomura T, Moriyama H. Association between cognitive decline and activities of daily living decline in patients undergoing long-term oxygen therapy: a prospective observational pilot study. Disabil Rehabil. 2023;45:3493–3499. doi: 10.1080/09638288.2022.2127934. [DOI] [PubMed] [Google Scholar]
  • 35.Ohrui T, Tanaka K, Chiba K, et al. Cognitive decline in patients with long-term domiciliary oxygen therapy. Tohoku J Exp Med. 2005;206:347–352. doi: 10.1620/tjem.206.347. [DOI] [PubMed] [Google Scholar]
  • 36.O’Conor R, Muellers K, Arvanitis M, et al. Effects of health literacy and cognitive abilities on COPD self-management behaviors: a prospective cohort study. Respir Med. 2019;160:105630. doi: 10.1016/j.rmed.2019.02.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Pierobon A, Sini Bottelli E, Ranzini L, et al. COPD patients’ self-reported adherence, psychosocial factors and mild cognitive impairment in pulmonary rehabilitation. Int J Chron Obstruct Pulmon Dis. 2017;12:2059–2067. doi: 10.2147/COPD.S133586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Brega AG, Grigsby J, Kooken R, Hamman RF, Baxter J. The impact of executive cognitive functioning on rates of smoking cessation in the San Luis Valley Health and Aging Study. Age Ageing. 2008;37:521–525. doi: 10.1093/ageing/afn121. [DOI] [PubMed] [Google Scholar]
  • 39.Katsenos S, Constantopoulos SH. Long-term oxygen therapy in COPD: factors affecting and ways of improving patient compliance. Pulm Med. 2011;2011:325362. doi: 10.1155/2011/325362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Annaka H, Nomura T, Moriyama H. Cognitive function and the ability to operate long-term oxygen therapy equipment: an exploratory study. Int J Environ Res Public Health. 2022;19:10708. doi: 10.3390/ijerph191710708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Gauthier A, Bernard S, Bernard E, Simard S, Maltais F, Lacasse Y. Adherence to long-term oxygen therapy in patients with chronic obstructive pulmonary disease. Chron Respir Dis. 2019;16:1479972318767724. doi: 10.1177/1479972318767724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Moslander C, Lat T, Giri B, Pattison R, Coppin JD, Bhat UM. Long-term oxygen therapy and risk of fire-related events. Fed Pract. 2020;37:442–446. doi: 10.12788/fp.0048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Björklund F, Ekström M. Adverse effects, smoking, alcohol consumption, and quality of life during long-term oxygen therapy: a nationwide study. Ann Am Thorac Soc. 2022;19:1677–1686. doi: 10.1513/AnnalsATS.202110-1174OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Bae JB, Han JW, Kwak KP, et al. Impact of mild cognitive impairment on mortality and cause of death in the elderly. J Alzheimers Dis. 2018;64:607–616. doi: 10.3233/JAD-171182. [DOI] [PubMed] [Google Scholar]
  • 45.Kewcharoen J, Prasitlumkum N, Kanitsoraphan C, et al. Cognitive impairment associated with increased mortality rate in patients with heart failure: a systematic review and meta-analysis. J Saudi Heart Assoc. 2019;31:170–178. doi: 10.1016/j.jsha.2019.06.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Fang Z, Zhang Q. Association between cognitive impairment and cardiovascular mortality in mature and older adults: a meta-analysis. Exp Gerontol. 2024;192:112440. doi: 10.1016/j.exger.2024.112440. [DOI] [PubMed] [Google Scholar]
  • 47.Annaka H, Nomura T, Moriyama H. Predictors of 2-year mortality in patients receiving long-term oxygen therapy: a prospective observational study. J Palliat Med. 2024;27:495–502. doi: 10.1089/jpm.2023.0505. [DOI] [PubMed] [Google Scholar]
  • 48.Khor YH, Palm A, Wong AW, et al. Effects of long-term oxygen therapy on acute exacerbation and hospital burden: the national DISCOVERY study. Thorax. 2025;80:378–384. doi: 10.1136/thorax-2023-221063. [DOI] [PubMed] [Google Scholar]
  • 49.Banerjee S, Khubchandani J, England-Kennedy E, McIntyre R, Kopera-Frye K, Batra K. Cognitive functioning influences mortality risk among older adults with COPD. Healthcare (Basel) 2024;12:2220. doi: 10.3390/healthcare12222220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Tanash HA, Ringbaek T, Huss F, Ekström M. Burn injury during long-term oxygen therapy in Denmark and Sweden: the potential role of smoking. Int J Chron Obstruct Pulmon Dis. 2017;12:193–197. doi: 10.2147/COPD.S119949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Semasinghe Bandaralage SP, Denniss AR, Syed M, Sriram KB. Long-term oxygen therapy-related adverse outcomes resulting in hospitalisation: 3-year experience of an Australian metropolitan health service. Intern Med J. 2019;49:1435–1437. doi: 10.1111/imj.14633. [DOI] [PubMed] [Google Scholar]
  • 52.Annaka H, Nomura T, Moriyama H. Cognitive function in patients with mild idiopathic pulmonary fibrosis: a case-control pilot study. Occup Ther Health Care. 2025;39:397–411. doi: 10.1080/07380577.2024.2324256. [DOI] [PubMed] [Google Scholar]
  • 53.Pasten JG, Aguayo JC, Aburto J, et al. Dual-task performance in individuals with chronic obstructive pulmonary disease: a systematic review with meta-analysis. Pulm Med. 2024;2024:1230287. doi: 10.1155/2024/1230287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Alexandru Florian C, Camelia Corina P, Adelina M, et al. Dual-task performance and balance in patients with severe COPD: a cross-sectional study. Ther Adv Respir Dis. 2024;18:17534666241287302. doi: 10.1177/17534666241287302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Marti S, Muñoz X, Rios J, Morell F, Ferrer J. Body weight and comorbidity predict mortality in COPD patients treated with oxygen therapy. Eur Respir J. 2006;27:689–696. doi: 10.1183/09031936.06.00076405. [DOI] [PubMed] [Google Scholar]
  • 56.Björklund F, Palm A, Gorani JA, et al. Breathlessness and exercise performance to predict mortality in long-term oxygen therapy - the population-based DISCOVERY study. Respir Med. 2023;216:107306. doi: 10.1016/j.rmed.2023.107306. [DOI] [PubMed] [Google Scholar]
  • 57.Adingupu DD, Soroush A, Hansen A, Twomey R, Dunn JF. Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19. J Neurol. 2023;270:3303–3314. doi: 10.1007/s00415-023-11767-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.van Beers M, Mount SW, Houben K, et al. Working memory training efficacy in COPD: the randomised, double-blind, placebo-controlled Cogtrain trial. ERJ Open Res. 2021;7:00475–2021. doi: 10.1183/23120541.00475-2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Rassam P, Pazzianotto-Forti EM, Matsumura U, et al. Impact of cognitive capacity on physical performance in chronic obstructive pulmonary disease patients: a scoping review. Chron Respir Dis. 2023;20:14799731231163874. doi: 10.1177/14799731231163874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Salimi M, Ayene F, Parsazadegan T, Nazari M, Jamali Y, Raoufy MR. Nasal airflow promotes default mode network activity. Respir Physiol Neurobiol. 2023;307:103981. doi: 10.1016/j.resp.2022.103981. [DOI] [PubMed] [Google Scholar]
  • 61.Salimi M, Javadi AH, Nazari M, et al. Nasal air puff promotes default mode network activity in mechanically ventilated comatose patients: a noninvasive brain stimulation approach. Neuromodulation. 2022;25:1351–1363. doi: 10.1016/j.neurom.2021.11.003. [DOI] [PubMed] [Google Scholar]
  • 62.Tabka O, Sanaa I, Mekki M, Acheche A, Paillard T, Trabelsi Y. Effect of a pulmonary rehabilitation program combined with cognitive training on exercise tolerance and cognitive functions among Tunisian male patients with chronic obstructive pulmonary disease: a randomized controlled trial. Chron Respir Dis. 2023;20:14799731231201643. doi: 10.1177/14799731231201643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Ward SA, Grocott MPW, Levett DZH. Exercise testing, supplemental oxygen, and hypoxia. Ann Am Thorac Soc. 2017;14:S140–148. doi: 10.1513/AnnalsATS.201701-043OT. [DOI] [PubMed] [Google Scholar]
  • 64.Andrade SM, Cecília de Araújo Silvestre M, Tenório de França EÉ, et al. Efficacy and safety of HD-tDCS and respiratory rehabilitation for critically ill patients with COVID-19 The HD-RECOVERY randomized clinical trial. Brain Stimul. 2022;15:780–788. doi: 10.1016/j.brs.2022.05.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Figeys M, Zeeman M, Kim ES. Effects of transcranial direct current stimulation (tDCS) on cognitive performance and cerebral oxygen hemodynamics: a systematic review. Front Hum Neurosci. 2021;15:623315. doi: 10.3389/fnhum.2021.623315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Müller D, Habel U, Brodkin ES, Weidler C. High-definition transcranial direct current stimulation (HD-tDCS) for the enhancement of working memory - A systematic review and meta-analysis of healthy adults. Brain Stimul. 2022;15:1475–1485. doi: 10.1016/j.brs.2022.11.001. [DOI] [PubMed] [Google Scholar]
  • 67.Katsenos S, Constantopoulos SH. Long-term oxygen therapy in COPD: factors affecting and ways of improving patient compliance. Pulm Med. 2011;2011:325362. doi: 10.1155/2011/325362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Lacasse Y, Bernard S, Maltais F, Nguyen VH. Cost-effectiveness of an extended home visit program for oxygen-dependent COPD patients. Respir Care. 2022;67:1082–1090. doi: 10.4187/respcare.09781. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

All relevant data are within the paper.

Articles from Medical Gas Research are provided here courtesy of Wolters Kluwer -- Medknow Publications

RESOURCES