Brain activation changes before and after PAP treatment in obstructive sleep apnea
Vincenza Castronovo, Nicola Canessa, Luigi Ferini Strambi, Mark S Aloia, Monica Consonni, Sara Marelli, Antonella Iadanza, Alice Bruschi, Andrea Falini, Stefano F Cappa, Vincenza Castronovo, Nicola Canessa, Luigi Ferini Strambi, Mark S Aloia, Monica Consonni, Sara Marelli, Antonella Iadanza, Alice Bruschi, Andrea Falini, Stefano F Cappa
Abstract
Study objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cognitive and functional deficits, most of which are corrected after positive airway pressure (PAP) treatment. Previous studies investigating the neural underpinnings of OSAS failed to provide consistent results both on the cerebral substrates underlying cognitive deficits and on the effect of treatment on these anomalies. The aims of the study were a) to investigate whether never-treated OSA patients demonstrated differences in brain activation compared to healthy controls during a cognitive task; and b) to investigate whether any improvements in cognitive functioning found in OSA patients after treatment reflected a change in the underlying cerebral activity.
Design: OSA patients and healthy controls underwent functional magnetic resonance imaging (fMRI) scanning. They were compared on performance and brain activation during a 2-back working-memory task. Patients were also re-evaluated after 3 months treatment with PAP. Cognitive functions were evaluated using neurocognitive tests. Sleepiness (ESS), mood (Beck Depression Inventory) and, quality-of-life (SF-36) were also assessed.
Setting: The Sleep Disorders Center and CERMAC at the Vita-Salute San Raffaele University.
Patients or participants: 17 OSA patients and 15 age- and education-matched healthy controls.
Interventions: PAP treatment for 3 months.
Measurements and results: Compared to controls, never-treated OSA patients showed increased activations in the left frontal cortex, medial precuneus, and hippocampus, and decreased activations in the caudal pons. OSA patients showed decreases in activation with treatment in the left inferior frontal gyrus and anterior cingulate cortex, and bilaterally in the hippocampus. Most neurocognitive domains, impaired at baseline, showed significant improvement after treatment.
Conclusions: OSA patients showed an overrecruitment of brain regions compared to controls, in the presence of the same level of performance on a working-memory task. Decreases of activation in prefrontal and hippocampal structures were observed after treatment in comparison to baseline. These findings may reflect a neural compensation mechanism in never-treated patients, which is reduced by effective treatment.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2737574/bin/aasm.32.9.1161a.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2737574/bin/aasm.32.9.1161b.jpg)
Figure 3
Common parametric effects of WM…
Figure 3
Common parametric effects of WM load in pretreatment and posttreatment OSA patients. From…
Figure 4
Differential parametric effects of WM…
Figure 4
Differential parametric effects of WM load in healthy controls, pretreatment OSA patients and…
Figure 5
Differential parametric effects of WM…
Figure 5
Differential parametric effects of WM load in healthy controls and posttreatment OSA patients.…
Figure 6
Reduced right lateral prefrontal activation…
Figure 6
Reduced right lateral prefrontal activation in both pre- and posttreatment OSA patients compared…
- Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment.Canessa N, Castronovo V, Cappa SF, Aloia MS, Marelli S, Falini A, Alemanno F, Ferini-Strambi L. Canessa N, et al. Am J Respir Crit Care Med. 2011 May 15;183(10):1419-26. doi: 10.1164/rccm.201005-0693OC. Epub 2010 Oct 29. Am J Respir Crit Care Med. 2011. PMID: 21037021
- White matter integrity in obstructive sleep apnea before and after treatment.Castronovo V, Scifo P, Castellano A, Aloia MS, Iadanza A, Marelli S, Cappa SF, Strambi LF, Falini A. Castronovo V, et al. Sleep. 2014 Sep 1;37(9):1465-75. doi: 10.5665/sleep.3994. Sleep. 2014. PMID: 25142557 Free PMC article. Clinical Trial.
- Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.Song X, Roy B, Kang DW, Aysola RS, Macey PM, Woo MA, Yan-Go FL, Harper RM, Kumar R. Song X, et al. Brain Behav. 2018 Jun;8(6):e00994. doi: 10.1002/brb3.994. Epub 2018 May 10. Brain Behav. 2018. PMID: 29749715 Free PMC article.
- Cognitive deficits in adults with obstructive sleep apnea compared to children and adolescents.Krysta K, Bratek A, Zawada K, Stepańczak R. Krysta K, et al. J Neural Transm (Vienna). 2017 Feb;124(Suppl 1):187-201. doi: 10.1007/s00702-015-1501-6. Epub 2016 Jan 4. J Neural Transm (Vienna). 2017. PMID: 26729362 Free PMC article. Review.
- A review of neurocognitive function and obstructive sleep apnea with or without daytime sleepiness.Zhou J, Camacho M, Tang X, Kushida CA. Zhou J, et al. Sleep Med. 2016 Jul;23:99-108. doi: 10.1016/j.sleep.2016.02.008. Epub 2016 Mar 2. Sleep Med. 2016. PMID: 27288049 Review.
- The Link between Obstructive Sleep Apnea and Neurocognitive Impairment: An Official American Thoracic Society Workshop Report.Lal C, Ayappa I, Ayas N, Beaudin AE, Hoyos C, Kushida CA, Kaminska M, Mullins A, Naismith SL, Osorio RS, Phillips CL, Parekh A, Stone KL, Turner AD, Varga AW. Lal C, et al. Ann Am Thorac Soc. 2022 Aug;19(8):1245-1256. doi: 10.1513/AnnalsATS.202205-380ST. Ann Am Thorac Soc. 2022. PMID: 35913462 Free PMC article.
- Increased Levels of Plasma Alzheimer's Disease Biomarkers and Their Associations with Brain Structural Changes and Carotid Intima-Media Thickness in Cognitively Normal Obstructive Sleep Apnea Patients.Chen YS, Chen MH, Wang PM, Lu CH, Chen HL, Lin WC. Chen YS, et al. Diagnostics (Basel). 2022 Jun 22;12(7):1522. doi: 10.3390/diagnostics12071522. Diagnostics (Basel). 2022. PMID: 35885428 Free PMC article.
- Intrinsic network changes associated with cognitive impairment in patients with hearing loss and tinnitus: a resting-state functional magnetic resonance imaging study.Ma X, Li W, Wang Q, He X, Qu X, Li T, Zhang L, Liu Z. Ma X, et al. Ann Transl Med. 2022 Jun;10(12):690. doi: 10.21037/atm-22-2135. Ann Transl Med. 2022. PMID: 35845541 Free PMC article.
- 18F-FDG PET, cognitive functioning, and CSF biomarkers in patients with obstructive sleep apnoea before and after continuous positive airway pressure treatment.Fernandes M, Mari L, Chiaravalloti A, Paoli B, Nuccetelli M, Izzi F, Giambrone MP, Camedda R, Bernardini S, Schillaci O, Mercuri NB, Placidi F, Liguori C. Fernandes M, et al. J Neurol. 2022 Oct;269(10):5356-5367. doi: 10.1007/s00415-022-11182-z. Epub 2022 May 24. J Neurol. 2022. PMID: 35608659 Free PMC article.
- Cognition effectiveness of continuous positive airway pressure treatment in obstructive sleep apnea syndrome patients with cognitive impairment: a meta-analysis.Jiang X, Wang Z, Hu N, Yang Y, Xiong R, Fu Z. Jiang X, et al. Exp Brain Res. 2021 Dec;239(12):3537-3552. doi: 10.1007/s00221-021-06225-2. Epub 2021 Sep 21. Exp Brain Res. 2021. PMID: 34546386
- Adult
- Brain / physiology
- Brain / physiopathology*
- Brain Mapping / methods*
- Cognition
- Follow-Up Studies
- Humans
- Image Processing, Computer-Assisted / methods
- Magnetic Resonance Imaging / methods
- Male
- Memory, Short-Term
- Neuropsychological Tests / statistics & numerical data
- Polysomnography / methods
- Positive-Pressure Respiration / methods*
- Sleep Apnea, Obstructive / physiopathology*
- Sleep Apnea, Obstructive / therapy*
- Task Performance and Analysis
- Full Text Sources
- Medical
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![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2737574/bin/aasm.32.9.1161c.jpg)
Figure 4
Differential parametric effects of WM…
Figure 4
Differential parametric effects of WM load in healthy controls, pretreatment OSA patients and…
Figure 5
Differential parametric effects of WM…
Figure 5
Differential parametric effects of WM load in healthy controls and posttreatment OSA patients.…
Figure 6
Reduced right lateral prefrontal activation…
Figure 6
Reduced right lateral prefrontal activation in both pre- and posttreatment OSA patients compared…
- Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment.Canessa N, Castronovo V, Cappa SF, Aloia MS, Marelli S, Falini A, Alemanno F, Ferini-Strambi L. Canessa N, et al. Am J Respir Crit Care Med. 2011 May 15;183(10):1419-26. doi: 10.1164/rccm.201005-0693OC. Epub 2010 Oct 29. Am J Respir Crit Care Med. 2011. PMID: 21037021
- White matter integrity in obstructive sleep apnea before and after treatment.Castronovo V, Scifo P, Castellano A, Aloia MS, Iadanza A, Marelli S, Cappa SF, Strambi LF, Falini A. Castronovo V, et al. Sleep. 2014 Sep 1;37(9):1465-75. doi: 10.5665/sleep.3994. Sleep. 2014. PMID: 25142557 Free PMC article. Clinical Trial.
- Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.Song X, Roy B, Kang DW, Aysola RS, Macey PM, Woo MA, Yan-Go FL, Harper RM, Kumar R. Song X, et al. Brain Behav. 2018 Jun;8(6):e00994. doi: 10.1002/brb3.994. Epub 2018 May 10. Brain Behav. 2018. PMID: 29749715 Free PMC article.
- Cognitive deficits in adults with obstructive sleep apnea compared to children and adolescents.Krysta K, Bratek A, Zawada K, Stepańczak R. Krysta K, et al. J Neural Transm (Vienna). 2017 Feb;124(Suppl 1):187-201. doi: 10.1007/s00702-015-1501-6. Epub 2016 Jan 4. J Neural Transm (Vienna). 2017. PMID: 26729362 Free PMC article. Review.
- A review of neurocognitive function and obstructive sleep apnea with or without daytime sleepiness.Zhou J, Camacho M, Tang X, Kushida CA. Zhou J, et al. Sleep Med. 2016 Jul;23:99-108. doi: 10.1016/j.sleep.2016.02.008. Epub 2016 Mar 2. Sleep Med. 2016. PMID: 27288049 Review.
- The Link between Obstructive Sleep Apnea and Neurocognitive Impairment: An Official American Thoracic Society Workshop Report.Lal C, Ayappa I, Ayas N, Beaudin AE, Hoyos C, Kushida CA, Kaminska M, Mullins A, Naismith SL, Osorio RS, Phillips CL, Parekh A, Stone KL, Turner AD, Varga AW. Lal C, et al. Ann Am Thorac Soc. 2022 Aug;19(8):1245-1256. doi: 10.1513/AnnalsATS.202205-380ST. Ann Am Thorac Soc. 2022. PMID: 35913462 Free PMC article.
- Increased Levels of Plasma Alzheimer's Disease Biomarkers and Their Associations with Brain Structural Changes and Carotid Intima-Media Thickness in Cognitively Normal Obstructive Sleep Apnea Patients.Chen YS, Chen MH, Wang PM, Lu CH, Chen HL, Lin WC. Chen YS, et al. Diagnostics (Basel). 2022 Jun 22;12(7):1522. doi: 10.3390/diagnostics12071522. Diagnostics (Basel). 2022. PMID: 35885428 Free PMC article.
- Intrinsic network changes associated with cognitive impairment in patients with hearing loss and tinnitus: a resting-state functional magnetic resonance imaging study.Ma X, Li W, Wang Q, He X, Qu X, Li T, Zhang L, Liu Z. Ma X, et al. Ann Transl Med. 2022 Jun;10(12):690. doi: 10.21037/atm-22-2135. Ann Transl Med. 2022. PMID: 35845541 Free PMC article.
- 18F-FDG PET, cognitive functioning, and CSF biomarkers in patients with obstructive sleep apnoea before and after continuous positive airway pressure treatment.Fernandes M, Mari L, Chiaravalloti A, Paoli B, Nuccetelli M, Izzi F, Giambrone MP, Camedda R, Bernardini S, Schillaci O, Mercuri NB, Placidi F, Liguori C. Fernandes M, et al. J Neurol. 2022 Oct;269(10):5356-5367. doi: 10.1007/s00415-022-11182-z. Epub 2022 May 24. J Neurol. 2022. PMID: 35608659 Free PMC article.
- Cognition effectiveness of continuous positive airway pressure treatment in obstructive sleep apnea syndrome patients with cognitive impairment: a meta-analysis.Jiang X, Wang Z, Hu N, Yang Y, Xiong R, Fu Z. Jiang X, et al. Exp Brain Res. 2021 Dec;239(12):3537-3552. doi: 10.1007/s00221-021-06225-2. Epub 2021 Sep 21. Exp Brain Res. 2021. PMID: 34546386
- Adult
- Brain / physiology
- Brain / physiopathology*
- Brain Mapping / methods*
- Cognition
- Follow-Up Studies
- Humans
- Image Processing, Computer-Assisted / methods
- Magnetic Resonance Imaging / methods
- Male
- Memory, Short-Term
- Neuropsychological Tests / statistics & numerical data
- Polysomnography / methods
- Positive-Pressure Respiration / methods*
- Sleep Apnea, Obstructive / physiopathology*
- Sleep Apnea, Obstructive / therapy*
- Task Performance and Analysis
- Full Text Sources
- Medical
- Research Materials
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Source: PubMed