Links between nocturnal hypoxia and cognitive function in breast cancer

Links between nocturnal hypoxia and cognitive function in breast cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Links between nocturnal hypoxia and cognitive function in breast cancer Clara Elia, Joy Perrier, Mylène Duivon, Stéphane Rehel, François Gernier, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6016528/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Nov, 2025 Read the published version in Scientific Reports → Version 1 posted 6 You are reading this latest preprint version Abstract Cognitive complaints are common in breast cancer (BC). Previous studies have linked sleep-disordered breathing (SDB) to cognitive decline in the general population, highlighting hypoxia as a key factor in cognitive decline severity. This link is understudied in BC patients. We investigated the association between nocturnal hypoxia and cognitive performance in 35 BC patients compared to 21 healthy controls (HC; mean ages: 61.6 ± 5.3 and 62.6 ± 4.3, respectively) using in-home ambulatory polysomnography, including oximeter to record oxygen saturation. All participants completed questionnaires and cognitive tests. Non-parametric Wilcoxon tests were conducted to compare the two groups and multivariable models to measure the association between hypoxia and cognitive performance, adjusting for anxiety and depression. Our results showed more frequent nocturnal hypoxia and more cognitive complaints in BC patients compared to HCs ( p <0.05). However, cognitive tests did not show significant impairment in the BC group, and no significant association was found between nocturnal hypoxia and cognitive performance. Our patients were treated with radiotherapy and/or endocrine therapy, but without chemotherapy, which may explain their normal cognitive scores despite subjective cognitive complaints. Nocturnal hypoxia is more prevalent in BC patients than in HCs, but it may not be the primary factor influencing cognitive performance in this population. Trial Registration NCT03420105, registered: January 10, 2018 Biological sciences/Cancer/Breast cancer Biological sciences/Cancer/Cancer therapy Biological sciences/Cancer Biological sciences/Psychology hypoxia sleep disturbances breast cancer cognitive function cancer-related cognitive impairments Figures Figure 1 Introduction Cognitive deficits in cancer, often referred to as “cancer-related cognitive impairments” (CRCI), are commonly reported by breast cancer (BC) patients. CRCI are mainly subtle in nature and concern difficulties in memory, attention, executive functions, and processing speed (1–3). Despite their subtle nature, these impairments can persist (4) and negatively impact the quality of life of BC patients, hindering their ability to return to work and resume daily activities (5,6). Cognitive complaints are frequently reported by BC patients following chemotherapy (7,8), and some studies also suggest an exacerbation of cognitive complaints among BC women undergoing endocrine therapy (ET) (9,10). Besides cancer treatments, other factors such as age, psycho-affective and medical comorbidities, and sleep disorders can also contribute to the occurrence and persistence of cognitive decline in BC (11–16). Notably, self-reported sleep difficulties were found to be strongly associated with CRCI (12,17), and many BC patients express sleep difficulties (13,18,19). One of the most commonly reported symptoms of sleep disturbances in BC patients is sleep-disordered breathing (SDB) (20). Specifically, SDB is a syndrome characterized by upper airway dysfunction during sleep, marked by snoring, heightened respiratory effort caused by increased resistance in the upper airway, and the tendency of the pharynx to collapse (21,22). The primary consequences of SDB are nocturnal hypoxia and sleep fragmentation (23). Interest in exploring the prevalence of SDB in BC patients has grown recently, marked by the initiation of a first study in 2021, which used polysomnography (PSG) in BC patients treated with chemotherapy, radiotherapy (RT) and/or ET (24). This study found an 88% prevalence of SDB in BC patients. It is important to note, however, that the study did not compare its results to a control group. Individuals without cancer experiencing SDB often demonstrate cognitive difficulties (25–27), particularly affecting memory, executive functions, and attention (28). Additionally, numerous studies have confirmed an association between SDB and cognitive decline in older adults (25,29–32). Hypoxia refers to a condition characterized by a reduced intake of oxygen or an impaired ability of oxygen use (33). Since the brain depends on an important oxygen supply to assure neuronal connectivity and synaptic activity (34), oxygen deprivation can lead to cognitive dysfunction (35). A recent literature review concluded that hypoxia is the primary contributor to cognitive dysfunction in elderly patients (29). Similarly, a study by Yaffe and colleagues (31) found that nocturnal hypoxia was more commonly associated with cognitive decline than other sleep-related disturbances. While sleep fragmentation and nocturnal hypoxia often co-occur in SDB, sleep fragmentation primarily impacts cognition through secondary mechanisms such as increased daytime sleepiness and reduced vigilance (36). In the 2011 study by Yaffe and colleagues (31), no association was found between sleep fragmentation and cognitive impairment, further supporting the dominant role of nocturnal hypoxia in cognitive decline. Despite the presence of cognitive impairment in BC, and despite evidence linking hypoxia to cognitive impairment in the general population, this link has yet to be explored in BC. This highlights a significant gap in the available data, hindering the effective management of hypoxia and, as a result, limiting the potential to improve patients’ quality of life. The current study aims to characterize the presence of nocturnal hypoxia and its association with cognitive functioning in BC patients compared to HCs. By investigating the relationship between hypoxia and CRCI, we hypothesize that nocturnal hypoxia will be linked to cognitive impairment in BC patients. Results Clinical and demographic characteristics of the sample The demographic and clinical characteristics of the participants are provided in Table 1 . No significant differences were observed between BC patients and HCs in terms of demographic characteristics or depression ( p s > 0.05). However, a significant difference was observed on the state anxiety as measured by STAI-A ( p = 0.02). Table 1 Demographic (mean ± SD [range]) and clinical ( n (%)) characteristics, and self-reported outcomes of HCs and BC patients. P values ≤ 0.05 are in bold Characteristics HCs (n = 21) BC (n = 35) p-value Demographic Age (years) 62.2 ± 4.1 [ 54 – 69 ] 61.6 ± 5.3 [ 51 – 69 ] 0.71 Education (years) 11.5 ± 2.2 [ 7 – 16 ] 12.0 ± 3.0 [ 6 – 17 ] 0.56 Clinical Cancer stage, n (%): 0, I, IIA - 17 (53), 13 (38), 5 (9) Surgery, n (%): Tumorectomy, Mastectomy, Both - 30 (86), 4 (11), 1 (3) Endocrine therapy (ET), n (%): Treated with, not treated with ET - 18 (51), 17 (49) Time since diagnosis (months) - 13.4 ± 3.14 Self-reported measures Depression (BDI) 3.8 ± 3.1 [0–13] 3.3 ± 3.2 [0–14] 0.38 State Anxiety (STAI-A) 44.43 ± 14.83 [24–78] 35.65 ± 11.75 [ 20 – 72 ] 0.02 Trait Anxiety (STAI-B) Insomnia Severity Index (ISI) Sleep quality (PSQI) 42.3 ± 9.5 [ 26 – 68 ] 6.7 ± 4.0 [0–16] 5.5 ± 2.8 [ 1 – 11 ] 39.7 ± 10.7 [ 23 – 58 ] 11.4 ± 6.4 [ 1 – 26 ] 8.0 ± 4.1 [ 2 – 17 ] 0.39 0.012 0.034 Cognitive Complaint (Fact-Cog-PCA & Fact-Cog-PCI) 20.1 ± 4.4 57.2 ± 10.7 17.3 ± 6.1 53.4 ± 16.9 0.05 0.75 BC patients reported significantly more sleep complaints (p = 0.034) and more severe insomnia symptoms (p = 0.012) compared to HCs (Table 1 ). ----------------------------------------------------------- Insert Table 1 ----------------------------------------------------------- Comparison of nocturnal hypoxia between BC patients and HCs The nocturnal hypoxia scores are presented in Fig. 1 . The composite hypoxia score differed significantly between the two groups, indicating more severe hypoxia, as assessed with the composite score, in BC patients compared to HCs ( p = 0.028). Specifically, BC patients had lower minimal SpO 2 than HCs (BC: 84.8 ± 5.5; HC: 88.1 ± 4.2; p = 0.028). However, there were no significant differences between the groups for ODI (BC: 13.5 ± 10.7; HCs: 11.7 ± 11; p = 0.48) or TST90% (BC: 3.6 ± 6.6; HCs: 0.6 ± 0.8; p = 0.26). ----------------------------------------------------------- Insert Fig. 1 ----------------------------------------------------------- Between-group differences for cognitive outcomes No significant differences in scores were found across all cognitive domains assessed. However, a tendency towards a significant difference was observed for the episodic memory composite score ( p = 0.06) (Table 2 ). For more details on raw neuropsychological test scores, please refer to Table S1 in the Supplemental document. Table 2 Comparison of Cognitive scores between BC patients and HCs. HC (n = 21) BC (n = 35) p-value Global Cognitive Functioning MoCA (/30) 27.85 ± 1.35 26.86 ± 3.13 0.11 Cognitive composite z-scores Executive function 0.00 ± 0.69 -0.19 ± 0.71 0.38 Processing speed 0.00 ± 0.76 -0.46 ± 1.11 0.11 Working memory 0.00 ± 0.75 -0.22 ± 0.76 0.33 Episodic memory 0.00 ± 0.75 -0.81 ± 2.03 0.06 P -values in italics show the trends towards significance ----------------------------------------------------------- Insert Table 2 ----------------------------------------------------------- Relationship between nocturnal hypoxia and cognitive performance in the entire sample We performed multivariable models to determine whether nocturnal hypoxia was associated with cognitive performance in BC. The results are presented in Table 3 . No significant association were found between the composite hypoxia score and the composite scores of the different cognitive domains, nor when the predictor was the interaction between group and hypoxia ( ps > 0.05 ). To minimize the risk of missing any specific effects, we examined the relationships between hypoxia and individual cognitive test scores (See Supplemental Online Content 1). These exploratory analyses did not reveal any significant associations (ps > 0.05). Table 3 Multivariable linear models measuring the relationship between Nocturnal Hypoxia and Cognitive Performance in the entire sample Predictors Executive functioning Processing speed Working memory Episodic memory β p β p β p β p Depression 0.019 0.56 -0.009 0.85 0.009 0.81 0.15 0.07 Anxiety -0.018 0.08 0.008 0.57 -0.003 0.79 -0.04 0.16 Hypoxia 0.51 0.16 -0.87 0.08 -0.04 0.92 0.002 0.99 Group -0.21 0.33 -0.52 0.08 -0.22 0.35 -0.91 0.07 Group*hypoxia -0.47 0.18 0.84 0.10 0.04 0.91 -0.09 0.91 P -values in italics show the trends towards significance. ----------------------------------------------------------- Insert Table 3 ----------------------------------------------------------- Discussion To our knowledge, this is the first study to explore the relationship between nocturnal hypoxia and cognitive performance in BC. All participants underwent full-night ambulatory PSG and the same cognitive assessments. A significant difference for nocturnal hypoxia was observed between the two groups, with BC patients experiencing more frequent hypoxia than HCs. However, no significant associations were found with cognitive scores. One possible explanation for the differences between prior non-cancer studies reporting hypoxia-related cognitive impairment and our results relates to differences in the degree of nocturnal hypoxia. Actually, in our sample, nocturnal hypoxia is mild when compared to populations from SDB cohorts (25–32) which might reduce the relationship with cognition. For example, chronic hypoxia in SDB was found to directly cause neuronal injury in the hippocampus and frontal cortex, leading to deficits in attention, memory and executive function (54). In addition, cognitive impairment is common in BC and is primarily attributed to cancer treatments, inflammation and psychological factors (55, 56). These factors might overshadow nocturnal hypoxia’s effect on cognition in our sample. In line with previous research (e.g., (57,58)), our results revealed an increase in cognitive complaints, as measured by the “perceived cognitive abilities” subscale of the FACT-Cog, in BC patients compared to HCs. In this regard, BC patients reported a perceived decline in their cognitive abilities, whereas HCs did not perceive any significant reduction in their cognitive function. However, no significant differences were observed between the two groups in terms of objective cognitive scores, except for a tendency toward significance in episodic memory. Even-though this finding did not reach statistical significance, it suggests an area for additional research, as episodic memory has been identified as vulnerable in previous studies (12,14,59,60). Our patients were primarily treated with RT and/or ET, with none receiving chemotherapy. This may explain why their cognitive performance was not impaired as expected. Previous research indicates that ET and RT generally have less impact on cognition compared to chemotherapy. For example, a survey of 2296 BC patients aged 34 to 82 revealed that 60% experienced cognitive symptoms following treatment, with more pronounced cognitive symptoms in patients treated exclusively with chemotherapy than in those who received only ET (61). While rates of cognitive dysfunction in BC patients following ET vary between 32 and 64% (62), the findings in the literature remain inconsistent (63). In their literature review, Haggstrom and colleagues (63) presented 72 studies on CRCI in BC patients treated with ET: some studies indicated an impact of ET on cognition, others found no effect, concluding that underdiagnosis of CRCI related to ET is common and should be better addressed. In the current study, patients treated with both ET and RT, or with RT alone, demonstrated comparable cognitive performance (see Supplemental Table 1). In the context of SDB, only one study has addressed its prevalence among BC patients. This study showed an 88% prevalence of SDB in this population following chemotherapy, RT and/or ET (21). However, the prevalence of SDB has been studied in other types of cancer, and particularly following RT. In a systematic review, Tawfik and colleagues (64) showed a positive association between the occurrence of SDB and RT in 103 of 181 head and neck cancer patients (OR 1.16, 95% CI [0.52–2.56]; P = 0.718) with an overall prevalence of 63% (95% CI [0.36–0.85]; P = 0.343) and thus recommending the screening of all cancer patients treated with RT for early signs of SDB. In the current study, higher hypoxia in our sample of patients may be the result of the effects of RT. However, this issue remains understudied in BC patients and warrants further investigation. Additionally, it is worth mentioning that ET is a treatment that suppresses the production of estrogen and progesterone (65). The absence of these hormones due to ET may lead to relaxation of the pharyngeal muscles, potentially resulting in greater airway obstruction and an increased risk of hypoxia. In the current study, no significant differences in nocturnal hypoxia were noted between patients treated with both ET and RT and patients treated with RT alone (See Supplemental Table S2). Therefore, ET may not be the primary factor influencing hypoxia in our sample. Finally, menopause is another factor that may explain the presence of hypoxia in our sample. Menopause leads to a reduction in estrogen and progesterone levels (66). These hormones play a role in maintaining airway function by preserving the muscle tone of the throat (67). Therefore, a reduction in these hormones could increase the likelihood of developing SDB by decreasing muscle tone, thus leading to more breathing difficulties (68). While we cannot draw definitive conclusions at this stage, our results suggest that both treatment (probably RT, but not ET) and menopause may contribute to the presence of SDB and, consequently, nocturnal hypoxia in our sample. Higher presence of SDB is our patient sample is consistent with larger sleep complaints in this group. Indeed, BC patients reported more sleep disturbances and more severe insomnia symptoms compared to HCs. This finding is consistent with previous studies showing that sleep-related complaints are particularly prevalent in BC patients (69–72). This study has several limitations. First, the cross-sectional design limits the assessment of causal relationships between nocturnal hypoxia and cognition in BC. Additionally, the small effect size may have reduced statistical power. Yet, the tendencies toward significance are particularly noteworthy, as they align with previous findings and highlight the potential impact of BC on specific cognitive functions. Furthermore, the cognitive tests used in this study may not have been sensitive enough to detect subtle cognitive impairments that BC patients report in daily life. These tests were conducted in laboratory settings, which do not capture the daily life difficulties patients face. Future research with a longitudinal design is needed to clarify these findings. Studies with pre-treatment baselines and multiple follow-ups might help determine the evolution of this relationship in BC patients. Also, future studies must include a larger sample size in order to increase statistical power. Objective sleep assessment methods such as PSG and more sensitive cognitive assessments are needed to clarify these findings. Detailed cognitive testing to explore whether nocturnal hypoxia impacts cognition directly or through indirect pathways. This might allow us to conclude whether the lack of significant association demonstrated in our sample reflects treatment effects or a true absence of association. In conclusion, nocturnal hypoxia is not associated with cognitive performance in our sample. Although hypoxia is more frequent during the night in BC patients compared to HCs, it may not be the primary factor contributing to cognitive difficulties in this population, and other sleep disturbances may play a role in explaining cognitive performance in this population. Future studies are needed in this field. Materials and Methods Participants Data were gathered from the PROSOM-K project (37). All participants gave their written informed consent, and the study was approved by an ethics committee (CPP Ile de France III), with approval number ID-RCB: 2017-A02778-45. Patients were recruited at the Comprehensive Regional Cancer Centre, François Baclesse (Caen, Normandy, France). The study included two groups: 35 BC patients and 21 HCs. Patient inclusion criteria were: (i) less than 70 years old, (ii) no metastatic BC, (iii) already undergone surgical or RT treatment, (iv) menopausal status since at least one year ago at the time of inclusion, (v) no personality disorder and progressive psychiatric disorder, (vi) no neurological sequelae, (vii) no drug use or use of alcohol, (viii) be a native French speaker, (ix) have at least a primary school level of education. Inclusion criteria of HCs were the same as for patients, including no history of cancer and no global cognitive impairment according to the Montreal Cognitive Assessment (38). HC were matched in age and education with BC patients (Table 1 ). Measures Anxiety and depression assessments Depression was assessed with the Beck Depression Inventory (BDI) (39). Anxiety was measured with the State-Trait Anxiety Inventory (STAI-Y) (40). BDI evaluates depression using a 21-item scale that provides information about the severity and nature of depression in the participants. The items range from 0 = the absence of symptoms to 3 = an intense level. The sum of the score will define the presence and severity of depression. A score of 1–10 = absence of depression, 11–16 = mild mood disturbance, 17–20 = borderline clinical depression, 21–30 = moderate depression, 31–40 = severe depression, and finally, a score over 40 = extreme depression. In regards to STAI-Y, the first 20 items assess state anxiety (STAI-A), or how the participant feels right now; the second 20 items assess trait anxiety (STAI-B), or how the participant generally feels. Higher scores indicate higher depression and anxiety symptoms, respectively. Self-reported sleep quality assessments The Insomnia Severity Index (ISI) (41) is a self-report questionnaire assessing the nature, severity, and impact of insomnia. It evaluates the following dimensions: severity of sleep onset, sleep maintenance, early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by sleep difficulties. A score ≥ 7 is considered to indicate the presence of insomnia. The Pittsburgh Sleep Quality Index (PSQI) (42) is a self-report questionnaire that is used to assess efficiency and quality of sleep over a 1-month time interval. It measures the following components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. A score > 5 is considered to indicate a significant sleep disturbance. Neuropsychological assessments Subjective cognitive complaints were assessed using the Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) in its French version (43). Episodic memory was assessed with the RL/RI-16 test (44), a French adaptation of the Grober and Buschke ’s procedure. We calculated the sum of the three immediate free recall scores, the sum of the three immediate total (i.e., free and cued) recall scores, and we used the delayed free recall and the delayed total recall scores. Working memory was assessed with the Digit Span forward and backward test (45). Episodic buffer was assessed with a binding task, the multimodal integration task (46): participants had to mentally associate four colored letters and the location of the cross of the same color randomly distributed over a grid. Then a grid appeared with one black letter and the participants indicated if it was correctly located. The score corresponded to the number of correct trials. The assessment of executive functions focused on three domains, each evaluated through specific cognitive tests. Planning was assessed using the score of accuracy in part 1 of the Zoo Map Test (47). Flexibility was evaluated using the Trail Making Test (TMT; (48)), by the following score [TMTB time – TMTA time]/TMTA time. Inhibition was measured with the Stroop test (49), [Interference time – Color time]/ Word time. Processing speed corresponded to the average mean time taken to name the colors of the Stroop test and to perform the TMT Part A. To minimize the issue of multiple statistical testing, we computed composite scores for each cognitive domain. Performance on various cognitive tests were z-transformed and averaged. Before averaging, Z-scores derived from reaction times, percentages/number of errors were reversed so that increasing values always indicated better performance. Accordingly, we categorized four cognitive composite scores: Executive Function, Processing Speed, Working Memory and Episodic Memory (See Supplement). Hypoxia characterization All participants underwent a full night recording of sleep using ambulatory PSG at home with monitoring of EEG, EOG, chin, diaphragm and EMG, nasal pressure, oro-nasal thermistor signals, sound (snoring), thoracic and abdominal plethysmography and pulse oximetry routinely used in PSG to measure minimal oxygen saturation (SpO 2 ). All sensors were connected to the Compumedics Siesta sleep system and placed by an EEG technician. Sleep scoring was conducted according to American Academy of Sleep Medicine criteria (AASM) (50). Three variables were extracted to reflect hypoxia as previously proposed (51,52). As defined by Berry and colleagues (53) following The AASM Manual for the Scoring of Sleep and Associated Events: Oxygen Desaturation Index ≥ 3% (ODI) is defined as the number of times per hour of sleep that blood oxygen levels drop by 3% or more from baseline levels. Total Sleep Time with oxygen saturation ≤ 90% (TST90%) represents the cumulative amount of time during which the blood oxygen saturation levels remain at or below 90% throughout the sleep period. Minimal Oxygen Saturation (SpO 2 %) reflects the lowest recorded oxygen saturation level during the sleep period. A lower SpO 2 is a marker of severe oxygen desaturation episodes. We also computed a composite score for nocturnal hypoxia. The hypoxia composite scores correspond to the mean of z scores of SpO2%, ODI and TST90% (51). Z-scores derived from ODI and TST90% were reversed so that increasing values always indicated better respiratory efficiency. Statistical analysis Demographical and clinical characteristics were described using mean, standard deviation and range for quantitative variables and using frequencies and percentage for qualitative variables. The Shapiro-Wilk test was used to assess the normality of the data. Since the normality test was rejected, we applied the non-parametric Wilcoxon Mann-Whitney test to compare demographic, sleep, cognitive, and quality of life characteristics between the groups. Finally, we conducted multivariable models to determine whether hypoxia was associated with cognitive functioning in BC. These models were, adjusted on age, anxiety (STAI-B), depression (BDI), and the group effect, as these factors are known to influence cognitive functioning and performed on the whole sample. Analyses were conducted using R software, version 4.3.0 with statistical significance set at p < .05. Declarations Competing interests: The authors declare no competing interests. Ethics approval : The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The studies involving human participants were reviewed and approved by CPP Ile de France III (n◦ ID-RCB: 2017- A02778-45). The patients/participants provided their written informed consent to participate in this study. Consent to participate: Written informed consent was obtained from all individual participants included in the study. Funding: This work was supported by the ARC foundation—for cancer research (2017–2020), the French sleep society (SFRMS), the Région Normandie (Réseaux d’Intérêts Normands, RIN), the Cancéropôle Nord-Ouest, and the Ligue Contre le Cancer - Normandie. Clara Elia was funded by a PhD grant from the University of Caen Normandy, and from the Ligue Nationale Contre le Cancer. Author Contribution Conceptualization: Bénédicte Giffard, Francis Eustache, Florence Joly, Joy Perrier; Writing – original draft preparation: Clara Elia; Writing – review and editing: Clara Elia, Bénédicte Giffard, Joy Perrier; Investigation: Mylène Duivon, Stéphane Rehel, François Gernier, Marie Fernette, Carine Segura-Djezzar, Julien Geffrelot, George Emile, Djelila Allouache, Fausto Viader, Christelle Lévy ; Methodological support: Franck Doidy, Patrice Clochon; Data analyses: Clara Elia, Joy Perrier, Stéphane Rehel, François Christy; Project administration: Jean-Michel Grellard; Funding acquisition: Bénédicte Giffard, Joy Perrier, Francis Eustache ; Supervision: Bénédicte Giffard, Joy Perrier ; All authors have critically revised the final version of the manuscript and have approved its current version. Acknowledgement Authors would like to thank the clinical research department and the medical oncology department of the Centre François Baclesse for their help in patient recruitment, the Interdisciplinary Center for Virtual Reality (CIREVE) in Caen (Normandy, France) for their technical support, and all the participants for their active contribution to these results. The Northwest Data Center (CTD-CNO) is acknowledged for managing the data. Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. References European Cancer and Cognition Consortium (ECCC), Sleurs, C., Amidi, A., Wu, L. M.,Kiesl, D., Zimmer, P., Lange, M., Rogiers, A., Giffard, B., Binarelli, G., Borghgraef,C., Deprez, S., Duivon, M., De Ruiter, M., Schagen, S., Ahmed-Lecheheb, D., Castel,H., Buskbjerg, C. R., Dos Santos, M., Joly, F., … Perrier, J. (2022). 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Additional Declarations No competing interests reported. Supplementary Files EliaetalSupplementaloriginalarticle.docx Cite Share Download PDF Status: Published Journal Publication published 27 Nov, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Accepted 29 Oct, 2025 Reviews received at journal 28 Oct, 2025 Reviewers agreed at journal 28 Oct, 2025 Reviewers invited by journal 27 Oct, 2025 Submission checks completed at journal 24 Oct, 2025 First submitted to journal 21 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":50089,"visible":true,"origin":"","legend":"\u003cp\u003eComparisons of nocturnal hypoxia variables between BC patients and HCs. A. The hypoxia composite score differed significantly between the two groups, indicating more frequent hypoxia in BC patients compared to HCs. B. No significant difference was found for the Oxygen Desaturation Index ≥3% (ODI ≥3%). C. No significant difference was observed for Total Sleep Time with oxygen saturation ≤90% (TST90%). D. A significant between-group difference was found for Minimal Oxygen Saturation (SpO\u003csub\u003e2\u003c/sub\u003e).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6016528/v1/e81859de42633158604d7dfd.png"},{"id":97178902,"identity":"85ad51a4-ae34-4fc2-811f-1fdfe7a70fdc","added_by":"auto","created_at":"2025-12-01 16:14:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1111861,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6016528/v1/8faeaf37-8f6a-4fd5-9a40-05530b5f52f6.pdf"},{"id":94662659,"identity":"474ce50a-7be4-4aa0-9492-c782d3192f10","added_by":"auto","created_at":"2025-10-29 12:08:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":21748,"visible":true,"origin":"","legend":"","description":"","filename":"EliaetalSupplementaloriginalarticle.docx","url":"https://assets-eu.researchsquare.com/files/rs-6016528/v1/98d3064d9d250674cd052dac.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Links between nocturnal hypoxia and cognitive function in breast cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCognitive deficits in cancer, often referred to as \u0026ldquo;cancer-related cognitive impairments\u0026rdquo; (CRCI), are commonly reported by breast cancer (BC) patients. CRCI are mainly subtle in nature and concern difficulties in memory, attention, executive functions, and processing speed (1\u0026ndash;3). Despite their subtle nature, these impairments can persist (4) and negatively impact the quality of life of BC patients, hindering their ability to return to work and resume daily activities (5,6).\u003c/p\u003e\u003cp\u003eCognitive complaints are frequently reported by BC patients following chemotherapy (7,8), and some studies also suggest an exacerbation of cognitive complaints among BC women undergoing endocrine therapy (ET) (9,10). Besides cancer treatments, other factors such as age, psycho-affective and medical comorbidities, and sleep disorders can also contribute to the occurrence and persistence of cognitive decline in BC (11\u0026ndash;16). Notably, self-reported sleep difficulties were found to be strongly associated with CRCI (12,17), and many BC patients express sleep difficulties (13,18,19).\u003c/p\u003e\u003cp\u003eOne of the most commonly reported symptoms of sleep disturbances in BC patients is sleep-disordered breathing (SDB) (20). Specifically, SDB is a syndrome characterized by upper airway dysfunction during sleep, marked by snoring, heightened respiratory effort caused by increased resistance in the upper airway, and the tendency of the pharynx to collapse (21,22). The primary consequences of SDB are nocturnal hypoxia and sleep fragmentation (23). Interest in exploring the prevalence of SDB in BC patients has grown recently, marked by the initiation of a first study in 2021, which used polysomnography (PSG) in BC patients treated with chemotherapy, radiotherapy (RT) and/or ET (24). This study found an 88% prevalence of SDB in BC patients. It is important to note, however, that the study did not compare its results to a control group. Individuals without cancer experiencing SDB often demonstrate cognitive difficulties (25\u0026ndash;27), particularly affecting memory, executive functions, and attention (28). Additionally, numerous studies have confirmed an association between SDB and cognitive decline in older adults (25,29\u0026ndash;32).\u003c/p\u003e\u003cp\u003eHypoxia refers to a condition characterized by a reduced intake of oxygen or an impaired ability of oxygen use (33). Since the brain depends on an important oxygen supply to assure neuronal connectivity and synaptic activity (34), oxygen deprivation can lead to cognitive dysfunction (35). A recent literature review concluded that hypoxia is the primary contributor to cognitive dysfunction in elderly patients (29). Similarly, a study by Yaffe and colleagues (31) found that nocturnal hypoxia was more commonly associated with cognitive decline than other sleep-related disturbances. While sleep fragmentation and nocturnal hypoxia often co-occur in SDB, sleep fragmentation primarily impacts cognition through secondary mechanisms such as increased daytime sleepiness and reduced vigilance (36). In the 2011 study by Yaffe and colleagues (31), no association was found between sleep fragmentation and cognitive impairment, further supporting the dominant role of nocturnal hypoxia in cognitive decline.\u003c/p\u003e\u003cp\u003eDespite the presence of cognitive impairment in BC, and despite evidence linking hypoxia to cognitive impairment in the general population, this link has yet to be explored in BC. This highlights a significant gap in the available data, hindering the effective management of hypoxia and, as a result, limiting the potential to improve patients\u0026rsquo; quality of life. The current study aims to characterize the presence of nocturnal hypoxia and its association with cognitive functioning in BC patients compared to HCs. By investigating the relationship between hypoxia and CRCI, we hypothesize that nocturnal hypoxia will be linked to cognitive impairment in BC patients.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eClinical and demographic characteristics of the sample\u003c/h2\u003e\u003cp\u003eThe demographic and clinical characteristics of the participants are provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No significant differences were observed between BC patients and HCs in terms of demographic characteristics or depression (\u003cem\u003ep\u003c/em\u003es\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, a significant difference was observed on the state anxiety as measured by STAI-A (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.02).\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD [range]) and clinical (\u003cem\u003en\u003c/em\u003e (%)) characteristics, and self-reported outcomes of HCs and BC patients. P values\u0026thinsp;\u0026le;\u0026thinsp;0.05 are in bold\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHCs (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBC (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR55 CR56 CR57 CR58 CR59 CR60 CR61 CR62 CR63 CR64 CR65 CR66 CR67 CR68\" citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR52 CR53 CR54 CR55 CR56 CR57 CR58 CR59 CR60 CR61 CR62 CR63 CR64 CR65 CR66 CR67 CR68\" citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer stage, n (%):\u003c/p\u003e\u003cp\u003e0, I, IIA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e17\u003c/em\u003e (53), \u003cem\u003e13\u003c/em\u003e (38), \u003cem\u003e5\u003c/em\u003e (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery, n (%):\u003c/p\u003e\u003cp\u003eTumorectomy, Mastectomy, Both\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e30\u003c/em\u003e (86), \u003cem\u003e4\u003c/em\u003e (11), \u003cem\u003e1\u003c/em\u003e (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine therapy (ET), n (%):\u003c/p\u003e\u003cp\u003eTreated with, not treated with ET\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e18\u003c/em\u003e (51), \u003cem\u003e17\u003c/em\u003e (49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime since diagnosis (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSelf-reported measures\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDepression (BDI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\u003cp\u003e[0\u0026ndash;13]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003cp\u003e[0\u0026ndash;14]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState Anxiety (STAI-A)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44.43\u0026thinsp;\u0026plusmn;\u0026thinsp;14.83\u003c/p\u003e\u003cp\u003e[24\u0026ndash;78]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.65\u0026thinsp;\u0026plusmn;\u0026thinsp;11.75 [\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53 CR54 CR55 CR56 CR57 CR58 CR59 CR60 CR61 CR62 CR63 CR64 CR65 CR66 CR67 CR68 CR69 CR70 CR71\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrait Anxiety (STAI-B)\u003c/p\u003e\u003cp\u003eInsomnia Severity Index (ISI)\u003c/p\u003e\u003cp\u003eSleep quality (PSQI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53 CR54 CR55 CR56 CR57 CR58 CR59 CR60 CR61 CR62 CR63 CR64 CR65 CR66 CR67\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e\u003cp\u003e[0\u0026ndash;16]\u003c/p\u003e\u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53 CR54 CR55 CR56 CR57\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003cp\u003e[\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCognitive Complaint (Fact-Cog-PCA \u0026amp;\u003c/p\u003e\u003cp\u003eFact-Cog-PCI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003cp\u003e57.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003cp\u003e53.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBC patients reported significantly more sleep complaints (p\u0026thinsp;=\u0026thinsp;0.034) and more severe insomnia symptoms (p\u0026thinsp;=\u0026thinsp;0.012) compared to HCs (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\u003cp\u003eInsert Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eComparison of nocturnal hypoxia between BC patients and HCs\u003c/h3\u003e\n\u003cp\u003eThe nocturnal hypoxia scores are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The composite hypoxia score differed significantly between the two groups, indicating more severe hypoxia, as assessed with the composite score, in BC patients compared to HCs (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028). Specifically, BC patients had lower minimal SpO\u003csub\u003e2\u003c/sub\u003e than HCs (BC: 84.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5; HC: 88.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028). However, there were no significant differences between the groups for ODI (BC: 13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7; HCs: 11.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.48) or TST90% (BC: 3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6; HCs: 0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.26).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\u003cp\u003eInsert Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\n\u003ch3\u003eBetween-group differences for cognitive outcomes\u003c/h3\u003e\n\u003cp\u003eNo significant differences in scores were found across all cognitive domains assessed. However, a tendency towards a significant difference was observed for the episodic memory composite score (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.06) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For more details on raw neuropsychological test scores, please refer to Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e in the Supplemental document.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Cognitive scores between BC patients and HCs.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHC (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBC (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGlobal Cognitive Functioning\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMoCA (/30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e27.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e26.86\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCognitive composite z-scores\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExecutive function\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProcessing speed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-0.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWorking memory\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-0.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpisodic memory\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0.06\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eP\u003c/em\u003e-values in italics show the trends towards significance\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\u003cp\u003eInsert Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\n\u003ch3\u003eRelationship between nocturnal hypoxia and cognitive performance in the entire sample\u003c/h3\u003e\n\u003cp\u003eWe performed multivariable models to determine whether nocturnal hypoxia was associated with cognitive performance in BC. The results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. No significant association were found between the composite hypoxia score and the composite scores of the different cognitive domains, nor when the predictor was the interaction between group and hypoxia (\u003cem\u003eps\u0026thinsp;\u0026gt;\u0026thinsp;0.05\u003c/em\u003e). To minimize the risk of missing any specific effects, we examined the relationships between hypoxia and individual cognitive test scores (See Supplemental Online Content 1). These exploratory analyses did not reveal any significant associations (ps\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariable linear models measuring the relationship between Nocturnal Hypoxia and Cognitive Performance in the entire sample\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePredictors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExecutive functioning\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eProcessing speed\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eWorking memory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003eEpisodic memory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDepression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e\u003cem\u003e0.07\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0.08\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypoxia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e0.08\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e0.08\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e\u003cem\u003e0.07\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup*hypoxia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003cem\u003eP\u003c/em\u003e-values in italics show the trends towards significance.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e\u003cp\u003eInsert Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e\u003cp\u003e-----------------------------------------------------------\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study to explore the relationship between nocturnal hypoxia and cognitive performance in BC. All participants underwent full-night ambulatory PSG and the same cognitive assessments. A significant difference for nocturnal hypoxia was observed between the two groups, with BC patients experiencing more frequent hypoxia than HCs. However, no significant associations were found with cognitive scores.\u003c/p\u003e\u003cp\u003eOne possible explanation for the differences between prior non-cancer studies reporting hypoxia-related cognitive impairment and our results relates to differences in the degree of nocturnal hypoxia. Actually, in our sample, nocturnal hypoxia is mild when compared to populations from SDB cohorts (25\u0026ndash;32) which might reduce the relationship with cognition. For example, chronic hypoxia in SDB was found to directly cause neuronal injury in the hippocampus and frontal cortex, leading to deficits in attention, memory and executive function (54). In addition, cognitive impairment is common in BC and is primarily attributed to cancer treatments, inflammation and psychological factors (55, 56). These factors might overshadow nocturnal hypoxia\u0026rsquo;s effect on cognition in our sample.\u003c/p\u003e\u003cp\u003eIn line with previous research (e.g., (57,58)), our results revealed an increase in cognitive complaints, as measured by the \u0026ldquo;perceived cognitive abilities\u0026rdquo; subscale of the FACT-Cog, in BC patients compared to HCs. In this regard, BC patients reported a perceived decline in their cognitive abilities, whereas HCs did not perceive any significant reduction in their cognitive function. However, no significant differences were observed between the two groups in terms of objective cognitive scores, except for a tendency toward significance in episodic memory. Even-though this finding did not reach statistical significance, it suggests an area for additional research, as episodic memory has been identified as vulnerable in previous studies (12,14,59,60). Our patients were primarily treated with RT and/or ET, with none receiving chemotherapy. This may explain why their cognitive performance was not impaired as expected. Previous research indicates that ET and RT generally have less impact on cognition compared to chemotherapy. For example, a survey of 2296 BC patients aged 34 to 82 revealed that 60% experienced cognitive symptoms following treatment, with more pronounced cognitive symptoms in patients treated exclusively with chemotherapy than in those who received only ET (61). While rates of cognitive dysfunction in BC patients following ET vary between 32 and 64% (62), the findings in the literature remain inconsistent (63). In their literature review, Haggstrom and colleagues (63) presented 72 studies on CRCI in BC patients treated with ET: some studies indicated an impact of ET on cognition, others found no effect, concluding that underdiagnosis of CRCI related to ET is common and should be better addressed. In the current study, patients treated with both ET and RT, or with RT alone, demonstrated comparable cognitive performance (see Supplemental Table\u0026nbsp;1).\u003c/p\u003e\u003cp\u003eIn the context of SDB, only one study has addressed its prevalence among BC patients. This study showed an 88% prevalence of SDB in this population following chemotherapy, RT and/or ET (21). However, the prevalence of SDB has been studied in other types of cancer, and particularly following RT. In a systematic review, Tawfik and colleagues (64) showed a positive association between the occurrence of SDB and RT in 103 of 181 head and neck cancer patients (OR 1.16, 95% CI [0.52\u0026ndash;2.56]; P\u0026thinsp;=\u0026thinsp;0.718) with an overall prevalence of 63% (95% CI [0.36\u0026ndash;0.85]; P\u0026thinsp;=\u0026thinsp;0.343) and thus recommending the screening of all cancer patients treated with RT for early signs of SDB. In the current study, higher hypoxia in our sample of patients may be the result of the effects of RT. However, this issue remains understudied in BC patients and warrants further investigation. Additionally, it is worth mentioning that ET is a treatment that suppresses the production of estrogen and progesterone (65). The absence of these hormones due to ET may lead to relaxation of the pharyngeal muscles, potentially resulting in greater airway obstruction and an increased risk of hypoxia. In the current study, no significant differences in nocturnal hypoxia were noted between patients treated with both ET and RT and patients treated with RT alone (See Supplemental Table S2). Therefore, ET may not be the primary factor influencing hypoxia in our sample. Finally, menopause is another factor that may explain the presence of hypoxia in our sample. Menopause leads to a reduction in estrogen and progesterone levels (66). These hormones play a role in maintaining airway function by preserving the muscle tone of the throat (67). Therefore, a reduction in these hormones could increase the likelihood of developing SDB by decreasing muscle tone, thus leading to more breathing difficulties (68). While we cannot draw definitive conclusions at this stage, our results suggest that both treatment (probably RT, but not ET) and menopause may contribute to the presence of SDB and, consequently, nocturnal hypoxia in our sample. Higher presence of SDB is our patient sample is consistent with larger sleep complaints in this group. Indeed, BC patients reported more sleep disturbances and more severe insomnia symptoms compared to HCs. This finding is consistent with previous studies showing that sleep-related complaints are particularly prevalent in BC patients (69\u0026ndash;72).\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, the cross-sectional design limits the assessment of causal relationships between nocturnal hypoxia and cognition in BC. Additionally, the small effect size may have reduced statistical power. Yet, the tendencies toward significance are particularly noteworthy, as they align with previous findings and highlight the potential impact of BC on specific cognitive functions. Furthermore, the cognitive tests used in this study may not have been sensitive enough to detect subtle cognitive impairments that BC patients report in daily life. These tests were conducted in laboratory settings, which do not capture the daily life difficulties patients face. Future research with a longitudinal design is needed to clarify these findings. Studies with pre-treatment baselines and multiple follow-ups might help determine the evolution of this relationship in BC patients. Also, future studies must include a larger sample size in order to increase statistical power. Objective sleep assessment methods such as PSG and more sensitive cognitive assessments are needed to clarify these findings. Detailed cognitive testing to explore whether nocturnal hypoxia impacts cognition directly or through indirect pathways. This might allow us to conclude whether the lack of significant association demonstrated in our sample reflects treatment effects or a true absence of association.\u003c/p\u003e\u003cp\u003eIn conclusion, nocturnal hypoxia is not associated with cognitive performance in our sample. Although hypoxia is more frequent during the night in BC patients compared to HCs, it may not be the primary factor contributing to cognitive difficulties in this population, and other sleep disturbances may play a role in explaining cognitive performance in this population. Future studies are needed in this field.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eData were gathered from the PROSOM-K project (37). All participants gave their written informed consent, and the study was approved by an ethics committee (CPP Ile de France III), with approval number ID-RCB: 2017-A02778-45. Patients were recruited at the Comprehensive Regional Cancer Centre, Fran\u0026ccedil;ois Baclesse (Caen, Normandy, France). The study included two groups: 35 BC patients and 21 HCs.\u003c/p\u003e\u003cp\u003ePatient inclusion criteria were: (i) less than 70 years old, (ii) no metastatic BC, (iii) already undergone surgical or RT treatment, (iv) menopausal status since at least one year ago at the time of inclusion, (v) no personality disorder and progressive psychiatric disorder, (vi) no neurological sequelae, (vii) no drug use or use of alcohol, (viii) be a native French speaker, (ix) have at least a primary school level of education. Inclusion criteria of HCs were the same as for patients, including no history of cancer and no global cognitive impairment according to the Montreal Cognitive Assessment (38). HC were matched in age and education with BC patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMeasures\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eAnxiety and depression assessments\u003c/h2\u003e\u003cp\u003eDepression was assessed with the Beck Depression Inventory (BDI) (39). Anxiety was measured with the State-Trait Anxiety Inventory (STAI-Y) (40). BDI evaluates depression using a 21-item scale that provides information about the severity and nature of depression in the participants. The items range from 0\u0026thinsp;=\u0026thinsp;the absence of symptoms to 3\u0026thinsp;=\u0026thinsp;an intense level. The sum of the score will define the presence and severity of depression. A score of 1\u0026ndash;10\u0026thinsp;=\u0026thinsp;absence of depression, 11\u0026ndash;16\u0026thinsp;=\u0026thinsp;mild mood disturbance, 17\u0026ndash;20\u0026thinsp;=\u0026thinsp;borderline clinical depression, 21\u0026ndash;30\u0026thinsp;=\u0026thinsp;moderate depression, 31\u0026ndash;40\u0026thinsp;=\u0026thinsp;severe depression, and finally, a score over 40\u0026thinsp;=\u0026thinsp;extreme depression. In regards to STAI-Y, the first 20 items assess state anxiety (STAI-A), or how the participant feels right now; the second 20 items assess trait anxiety (STAI-B), or how the participant generally feels. Higher scores indicate higher depression and anxiety symptoms, respectively.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eSelf-reported sleep quality assessments\u003c/h2\u003e\u003cp\u003eThe Insomnia Severity Index (ISI) (41) is a self-report questionnaire assessing the nature, severity, and impact of insomnia. It evaluates the following dimensions: severity of sleep onset, sleep maintenance, early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by sleep difficulties. A score\u0026thinsp;\u0026ge;\u0026thinsp;7 is considered to indicate the presence of insomnia.\u003c/p\u003e\u003cp\u003eThe Pittsburgh Sleep Quality Index (PSQI) (42) is a self-report questionnaire that is used to assess efficiency and quality of sleep over a 1-month time interval. It measures the following components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. A score\u0026thinsp;\u0026gt;\u0026thinsp;5 is considered to indicate a significant sleep disturbance.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eNeuropsychological assessments\u003c/h2\u003e\u003cp\u003eSubjective cognitive complaints were assessed using the Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) in its French version (43).\u003c/p\u003e\u003cp\u003eEpisodic memory was assessed with the RL/RI-16 test (44), a French adaptation of \u003cem\u003ethe Grober and Buschke\u003c/em\u003e\u0026rsquo;s procedure. We calculated the sum of the three immediate free recall scores, the sum of the three immediate total (i.e., free and cued) recall scores, and we used the delayed free recall and the delayed total recall scores.\u003c/p\u003e\u003cp\u003eWorking memory was assessed with the Digit Span forward and backward test (45). Episodic buffer was assessed with a binding task, the multimodal integration task (46): participants had to mentally associate four colored letters and the location of the cross of the same color randomly distributed over a grid. Then a grid appeared with one black letter and the participants indicated if it was correctly located. The score corresponded to the number of correct trials.\u003c/p\u003e\u003cp\u003eThe assessment of executive functions focused on three domains, each evaluated through specific cognitive tests. Planning was assessed using the score of accuracy in part 1 of the Zoo Map Test (47). Flexibility was evaluated using the Trail Making Test (TMT; (48)), by the following score [TMTB time \u0026ndash; TMTA time]/TMTA time. Inhibition was measured with the Stroop test (49), [Interference time \u0026ndash; Color time]/ Word time.\u003c/p\u003e\u003cp\u003eProcessing speed corresponded to the average mean time taken to name the colors of the Stroop test and to perform the TMT Part A.\u003c/p\u003e\u003cp\u003eTo minimize the issue of multiple statistical testing, we computed composite scores for each cognitive domain. Performance on various cognitive tests were z-transformed and averaged. Before averaging, Z-scores derived from reaction times, percentages/number of errors were reversed so that increasing values always indicated better performance. Accordingly, we categorized four cognitive composite scores: Executive Function, Processing Speed, Working Memory and Episodic Memory (See Supplement).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eHypoxia characterization\u003c/h2\u003e\u003cp\u003eAll participants underwent a full night recording of sleep using ambulatory PSG at home with monitoring of EEG, EOG, chin, diaphragm and EMG, nasal pressure, oro-nasal thermistor signals, sound (snoring), thoracic and abdominal plethysmography and pulse oximetry routinely used in PSG to measure minimal oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e). All sensors were connected to the Compumedics Siesta sleep system and placed by an EEG technician. Sleep scoring was conducted according to American Academy of Sleep Medicine criteria (AASM) (50).\u003c/p\u003e\u003cp\u003eThree variables were extracted to reflect hypoxia as previously proposed (51,52). As defined by Berry and colleagues (53) following The AASM Manual for the Scoring of Sleep and Associated Events:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eOxygen Desaturation Index\u0026thinsp;\u0026ge;\u0026thinsp;3% (ODI) is defined as the number of times per hour of sleep that blood oxygen levels drop by 3% or more from baseline levels.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eTotal Sleep Time with oxygen saturation\u0026thinsp;\u0026le;\u0026thinsp;90% (TST90%) represents the cumulative amount of time during which the blood oxygen saturation levels remain at or below 90% throughout the sleep period.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinimal Oxygen Saturation (SpO\u003csub\u003e2\u003c/sub\u003e%) reflects the lowest recorded oxygen saturation level during the sleep period. A lower SpO\u003csub\u003e2\u003c/sub\u003e is a marker of severe oxygen desaturation episodes.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eWe also computed a composite score for nocturnal hypoxia. The hypoxia composite scores correspond to the mean of z scores of SpO2%, ODI and TST90% (51). Z-scores derived from ODI and TST90% were reversed so that increasing values always indicated better respiratory efficiency.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eDemographical and clinical characteristics were described using mean, standard deviation and range for quantitative variables and using frequencies and percentage for qualitative variables. The Shapiro-Wilk test was used to assess the normality of the data. Since the normality test was rejected, we applied the non-parametric Wilcoxon Mann-Whitney test to compare demographic, sleep, cognitive, and quality of life characteristics between the groups. Finally, we conducted multivariable models to determine whether hypoxia was associated with cognitive functioning in BC. These models were, adjusted on age, anxiety (STAI-B), depression (BDI), and the group effect, as these factors are known to influence cognitive functioning and performed on the whole sample. Analyses were conducted using R software, version 4.3.0 with statistical significance set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting interests:\u003c/h2\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003e\u003cb\u003eEthics approval\u003c/b\u003e:\u003c/h2\u003e\u003cp\u003e The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The studies involving human participants were reviewed and approved by CPP Ile de France III (n◦ ID-RCB: 2017- A02778-45). The patients/participants provided their written informed consent to participate in this study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003cp\u003e Written informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis work was supported by the ARC foundation\u0026mdash;for cancer research (2017\u0026ndash;2020), the French sleep society (SFRMS), the R\u0026eacute;gion Normandie (R\u0026eacute;seaux d\u0026rsquo;Int\u0026eacute;r\u0026ecirc;ts Normands, RIN), the Canc\u0026eacute;rop\u0026ocirc;le Nord-Ouest, and the Ligue Contre le Cancer - Normandie. Clara Elia was funded by a PhD grant from the University of Caen Normandy, and from the Ligue Nationale Contre le Cancer.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: B\u0026eacute;n\u0026eacute;dicte Giffard, Francis Eustache, Florence Joly, Joy Perrier; Writing \u0026ndash; original draft preparation: Clara Elia; Writing \u0026ndash; review and editing: Clara Elia, B\u0026eacute;n\u0026eacute;dicte Giffard, Joy Perrier; Investigation: Myl\u0026egrave;ne Duivon, St\u0026eacute;phane Rehel, Fran\u0026ccedil;ois Gernier, Marie Fernette, Carine Segura-Djezzar, Julien Geffrelot, George Emile, Djelila Allouache, Fausto Viader, Christelle L\u0026eacute;vy\u0026nbsp;; Methodological support: Franck Doidy, Patrice Clochon; Data analyses: Clara Elia, Joy Perrier, St\u0026eacute;phane Rehel, Fran\u0026ccedil;ois Christy; Project administration: Jean-Michel Grellard; Funding acquisition: B\u0026eacute;n\u0026eacute;dicte Giffard, Joy Perrier, Francis Eustache\u0026nbsp;; Supervision: B\u0026eacute;n\u0026eacute;dicte Giffard, Joy Perrier\u0026nbsp;; All authors have critically revised the final version of the manuscript and have approved its current version.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003e Authors would like to thank the clinical research department and the medical oncology department of the Centre Fran\u0026ccedil;ois Baclesse for their help in patient recruitment, the Interdisciplinary Center for Virtual Reality (CIREVE) in Caen (Normandy, France) for their technical support, and all the participants for their active contribution to these results. The Northwest Data Center (CTD-CNO) is acknowledged for managing the data.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEuropean Cancer and Cognition Consortium (ECCC), Sleurs, C., Amidi, A., Wu, L. M.,Kiesl, D., Zimmer, P., Lange, M., Rogiers, A., Giffard, B., Binarelli, G., Borghgraef,C., Deprez, S., Duivon, M., De Ruiter, M., Schagen, S., Ahmed-Lecheheb, D., Castel,H., Buskbjerg, C. R., Dos Santos, M., Joly, F., \u0026hellip; Perrier, J. (2022). 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Support Care Cancer janv\u003c/em\u003e. \u003cb\u003e21\u003c/b\u003e (1), 43\u0026ndash;51 (2013).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFiorentino, L. \u0026amp; Ancoli-Israel, S. Insomnia and its treatment in women with breast cancer. \u003cem\u003eSleep. Med. Rev. d\u0026eacute;c\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e (6), 419\u0026ndash;429 (2006).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"hypoxia, sleep disturbances, breast cancer, cognitive function, cancer-related cognitive impairments","lastPublishedDoi":"10.21203/rs.3.rs-6016528/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6016528/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCognitive complaints are common in breast cancer (BC). Previous studies have linked sleep-disordered breathing (SDB) to cognitive decline in the general population, highlighting hypoxia as a key factor in cognitive decline severity. This link is understudied in BC patients. We investigated the association between nocturnal hypoxia and cognitive performance in 35 BC patients compared to 21 healthy controls (HC; mean ages: 61.6 ± 5.3 and 62.6 ± 4.3, respectively) using in-home ambulatory polysomnography, including oximeter to record oxygen saturation. All participants completed questionnaires and cognitive tests. Non-parametric Wilcoxon tests were conducted to compare the two groups and multivariable models to measure the association between hypoxia and cognitive performance, adjusting for anxiety and depression. Our results showed more frequent nocturnal hypoxia and more cognitive complaints in BC patients compared to HCs (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05). However, cognitive tests did not show significant impairment in the BC group, and no significant association was found between nocturnal hypoxia and cognitive performance. Our patients were treated with radiotherapy and/or endocrine therapy, but without chemotherapy, which may explain their normal cognitive scores despite subjective cognitive complaints. Nocturnal hypoxia is more prevalent in BC patients than in HCs, but it may not be the primary factor influencing cognitive performance in this population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e NCT03420105, registered: January 10, 2018\u003c/p\u003e","manuscriptTitle":"Links between nocturnal hypoxia and cognitive function in breast cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 12:08:13","doi":"10.21203/rs.3.rs-6016528/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-10-29T10:35:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-28T09:01:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"64177536530382793818506156666162279418","date":"2025-10-28T08:18:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-27T23:29:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-24T09:39:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-10-21T09:33:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3898312a-8591-4050-afd0-c779b8045393","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":57008294,"name":"Biological sciences/Cancer/Breast cancer"},{"id":57008295,"name":"Biological sciences/Cancer/Cancer therapy"},{"id":57008296,"name":"Biological sciences/Cancer"},{"id":57008297,"name":"Biological sciences/Psychology"}],"tags":[],"updatedAt":"2025-12-01T16:07:50+00:00","versionOfRecord":{"articleIdentity":"rs-6016528","link":"https://doi.org/10.1038/s41598-025-26591-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-11-27 15:58:21","publishedOnDateReadable":"November 27th, 2025"},"versionCreatedAt":"2025-10-29 12:08:13","video":"","vorDoi":"10.1038/s41598-025-26591-z","vorDoiUrl":"https://doi.org/10.1038/s41598-025-26591-z","workflowStages":[]},"version":"v1","identity":"rs-6016528","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6016528","identity":"rs-6016528","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}