Respiratory Physiology & Neurobiology 201 (2014) 31–33
Contents lists available at ScienceDirect
Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol
Short communication
Gait abnormalities in obstructive sleep apnea and impact of continuous positive airway pressure G. Allali a,b,∗ , S. Perrig c , M. Cleusix a , F.R. Herrmann d , D. Adler e , G. Gex e , S. Armand f , J.P. Janssens e , J.L. Pepin c,g , F. Assal a a
Department of Neurology, Geneva University Hospitals and University of Geneva, Switzerland Department of Neurology, Division of Cognitive and Motor Aging, Albert Einstein College of Medicine, Bronx, NY, USA c Sleep Research Laboratory, Geneva University Hospital and University of Geneva, Switzerland d Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospital and University of Geneva, Switzerland e Division of Pulmonary Diseases, Geneva University Hospital and University of Geneva, Switzerland f Willy Taillard Laboratory of Kinesiology, Geneva University Hospitals and Geneva University, Switzerland g Univ. Grenoble Alpes, HP2, Inserm, HP2 (U1042), 38043 Grenoble, France b
a r t i c l e
i n f o
Article history: Accepted 21 June 2014 Available online 4 July 2014 Keywords: Gait disorders/ataxia Obstructive sleep apnea Continuous positive airway pressure
a b s t r a c t We aimed to determine the effect of continuous positive airway pressure (CPAP) on gait in obstructive sleep apnea (OSA) patients. Gait during single and dual tasks was recorded in 15 OSA patients at baseline and after 8 weeks of CPAP therapy. Step and stance time improved after CPAP. We showed a specific dual-task effect in the condition of verbal fluency. Eight weeks of CPAP seems to improve gait of OSA patients that are specifically disturbed by the dual task of verbal fluency. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Obstructive sleep apnea syndrome (OSA) is a highly prevalent sleep disorder that affects 5–20% of the population. It is a growing health concern worldwide, due to the associated increased risk of cardiovascular morbidity and mortality. The periodic upper airway collapse occurring during sleep in OSA patients induces chronic intermittent hypoxia and sleep fragmentation, which are thought to promote cardiovascular and cerebrovascular diseases and brain insult through oxidative stress, sympathetic activation, and systemic and vascular inflammation (Young et al., 2009). Excessive daytime sleepiness and impaired functioning in daily activities are the dominating complaints. Neurocognitive studies revealed the impact of OSA in many cognitive domains: attention/vigilance, executive functions, or memory (Kielb et al., 2012). Continuous positive airway pressure (CPAP), the most effective and widely used treatment, resulted in mild improvement in
∗ Corresponding author at: Department of Neurology, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva, Switzerland. Tel.: +41 22 372 83 02; fax: +41 22 372 83 33. E-mail addresses: [email protected], [email protected] (G. Allali). http://dx.doi.org/10.1016/j.resp.2014.06.012 1569-9048/© 2014 Elsevier B.V. All rights reserved.
frontal executive functions (FEF) in severe OSA patients and recent RCT have suggested that CPAP may reduce decline of cognitive functions in mild cognitive impairment (Kushida et al., 2012). Gait is traditionally described as an automatic motor activity independent from cognitive functions. However, in the past decades, many reports have shown the importance of executive functions in gait control, using the paradigm of dual tasking (YogevSeligmann et al., 2008), which requires the subject to perform a cognitive, attention-demanding task while walking. This interference of the attention-demanding task with walking suggests that both tasks rely on the same functional subsystem, and that gait also requires attention (Woollacott and Shumway-Cook, 2002). Although substantial data suggest that FEF are involved in gait control (Allali et al., 2007), there is still no data regarding the effect of CPAP on gait in OSA patients. Based on the improvement of FEF after CPAP treatment (Kielb et al., 2012) and the close relationship between gait and FEF (Yogev-Seligmann et al., 2008), we hypothesized that CPAP would improve gait parameters in patients with OSA. Using quantitative gait measurement including dual task, we assessed patients at baseline and after 8 weeks of conducted CPAP treatment. The goal of this pilot study was to compare gait parameters during single walking task and dual tasking before and after CPAP treatment.
32
G. Allali et al. / Respiratory Physiology & Neurobiology 201 (2014) 31–33
2. Methods 2.1. Participants Fifteen consecutive newly diagnosed OSA patients (mean age: 51.9 ± 7.6 years; % female: 20; BMI: 31.1 ± 5.0 kg/m2 , Epworth sleepiness scale: 11.3 ± 4.1; AHI: 57.0 ± 31.3) were prospectively included in this longitudinal study at Sleep Research Laboratory of Geneva University Hospitals. OSA diagnosis was based on full nocturnal polysomnography performed according to the AASM guidelines (Berry et al., 2012). The patients underwent a neurological and medical examination, as well as a clinical interview including the number of drugs taken per day, behavioral and cognitive assessment. Epworth sleepiness scale, fatigue severity scale and Beck depression inventory were also assessed during the medical interview. Exclusion criteria were acute medical illness in the past months; neurological and psychiatric diseases; orthopedic, rheumatologic or any sensory conditions affecting normal walking. Participants provided written informed consent to the protocol, which was approved by the Geneva University Hospitals ethics committee. Clinical trials registration number is NCT02061046. 2.2. Gait recordings Participants were evaluated at baseline and after 8 weeks of CPAP treatment. The time needed to achieve the 10 m walking distance were recorded using SMTEC® system (SMTEC® , Sport & Medical Technologies SA, Nyon, Switzerland) which consists of two footswitches providing a continuous measurement of temporal step parameters (Beauchet et al., 2008). This system includes a pair of innersoles fitted inside the subject’s shoes. Each subject completed one trial for each walking condition. Gait velocity and temporal gait parameters for all walking conditions were determined during steady-state walking. The order of gait analysis procedure was randomized in order to minimize learning effect and included: walking only; forward counting while walking, backward counting 1 by 1 from 50 to 1 while walking; and categorical verbal fluency (naming animals) while walking. Before testing, a trained evaluator gave standardized verbal instructions. For dual-tasking, the subjects were asked to walk and to do the dual task at the best of their capacity without any task prioritization.
Table 1 Bivariate linear regressions showing the association between gait parameters (independent variable) and types of dual task (dependant variable) adjusted for CPAP treatment visit.
Gait velocity Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit Step time Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit Swing time Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit Stance time Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit
Coef. ˇ
95% CI
p-value
1.00 0.0251 0.0052 −0.1660 0.0016
– [−0.029;0.079] [−0.061;0.072] [−0.269;−0.063] [−0.074;−0.077]
– 0.939 0.087 0.004a 0.965
1.00 −0.0005 0.0237 0.0867 −0.0149
– [−0.015;0.014] [−0.003;0.051] [0.040;0.133] [−0.029;−0.001]
– 0.939 0.087 0.001a 0.039
1.00 0.0046 0.0231 0.0779 −0.0034
– [−0.009;0.018] [−0.001;0.0466] [0.025;0.130] [−0.017;0.010]
– 0.481 0.055 0.001a 0.598
1.00 −0.0047 0.0232 0.1057 −0.0270
– [−0.024;0.015] [−0.010;0.056] [0.050;0.161] [−0.048;−0.006]
– 0.612 0.151 0.001a 0.016
CPAP, continuous positive airway pressure; FC, forward counting; BC, backward counting; VF, verbal fluency. a Survive the Benjamini and Hochberg corrected significance threshold (q = 0.0125).
For dual tasking, we also found a significant association between worse walking performance in all measured gait parameters (velocity, step, swing and stance time) and the dual task of categorical verbal fluency (p = 0.004, p = 0.001, p = 0.001, p = 0.001; respectively) (Table 1). For the other dual task conditions, we did not observe any significant association, although we noted a trend for the backward counting condition. Illustration of the gait velocity evolution of a study participant is presented in Fig. 1. Quantitative pre and post CPAP visits gait parameters are provided in a supplemental table.
2.3. Statistics Subjects’ characteristics were described using means and standard deviations or frequencies and percentages, as appropriate. Bivariate linear regressions were used to examine the association between gait parameters (independent variable) and the type of dual task (dependent variable) adjusted for post CPAP visit. pvalues less than 0.05 were considered statistically significant. To control for the false discovery rate associated with multiple statistical comparisons we computed a corrected significance level according to the method of Benjamini and Hochberg, implemented with a spreadsheet developed by Manuel Weinkauf available at http://www.marum.de/en/Leere Seite 5.html#Section12094. pvalues less than 0.0125 were considered statistically significant after applying the Benjamini and Hochberg correction (Benjamini and Hochberg, 1995). All statistics were performed using the Stata Statistical Software, version 10.1.
Gait velocity [m/s]
Before CPAP
1.5
After CPAP
1
0.5
0 Normal Walking
Walking while forward counting
Walking while backward counting
Walking while verbal fluency
3. Results After 8 weeks of CPAP treatment, we observed a significant improvement of step time (p = 0.039) and stance time (p = 0.016) in the bivariate regression model (Table 1).
Fig. 1. Gait velocity evolution in a study participant. Illustration of the gait velocity evolution in a patient with obstructive sleep apnea syndrome before (gray) and after 8 weeks (black) of continuous positive airway pressure (CPAP) treatment during the four walking conditions (normal walking, walking while forward counting, walking while backward counting, and walking while verbal fluency.
G. Allali et al. / Respiratory Physiology & Neurobiology 201 (2014) 31–33
4. Discussion We tested in this pilot study the hypothesis that CPAP treatment in OSA patients would improve temporal gait parameters. Step time and stance time were associated with a significant improvement after 8 weeks of CPAP treatment. These findings show, for the first time, that CPAP therapy is associated with an improvement of gait in OSA patients. Furthermore, we found that the dual task of categorical verbal fluency was specifically associated with worse temporal gait parameters. Gait modifications during dual-tasking are interpreted as the involvement of attention and FEF while walking, attesting a supraspinal control of gait, that could be disturbed in various pathological conditions affecting basal ganglia, frontal regions or their reciprocal connections (frontosubcortical circuits) (YogevSeligmann et al., 2008). In OSA syndrome, different mechanisms underlying cognitive impairment have been proposed: daytime somnolence, intermittent hypoxemia, sleep fragmentation or circadian disruption (Kielb et al., 2012). In comparison with previous studies including gait speed measurement in middle-aged participants (gait speed: 1.37 ± 0.14 m/s) (Allali et al., 2014), OSA patients presented decreased gait speed even during single tasking (gait speed: 1.12 ± 0.14 m/s). OSA syndrome is associated with brain white matter changes and silent strokes (Cho et al., 2013). Furthermore, metabolic brain changes have been described in the frontal regions in OSA patients and little changes have been documented after CPAP therapy (O’Donoghue et al., 2012). These metabolic and morphological brain changes described in the frontal lobes of OSA patients and their modification after CPAP treatment could contribute to the dual task effect and the improvement of temporal gait parameters after CPAP therapy shown in the present study. The strong relationship between attention and respiratory control highlights the neural networks between the brainstem respiratory complex and the suprapontine centers for breathing control (Gallego et al., 1996; Shea, 1996). Interestingly, similar “competitive” interactions between cortical breathing control and cognition have been documented in patients with congenital central hypoventilation syndrome (Ondine’s curse syndrome). In these patients, continuous cortical activation while awake may interfere with attention demanding tasks. Patients often report that this phenomenon can be reversed with the use of mechanical ventilation (Tremoureux et al., 2014). The small sample size and the absence of a matched control untreated group are the two main limitations of this pilot study. A baseline comparison between cognitive performances of OSA patients and healthy participants would have been informative to better understand the underlying mechanisms sustaining the relationship between gait control and brain functioning. This strongly supports a randomized controlled trial including a sham CPAP group. 5. Conclusion Temporal gait parameters seem to improve after 8-weeks of CPAP treatment in OSA patients. Furthermore, we found specific gait changes in dual task condition involving categorical verbal fluency. These data highlight that the close interaction between gait
33
and cognition is disturbed in OSA syndrome. In addition to classical metrics like apnea–hypopnea index and daytime sleepiness, gait improvement could represent a new objective outcome to assess neurocognitive CPAP effectiveness in OSA patients. Funding Supported by a Geneva University Hospitals Grant (PRD 10-II-7). Disclosures G. Allali, S. Perrig, M. Cleusix, F.R. Herrmann, D. Adler, G. Gex, S. Armand, J.P. Janssens, J.L. Pepin, F. Assal report no disclosures. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/j.resp.2014.06.012. References Allali, G., Kressig, R.W., Assal, F., Herrmann, F.R., Dubost, V., Beauchet, O., 2007. Changes in gait while backward counting in demented older adults with frontal lobe dysfunction. Gait Posture 26, 572–576. Allali, G., Laidet, M., Assal, F., Armand, S., Lalive, P.H., 2014. Walking while talking in patients with multiple sclerosis: the impact of specific cognitive loads. Neurophysiol. Clin. 44, 87–93. Beauchet, O., Herrmann, F.R., Grandjean, R., Dubost, V., Allali, G., 2008. Concurrent validity of SMTEC footswitches system for the measurement of temporal gait parameters. Gait Posture 27, 156–159. Benjamini, Y., Hochberg, Y., 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Statist. Soc. B 57, 289–300. Berry, R.B., Budhiraja, R., Gottlieb, D.J., Gozal, D., Iber, C., Kapur, V.K., Marcus, C.L., Mehra, R., Parthasarathy, S., Quan, S.F., Redline, S., Strohl, K.P., Davidson Ward, S.L., Tangredi, M.M., American Academy of Sleep Medicine, 2012. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin. Sleep Med. 8, 597–619. Cho, E.R., Kim, H., Seo, H.S., Suh, S., Lee, S.K., Shin, C., 2013. Obstructive sleep apnea as a risk factor for silent cerebral infarction. J. Sleep Res. 22, 452–458. Gallego, J., Denot-Ledunois, S., Vardon, G., Perruchet, P., 1996. Ventilatory responses to imagined exercise. Psychophysiology 33, 711–719. Kielb, S.A., Ancoli-Israel, S., Rebok, G.W., Spira, A.P., 2012. Cognition in obstructive sleep apnea–hypopnea syndrome (OSAS): current clinical knowledge and the impact of treatment. Neuromolecular Med. 14, 180–193. Kushida, C.A., Nichols, D.A., Holmes, T.H., Quan, S.F., Walsh, J.K., Gottlieb, D.J., Simon Jr., R.D., Guilleminault, C., White, D.P., Goodwin, J.L., Schweitzer, P.K., Leary, E.B., Hyde, P.R., Hirshkowitz, M., Green, S., McEvoy, L.K., Chan, C., Gevins, A., Kay, G.G., Bloch, D.A., Crabtree, T., Dement, W.C., 2012. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep 35, 1593–1602. O’Donoghue, F.J., Wellard, R.M., Rochford, P.D., Dawson, A., Barnes, M., Ruehland, W.R., Jackson, M.L., Howard, M.E., Pierce, R.J., Jackson, G.D., 2012. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment. Sleep 35, 41–48. Shea, S.A., 1996. Behavioural and arousal-related influences on breathing in humans. Exp. Physiol. 81, 1–26. Tremoureux, L., Raux, M., Hudson, A.L., Ranohavimparany, A., Straus, C., Similowski, T., 2014. Does the supplementary motor area keep patients with Ondine’s curse syndrome breathing while awake? PLoS One 9, e84534. Woollacott, M., Shumway-Cook, A., 2002. Attention and the control of posture and gait: a review of an emerging area of research. Gait Posture 16, 1–14. Yogev-Seligmann, G., Hausdorff, J.M., Giladi, N., 2008. The role of executive function and attention in gait. Mov. Disord., 329–342. Young, T., Palta, M., Dempsey, J., Peppard, P.E., Nieto, F.J., Hla, K.M., 2009. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort Study. WMJ 108, 246–249.
Contents lists available at ScienceDirect
Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol
Short communication
Gait abnormalities in obstructive sleep apnea and impact of continuous positive airway pressure G. Allali a,b,∗ , S. Perrig c , M. Cleusix a , F.R. Herrmann d , D. Adler e , G. Gex e , S. Armand f , J.P. Janssens e , J.L. Pepin c,g , F. Assal a a
Department of Neurology, Geneva University Hospitals and University of Geneva, Switzerland Department of Neurology, Division of Cognitive and Motor Aging, Albert Einstein College of Medicine, Bronx, NY, USA c Sleep Research Laboratory, Geneva University Hospital and University of Geneva, Switzerland d Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospital and University of Geneva, Switzerland e Division of Pulmonary Diseases, Geneva University Hospital and University of Geneva, Switzerland f Willy Taillard Laboratory of Kinesiology, Geneva University Hospitals and Geneva University, Switzerland g Univ. Grenoble Alpes, HP2, Inserm, HP2 (U1042), 38043 Grenoble, France b
a r t i c l e
i n f o
Article history: Accepted 21 June 2014 Available online 4 July 2014 Keywords: Gait disorders/ataxia Obstructive sleep apnea Continuous positive airway pressure
a b s t r a c t We aimed to determine the effect of continuous positive airway pressure (CPAP) on gait in obstructive sleep apnea (OSA) patients. Gait during single and dual tasks was recorded in 15 OSA patients at baseline and after 8 weeks of CPAP therapy. Step and stance time improved after CPAP. We showed a specific dual-task effect in the condition of verbal fluency. Eight weeks of CPAP seems to improve gait of OSA patients that are specifically disturbed by the dual task of verbal fluency. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Obstructive sleep apnea syndrome (OSA) is a highly prevalent sleep disorder that affects 5–20% of the population. It is a growing health concern worldwide, due to the associated increased risk of cardiovascular morbidity and mortality. The periodic upper airway collapse occurring during sleep in OSA patients induces chronic intermittent hypoxia and sleep fragmentation, which are thought to promote cardiovascular and cerebrovascular diseases and brain insult through oxidative stress, sympathetic activation, and systemic and vascular inflammation (Young et al., 2009). Excessive daytime sleepiness and impaired functioning in daily activities are the dominating complaints. Neurocognitive studies revealed the impact of OSA in many cognitive domains: attention/vigilance, executive functions, or memory (Kielb et al., 2012). Continuous positive airway pressure (CPAP), the most effective and widely used treatment, resulted in mild improvement in
∗ Corresponding author at: Department of Neurology, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva, Switzerland. Tel.: +41 22 372 83 02; fax: +41 22 372 83 33. E-mail addresses: [email protected], [email protected] (G. Allali). http://dx.doi.org/10.1016/j.resp.2014.06.012 1569-9048/© 2014 Elsevier B.V. All rights reserved.
frontal executive functions (FEF) in severe OSA patients and recent RCT have suggested that CPAP may reduce decline of cognitive functions in mild cognitive impairment (Kushida et al., 2012). Gait is traditionally described as an automatic motor activity independent from cognitive functions. However, in the past decades, many reports have shown the importance of executive functions in gait control, using the paradigm of dual tasking (YogevSeligmann et al., 2008), which requires the subject to perform a cognitive, attention-demanding task while walking. This interference of the attention-demanding task with walking suggests that both tasks rely on the same functional subsystem, and that gait also requires attention (Woollacott and Shumway-Cook, 2002). Although substantial data suggest that FEF are involved in gait control (Allali et al., 2007), there is still no data regarding the effect of CPAP on gait in OSA patients. Based on the improvement of FEF after CPAP treatment (Kielb et al., 2012) and the close relationship between gait and FEF (Yogev-Seligmann et al., 2008), we hypothesized that CPAP would improve gait parameters in patients with OSA. Using quantitative gait measurement including dual task, we assessed patients at baseline and after 8 weeks of conducted CPAP treatment. The goal of this pilot study was to compare gait parameters during single walking task and dual tasking before and after CPAP treatment.
32
G. Allali et al. / Respiratory Physiology & Neurobiology 201 (2014) 31–33
2. Methods 2.1. Participants Fifteen consecutive newly diagnosed OSA patients (mean age: 51.9 ± 7.6 years; % female: 20; BMI: 31.1 ± 5.0 kg/m2 , Epworth sleepiness scale: 11.3 ± 4.1; AHI: 57.0 ± 31.3) were prospectively included in this longitudinal study at Sleep Research Laboratory of Geneva University Hospitals. OSA diagnosis was based on full nocturnal polysomnography performed according to the AASM guidelines (Berry et al., 2012). The patients underwent a neurological and medical examination, as well as a clinical interview including the number of drugs taken per day, behavioral and cognitive assessment. Epworth sleepiness scale, fatigue severity scale and Beck depression inventory were also assessed during the medical interview. Exclusion criteria were acute medical illness in the past months; neurological and psychiatric diseases; orthopedic, rheumatologic or any sensory conditions affecting normal walking. Participants provided written informed consent to the protocol, which was approved by the Geneva University Hospitals ethics committee. Clinical trials registration number is NCT02061046. 2.2. Gait recordings Participants were evaluated at baseline and after 8 weeks of CPAP treatment. The time needed to achieve the 10 m walking distance were recorded using SMTEC® system (SMTEC® , Sport & Medical Technologies SA, Nyon, Switzerland) which consists of two footswitches providing a continuous measurement of temporal step parameters (Beauchet et al., 2008). This system includes a pair of innersoles fitted inside the subject’s shoes. Each subject completed one trial for each walking condition. Gait velocity and temporal gait parameters for all walking conditions were determined during steady-state walking. The order of gait analysis procedure was randomized in order to minimize learning effect and included: walking only; forward counting while walking, backward counting 1 by 1 from 50 to 1 while walking; and categorical verbal fluency (naming animals) while walking. Before testing, a trained evaluator gave standardized verbal instructions. For dual-tasking, the subjects were asked to walk and to do the dual task at the best of their capacity without any task prioritization.
Table 1 Bivariate linear regressions showing the association between gait parameters (independent variable) and types of dual task (dependant variable) adjusted for CPAP treatment visit.
Gait velocity Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit Step time Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit Swing time Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit Stance time Control (normal walking) Walking while FC Walking while BC Walking while VF CPAP treatment visit
Coef. ˇ
95% CI
p-value
1.00 0.0251 0.0052 −0.1660 0.0016
– [−0.029;0.079] [−0.061;0.072] [−0.269;−0.063] [−0.074;−0.077]
– 0.939 0.087 0.004a 0.965
1.00 −0.0005 0.0237 0.0867 −0.0149
– [−0.015;0.014] [−0.003;0.051] [0.040;0.133] [−0.029;−0.001]
– 0.939 0.087 0.001a 0.039
1.00 0.0046 0.0231 0.0779 −0.0034
– [−0.009;0.018] [−0.001;0.0466] [0.025;0.130] [−0.017;0.010]
– 0.481 0.055 0.001a 0.598
1.00 −0.0047 0.0232 0.1057 −0.0270
– [−0.024;0.015] [−0.010;0.056] [0.050;0.161] [−0.048;−0.006]
– 0.612 0.151 0.001a 0.016
CPAP, continuous positive airway pressure; FC, forward counting; BC, backward counting; VF, verbal fluency. a Survive the Benjamini and Hochberg corrected significance threshold (q = 0.0125).
For dual tasking, we also found a significant association between worse walking performance in all measured gait parameters (velocity, step, swing and stance time) and the dual task of categorical verbal fluency (p = 0.004, p = 0.001, p = 0.001, p = 0.001; respectively) (Table 1). For the other dual task conditions, we did not observe any significant association, although we noted a trend for the backward counting condition. Illustration of the gait velocity evolution of a study participant is presented in Fig. 1. Quantitative pre and post CPAP visits gait parameters are provided in a supplemental table.
2.3. Statistics Subjects’ characteristics were described using means and standard deviations or frequencies and percentages, as appropriate. Bivariate linear regressions were used to examine the association between gait parameters (independent variable) and the type of dual task (dependent variable) adjusted for post CPAP visit. pvalues less than 0.05 were considered statistically significant. To control for the false discovery rate associated with multiple statistical comparisons we computed a corrected significance level according to the method of Benjamini and Hochberg, implemented with a spreadsheet developed by Manuel Weinkauf available at http://www.marum.de/en/Leere Seite 5.html#Section12094. pvalues less than 0.0125 were considered statistically significant after applying the Benjamini and Hochberg correction (Benjamini and Hochberg, 1995). All statistics were performed using the Stata Statistical Software, version 10.1.
Gait velocity [m/s]
Before CPAP
1.5
After CPAP
1
0.5
0 Normal Walking
Walking while forward counting
Walking while backward counting
Walking while verbal fluency
3. Results After 8 weeks of CPAP treatment, we observed a significant improvement of step time (p = 0.039) and stance time (p = 0.016) in the bivariate regression model (Table 1).
Fig. 1. Gait velocity evolution in a study participant. Illustration of the gait velocity evolution in a patient with obstructive sleep apnea syndrome before (gray) and after 8 weeks (black) of continuous positive airway pressure (CPAP) treatment during the four walking conditions (normal walking, walking while forward counting, walking while backward counting, and walking while verbal fluency.
G. Allali et al. / Respiratory Physiology & Neurobiology 201 (2014) 31–33
4. Discussion We tested in this pilot study the hypothesis that CPAP treatment in OSA patients would improve temporal gait parameters. Step time and stance time were associated with a significant improvement after 8 weeks of CPAP treatment. These findings show, for the first time, that CPAP therapy is associated with an improvement of gait in OSA patients. Furthermore, we found that the dual task of categorical verbal fluency was specifically associated with worse temporal gait parameters. Gait modifications during dual-tasking are interpreted as the involvement of attention and FEF while walking, attesting a supraspinal control of gait, that could be disturbed in various pathological conditions affecting basal ganglia, frontal regions or their reciprocal connections (frontosubcortical circuits) (YogevSeligmann et al., 2008). In OSA syndrome, different mechanisms underlying cognitive impairment have been proposed: daytime somnolence, intermittent hypoxemia, sleep fragmentation or circadian disruption (Kielb et al., 2012). In comparison with previous studies including gait speed measurement in middle-aged participants (gait speed: 1.37 ± 0.14 m/s) (Allali et al., 2014), OSA patients presented decreased gait speed even during single tasking (gait speed: 1.12 ± 0.14 m/s). OSA syndrome is associated with brain white matter changes and silent strokes (Cho et al., 2013). Furthermore, metabolic brain changes have been described in the frontal regions in OSA patients and little changes have been documented after CPAP therapy (O’Donoghue et al., 2012). These metabolic and morphological brain changes described in the frontal lobes of OSA patients and their modification after CPAP treatment could contribute to the dual task effect and the improvement of temporal gait parameters after CPAP therapy shown in the present study. The strong relationship between attention and respiratory control highlights the neural networks between the brainstem respiratory complex and the suprapontine centers for breathing control (Gallego et al., 1996; Shea, 1996). Interestingly, similar “competitive” interactions between cortical breathing control and cognition have been documented in patients with congenital central hypoventilation syndrome (Ondine’s curse syndrome). In these patients, continuous cortical activation while awake may interfere with attention demanding tasks. Patients often report that this phenomenon can be reversed with the use of mechanical ventilation (Tremoureux et al., 2014). The small sample size and the absence of a matched control untreated group are the two main limitations of this pilot study. A baseline comparison between cognitive performances of OSA patients and healthy participants would have been informative to better understand the underlying mechanisms sustaining the relationship between gait control and brain functioning. This strongly supports a randomized controlled trial including a sham CPAP group. 5. Conclusion Temporal gait parameters seem to improve after 8-weeks of CPAP treatment in OSA patients. Furthermore, we found specific gait changes in dual task condition involving categorical verbal fluency. These data highlight that the close interaction between gait
33
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