Omar E. Burschtin

The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimers disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimers disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.

Acoustic rhinometry predicts tolerance of nasal continuous positive airway pressure : A pilot study

Background Nasal continuous positive airway pressure (nCPAP) is usually the first-line intervention for obstructive sleep apnea, but up to 50% of patients are unable to tolerate therapy because of discomfort–-usually nasal complaints. No factors have been definitively correlated with nCPAP tolerance, although nasal cross-sectional area has been correlated with the level of CPAP pressure, and nasal surgery improves nCPAP compliance. This study examined the relationship between nasal cross-sectional area and nCPAP tolerance. Methods We performed acoustic rhinometry on 34 obstructive sleep apnea patients at the time of the initial sleep study. Patients titrated to nCPAP were interviewed 18 months after starting therapy to determine CPAP tolerance. Demographic, polysomnographic, and nasal cross-sectional area data were compared between CPAP-tolerant and -intolerant patients. Results Between 13 tolerant and 12 intolerant patients, there were no significant differences in age, gender, body mass index, CPAP level, respiratory disturbance index, or subjective nasal obstruction. Cross-sectional area at the inferior turbinate differed significantly between the two groups (p = 0.03). This remained significant after multivariate analysis for possibly confounding variables. A cross-sectional area cutoff of 0.6 cm2 at the head of the inferior turbinate carried a sensitivity of 75% and specificity of 77% for CPAP intolerance in this patient group. Conclusion Nasal airway obstruction correlated with CPAP tolerance, supporting an important role for the nose in CPAP, and providing a physiological basis for improved CPAP compliance after nasal surgery. Objective nasal evaluation, but not the subjective report of nasal obstruction, may be helpful in the management of these patients.

Nasal obstruction and sleep-disordered breathing: a study using acoustic rhinometry.

Background The relationship between nasal airway function and sleep-disordered breathing (SDB) remains unclear. Although correction of nasal obstruction can significantly improve nighttime breathing in some patients, nasal obstruction may not play a role in all cases of SDB. An effective method of stratifying these patients is needed. Acoustic rhinometry (AR) is a reliable, noninvasive method of measuring the dimensions of the nasal airway. Methods In 44 patients, we performed acoustic rhinometric measurements of nasal airway cross-sectional area, followed by hospital-based polysomnography and nasal continuous positive airway pressure (nCPAP) level titration. We compared anatomic nasal obstruction to perceived nasal obstruction, as well as respiratory distress index and nCPAP titration level, using the Pearson correlation and multiple linear regression analysis within body mass index groups. Results Perceived nasal obstruction correlated significantly with objective anatomic obstruction as measured by AR (r = 0.45, p < 0.01). For certain subgroup analyses inpatients with a body mass index below 25, AR measurements correlated significantly with both nCPAP titration pressure (r = 0.85, p < 0.01) and respiratory distress index (r = 0.67, p = 0.03). Conclusion Nasal airway function may be a significant component of SDB in some patients, perhaps playing a larger role in patients who are not overweight. The best responders to nasal surgery for SDB may be nonoverweight patients with nasal obstruction. AR along with nasal examination may be helpful in the evaluation and treatment of the SDB patient.

Rapid risk stratification for obstructive sleep apnea, based on snoring severity and body mass index

Objective It is unclear whether all snoring patients require polysomnography, and there are no highly sensitive clinical predictors of sleep apnea. Our objective was to develop a simple clinical screening test for OSA in snoring patients. Study Design Prospective, IRB-approved study at a university sleep disorders center. Subjects and Methods In 211 patients undergoing polysomnography, snoring severity, Epworth sleepiness scale, body mass index, demographic, and sleep study data were collected. Receiver operating characteristic (ROC) analysis and Pearson correlation were used to develop a sensitive screening test for OSA. Results Snoring severity score (SSS) and BMI were the two most accurate predictors of OSA on the ROC curve. A bipartite threshold of SSS = 4 or BMI = 26 carried sensitivity of 97.4%, specificity of 40%, positive predictive value of 82.3%, and negative predictive value of 84.2% for moderate/severe OSA. Patients at high risk were those with BMI ≥32 (89% PPV) or SSS ≥7 (92% PPV). Conclusions The statistic most predictive of OSA was snoring severity. Combining this with BMI yielded a highly sensitive screening test for moderate/severe OSA. This clinical assessment may be useful in risk-stratifying patients for polysomnography and therapy, facilitating deferred work-up in low-risk patients and expedited therapy in high-risk patients.

Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals.

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimers disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimers disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.

Effects of aging on slow-wave sleep dynamics and human spatial navigational memory consolidation.

The consolidation of spatial navigational memory during sleep is supported by electrophysiological and behavioral evidence. The features of sleep that mediate this ability may change with aging, as percentage of slow-wave sleep is canonically thought to decrease with age, and slow waves are thought to help orchestrate hippocampal-neocortical dialog that supports systems level consolidation. In this study, groups of younger and older subjects performed timed trials before and after polysomnographically recorded sleep on a 3D spatial maze navigational task. Although younger subjects performed better than older subjects at baseline, both groups showed similar improvement across presleep trials. However, younger subjects experienced significant improvement in maze performance during sleep that was not observed in older subjects, without differences in morning psychomotor vigilance between groups. Older subjects had sleep quality marked by decreased amount of slow-wave sleep and increased fragmentation of slow-wave sleep, resulting in decreased slow-wave activity. Across all subjects, frontal slow-wave activity was positively correlated with both overnight change in maze performance and medial prefrontal cortical volume, illuminating a potential neuroanatomical substrate for slow-wave activity changes with aging and underscoring the importance of slow-wave activity in sleep-dependent spatial navigational memory consolidation.

REM-associated nasal obstruction: A study with acoustic rhinometry during sleep

Objective Obstructive sleep apnea events are more common in REM sleep, although there is no relationship between sleep phase and pharyngeal airway status. We studied the patency of the nasal airway during REM and non-REM sleep with the use of acoustic rhinometry. Methods Serial acoustic rhinometric assessment of nasal cross-sectional area was performed in 10 subjects, before sleep and during REM and non-REM sleep. All measurements were standardized to a decongested baseline with mean congestion factor (MCF). Results MCF in the seated position was 10.6% (±3.7) and increased with supine positioning to 16.2% (±2.3). In REM sleep, MCF was highest, at 22.3% (±1.7). In non-REM sleep, MCF was lowest, at 2.3% (±3.1). All interstage comparisons were statistically significant on repeated measures ANOVA (P < 0.05). Conclusion REM sleep is characterized by significant nasal congestion; non-REM sleep, by profound decongestion. This phenomenon may be attributable to REM-dependent variation in cerebral blood flow that affects nasal congestion via the internal carotid system. REM-induced nasal congestion, an indirect effect of augmented cerebral perfusion, may contribute to the higher frequency of obstructive events in REM sleep.

The interaction between sleep-disordered breathing and ApoE genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimers disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimers disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.