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Magnetic Resonance Spectroscopy and Neurocognitive Dysfunction in Obstructive Sleep Apnea before and after CPAP Treatment [fonte www.journalsleep.org VOLUME 35, ISSUE 01]



Fergal J. O'Donoghue, MBBCh, PhD1,2,4; R. Mark Wellard, BSc(hons), MSc, PhD2,3; Peter D. Rochford, B App Sci1; Andrew Dawson, BA (hons)1; Maree Barnes, MBBS1; Warren R. Ruehland, BSc(hons)1,4; Melinda L. Jackson, PhD1; Mark E. Howard, MBBS, PhD1,4; Robert J. Pierce, MBBS, MD1,4; Graeme D. Jackson, BSc, MBBS, MD2,4

1Institute for Breathing and Sleep, Austin Health, Heidelberg, Australia; 2Brain Research Institute, Florey Neuroscience Institutes, Heidelberg West, Australia; 3Queensland University of Technology, Brisbane, Australia; 4University of Melbourne, Parkville, Australia


Study Objectives:

To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA.


Observational, before and after CPAP treatment.


Two tertiary hospital research institutes.


30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM).

Measurements and Results:

Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = −0.39, corrected P = 0.033) and between % total sleep time at SpO2 < 90% and hippocampal Cho/Cr (r = −0.40, corrected P = 0.01).


OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.


O'Donoghue FJ; Wellard RM; Rochford PD; Dawson A; Barnes M; Ruehland WR; Jackson ML; Howard ME; Pierce RJ; Jackson GD. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment. SLEEP 2012;35(1):41-48.




02/12/2010 - Loud Snoring Predicts Metabolic Syndrome
By Cole Petrochko, Staff Writer, MedPage Today - Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Patients with sleep symptoms are at higher risk for developing metabolic syndrome, a prospective study found.


Difficulty falling asleep, snoring loudly, and unrefreshing sleep were significant predictors of metabolic syndrome (P<0.05). Snoring doubled the risk, while difficulty falling asleep increased the risk by 80%, Wendy Troxel, PhD, of the University of Pittsburgh, and colleagues reported in Sleep.

Loud snoring also was associated with doubled risks of other metabolic abnormalities, and remained a significant metabolic syndrome predictor after further apnea-hypopnea index (AHI) adjustment, whereas other sleep symptoms were only marginally significant, the researchers noted.



Action Points  

  • Explain that patients with sleep symptoms such as difficulty falling asleep, unrefreshing sleep, and loud snoring are at higher risk for developing metabolic syndrome.

The study evaluated 2,000 patients enrolled in an ongoing, community-based prospective heart health study. Patients were ages 45 to 74, lived in or around the Pittsburgh metropolitan area, and had no comorbidity limiting life expectancy to less than five years.

Exclusion criteria included non-black or non-white race, presence of metabolic syndrome or diabetes at baseline, and missing sleep or covariate data at baseline.

The final sample included 812 patients, with a subset of 294 patients agreeing to undergo further evaluation at home in a follow-up analysis adjusted for AHI.

The primary outcome was the presence or absence of metabolic syndrome at the three-year follow-up. Waist circumference, fasting glucose, and lipids were measured at baseline and annually for three years.

Patients were given the Insomnia Sleep Questionnaire and the Multivariable Apnea Prediction Questionnaire to evaluate sleep-disordered breathing and insomnia symptoms. Covariate measures included history of smoking, alcohol consumption, physical activeness, and depressive symptoms.

At the three year follow-up, 14% of patients developed metabolic syndrome. After adjustment for loud snoring, difficulty falling asleep remained a significant predictor (OR 1.78, 95% CI 1.05 to 3.02), while unrefreshing sleep showed marginal significance (OR 1.56, 95% CI 0.96 to 2.53).

The significant symptoms also were compared against the AHI. Only loud snoring remained significant as a predictor (OR 3.01, 95% CI 1.39 to 6.55), while difficulty falling asleep was marginal (OR 1.91, 95% CI 0.80 to 4.58).

Researchers noted the study was limited by self-reported sleep disturbance and lack of sleep duration measures. The AHI analysis was limited by small subsample size and the cross-sectional nature of the AHI assessment.

Healthcare professionals should look for common sleep symptoms while assessing a patient due to the measured health risks associated with some symptoms, the researchers concluded, adding that future research could look at subjective sleep complaints and psychological factors affecting patients' poor sleep related to cardiovascular morbidity and mortality.

Co-authors reported relationships with ResMed, Respironics, Actelion, Arena, Cephalon, Eli Lilly, GlaxoSmithKline, Merck, Neurocrine, Neurogen, Pfizer, sanofi-aventis, Sepracor, Servier, Somnus, Stress Eraser, Takeda, and Transcept.

Primary source: Sleep
Source reference:
Troxel WM "Sleep symptoms predict the development of the metabolic syndrome" SLEEP 2010; 33: 1633-1640.

[fonte medpagetoday.com]


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Reduced Brain Gray Matter Concentration in Patients With Obstructive Sleep Apnea Syndrome

Eun Yeon Joo, MD, PhD1; Woo Suk Tae, PhD2; Min Joo Lee, MS1; Jung Woo Kang, MD1; Hwan Seok Park, MD1; Jun Young Lee, MD1; Minah Suh, PhD3; Seung Bong Hong MD, PhD1

1Sleep Center, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; 2Neuroscience Research Institute, Kangwon National University College of Medicine, Chunchon City, Korea; 3Department of Biological Science, Sungkyunkwan University, Suwon, Korea

Study Objectives: To investigate differences in brain gray matter concentrations or volumes in patients with obstructive sleep apnea syndrome (OSA) and healthy volunteers.
Designs: Optimized voxel-based morphometry, an automated processing technique for MRI, was used to characterize structural differences in gray matter in newly diagnosed male patients.
Setting: University hospital
Patients and Participants: The study consisted of 36 male OSA and 31 non-apneic male healthy volunteers matched for age (mean age, 44.8 years).
Interventions: Using the t-test, gray matter differences were identified. The statistical significance level was set to a false discovery rate P < 0.05 with an extent threshold of kE > 200 voxels.
Measurements and Results: The mean apnea-hypopnea index (AHI) of patients was 52.5/ h. On visual inspection of MRI, no structural abnormalities were observed. Compared to healthy volunteers, the gray matter concentrations of OSA patients were significantly decreased in the left gyrus rectus, bilateral superior frontal gyri, left precentral gyrus, bilateral frontomarginal gyri, bilateral anterior cingulate gyri, right insular gyrus, bilateral caudate nuclei, bilateral thalami, bilateral amygdalo-hippocampi, bilateral inferior temporal gyri, and bilateral quadrangular and biventer lobules in the cerebellum (false discovery rate P < 0.05). Gray matter volume was not different between OSA patients and healthy volunteers.
Conclusions: The brain gray matter deficits may suggest that memory impairment, affective and cardiovascular disturbances, executive dysfunctions, and dysregulation of autonomic and respiratory control frequently found in OSA patients might be related to morphological differences in the brain gray matter areas.
Keywords: Obstructive sleep apnea, Brain, Gray matter concentration, MRI, Voxel based morphometry

Citation: Joo EY; Tae WS; Lee MJ; Kang JW; Park HS; Lee JY; Suh M; Hong SB. Reduced brain gray matter concentration in patients with obstructive sleep apnea syndrome. SLEEP 2010;33(2):235-241.


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Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea.

Department of Otorhinolaryngology, Institute of Clinical Medicine, University of Kuopio, Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland. henri.tuomilehto@kuh.fi

RATIONALE: Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA. OBJECTIVES: The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA. METHODS: Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements. MEASUREMENTS AND MAIN RESULTS: The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference. CONCLUSIONS: VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up. [fonte PubMed - indexed for MEDLINE]


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last update: 06.01.2012