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Addition of frontal EEG to adult home sleep apnea testing: does a more accurate determination of sleep time make a difference?

Light, Matthew P; Casimire, Thalia N; Chua, Catherine; Koushyk, Viachaslau; Burschtin, Omar E; Ayappa, Indu; Rapoport, David M
RATIONALE/BACKGROUND:Home sleep apnea testing (HSAT) typically does not include electroencephalogram (EEG) monitoring for sleep assessment. In patients with insomnia and low sleep efficiency, overestimation of the sleep period can result from absence of EEG, which will reduce sleep disordered breathing (SDB) indices and may lead to a false-negative result. OBJECTIVE:To validate a single channel frontal EEG for scoring sleep versus wake against full EEG during polysomnography, and then to examine the utility of adding this single channel EEG to standard HSAT to prevent false-negative results. METHODS:), to calculate AHI4 and RDI and the effect on OSA diagnosis and severity. Analyses were repeated in 69 patients with poor sleep suggesting insomnia plus Epworth Sleepiness Scale < 7 as well as in 38 patients ultimately shown to have sleep efficiency < 70% on HSAT with EEG. MEASUREMENTS AND MAIN RESULTS/RESULTS:Single channel and full EEG during polysomnography agreed on sleep versus wake in 92-95% of all epochs. HSAT without EEG overestimated the sleep period by 20% (VST = 440 ± 76 min vs TST = 356 ± 82 min), had a false-negative rate of 8% by AHI4 criteria, and underestimated disease severity in 11% of all patients. Sub-group analysis of patients with subjective poor sleep suggesting insomnia did not change the results. Patients later shown to have low sleep efficiency had lower SDB indices and a 20.8% false negative rate of sleep apnea diagnosis. CONCLUSIONS:were moderate, suggesting utility for ruling out OSA, there was a specific subgroup in whom there were significant missed diagnoses. However, we were unable to identify this subgroup a priori.
PMID: 30311183
ISSN: 1522-1709
CID: 3335112

Addition Of Frontal Eeg To Home Sleep Apnea Testing To Diagnose Adult Obstructive Sleep Apnea: Does A More Accurate Determination Of Sleep Time Make A Difference? [Meeting Abstract]

Light, M; Casimire, T; Chua, C; Koushyk, V; Burschtin, O; Ayappa, IA; Rapoport, DM
ISSN: 1535-4970
CID: 2590972

Testosterone Deficiency and Sleep Apnea

Burschtin, Omar; Wang, Jing
Obstructive sleep apnea (OSA) is a common condition among middle-aged men and is often associated with reduced testosterone (T) levels. OSA can contribute to fatigue and sexual dysfunction in men. There is suggestion that T supplementation alters ventilatory responses, possibly through effects on central chemoreceptors. Traditionally, it has been recommended that T replacement therapy (TRT) be avoided in the presence of untreated severe sleep apnea. With OSA treatment, however, TRT may not only improve hypogonadism, but may also alleviate erectile/sexual dysfunction.
PMID: 28118875
ISSN: 1556-4088
CID: 2418432

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Abeta42 Levels in Cognitively Normal Elderly

Varga, Andrew W; Wohlleber, Margaret E; Gimenez, Sandra; Romero, Sergio; Alonso, Joan F; Ducca, Emma L; Kam, Korey; Lewis, Clifton; Tanzi, Emily B; Tweardy, Samuel; Kishi, Akifumi; Parekh, Ankit; Fischer, Esther; Gumb, Tyler; Alcolea, Daniel; Fortea, Juan; Lleo, Alberto; Blennow, Kaj; Zetterberg, Henrik; Mosconi, Lisa; Glodzik, Lidia; Pirraglia, Elizabeth; Burschtin, Omar E; de Leon, Mony J; Rapoport, David M; Lu, Shou-En; Ayappa, Indu; Osorio, Ricardo S
STUDY OBJECTIVES: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Abeta). We thus aimed to examine relationships between concentrations of Abeta42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. METHODS: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Abeta42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Abeta42 groups to compare SWS bout length using survival analyses. RESULTS: A significant inverse correlation was found between CSF Abeta42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Abeta42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Abeta42. CONCLUSIONS: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Abeta42, suggesting that disturbed sleep might drive an increase in soluble brain Abeta levels prior to amyloid deposition.
PMID: 27568802
ISSN: 0161-8105
CID: 2310172

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

Varga, Andrew W; Ducca, Emma L; Kishi, Akifumi; Fischer, Esther; Parekh, Ankit; Koushyk, Viachaslau; Yau, Po Lai; Gumb, Tyler; Leibert, David P; Wohlleber, Margaret E; Burschtin, Omar E; Convit, Antonio; Rapoport, David M; Osorio, Ricardo S; Ayappa, Indu
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.
PMID: 27143431
ISSN: 1558-1497
CID: 2100842

Testosterone Deficiency and Sleep Apnea

Burschtin, Omar; Wang, Jing
Obstructive sleep apnea (OSA) is a common condition among middle-aged men and is often associated with reduced testosterone (T) levels. OSA can contribute to fatigue and sexual dysfunction in men. There is suggestion that T supplementation alters ventilatory responses, possibly through effects on central chemoreceptors. Traditionally, it has been recommended that T replacement therapy (TRT) be avoided in the presence of untreated severe sleep apnea. With OSA treatment, however, TRT may not only improve hypogonadism, but may also alleviate erectile/sexual dysfunction.
PMID: 27132581
ISSN: 1558-318x
CID: 2100692

Effects of ApoE genotype on sleep and overnight consolidation of spatial navigational memory [Meeting Abstract]

Shapiro, S D; Ducca, E L; Wohlleber, M E; Gumb, T; Lewis, C; Castillo, B; Burschtin, O E; Rapoport, D M; Ayappa, I; Osorio, R S; Varga, A W
Introduction: The ApoE4 allele is a major risk factor for development of Alzheimer Disease (AD). Symptoms of AD include early deficits in spatial orientation and alterations in sleep. The effects of ApoE4 on sleep architecture and sleep-dependent memory consolidation are less known, particularly at earlier time points before clinical manifestations are apparent. We investigated the effects of ApoE4 allele on sleep architecture and overnight spatial navigational memory consolidation in cognitively normal elderly individuals. Methods: We recruited 29 cognitively normal elderly subjects (age = 67 +/- 9 years) who underwent one night of standard polysomnography. Subjects performed training and 3 timed trials before and after sleep on the same computer-generated 3D spatial maze. Improvement in average completion time after sleep was calculated. A 20-minute psychomotor vigilance test (PVT) was performed in the morning prior to the maze trials. ApoE genotype was determined from serum. Individuals with at least 1 ApoE4 were considered at risk carriers. Results: Of 29 subjects, 17 were control and 12 had at least one ApoE4 allele. Both groups were similar in age, total sleep time, sleep efficiency, sleep architecture, severity of sleep disordered breathing, PVT performance, and pre-sleep baseline maze performance. The control group had significant improvements in maze performance after sleep (390 + 135 sec vs 302 + 121 sec, p < 0.002) while ApoE4 carriers had no significant change in performance (349 + 159 sec vs 358 + 178 sec, p = 0.82). We observed a trend toward a difference in the median of individual changes in overnight performance between groups (28.8% vs-11.8% respectively, p = 0.066). Conclusion: Cognitively normal subjects with at least one ApoE4 allele showed a decreased ability to consolidate spatial navigational memory during sleep. Sleep-dependent spatial memory deficits observed may represent an endophenotype of ApoE4 genotype or may help establish risk for development of subsequent AD
ISSN: 1550-9109
CID: 2153022

CSF Abeta42 levels may increase due to agedependent slow-wave sleep loss priorto amyloid deposition in humans [Meeting Abstract]

Osorio, R S; Wohlleber, M; Gimenez, S; Romero, S; Ducca, E L; Gumb, T; Parekh, A; Varga, A; Burschtin, O; Ayappa, I; Rapoport, D M; De, Leon M
Background: Recently, several studies have provided evidence that Abeta dynamics are influenced by the sleep-wake cycle. In transgenic mice, soluble Abeta levels are higher in the interstitial space during wakefulness and lower during sleep, while sleep deprivation increases Abeta concentrations and accelerates Abeta plaque deposition. In humans, in a study where serial cerebrospinal fluid (CSF) samples were collected for 36 hours, Abeta42 concentrations fluctuated with a diurnal pattern, with the lowest Abeta42 levels in the morning sampling. This CSF Abeta diurnal pattern has been related to higher synaptic activity during wakefulness and decreased synaptic activity during slow wave sleep (SWS). In the elderly, brain soluble Abeta42 levels may be relatively increased as a result of: a) agedependent loss of SWS; and, b) sleep disturbances common in late-life that disrupt SWS. The present study examined whether SWS was associated with CSF Abeta42 levels in a morning lumbar puncture (LP) performed between 11:00 AM-01:00 PM. Methods: In a sample of 22 cognitively normal elderly (age 66.5+/-6.7; range 56-83) with available CSF results, we performed a nocturnal polysomnography (NPSG) (average time interval between the NPSG and the LP 12.9+/-10.1 months, range 0-31). 3 subjects had a CSF P-tau/ Abeta42 ratio suggestive of preclinical AD (based on our own dataset of cognitively normal and AD patients modeled to determine the optimal cut-off for diagnostic prediction of AD) and were excluded. Subjects were further divided by median Abeta42 levels (671.95 pg/mL) into High/Low Abeta42. Results: The percent time spent in SWS (%SWS) and absolute SWA were inversely associated with CSF Abeta42 levels (r=-0.70, p<0.01; r=-0.74, p<0.01). There were no associations with the percent time spent in N1, N2 or REM. Results were also significant after controlling for BMI, age, ApoE4 or after including the preclinical AD subjects in the analysis. In group comparisons, normalized SWA in the first cycle was lower in the 'High' Abeta42 group (C3 p<0.05; F4 p <0.1) (Figure 1). Conclusions: In the absence of AD pathology, reduced %SWS or SWA are associated with increases in CSF Abeta42. (Figure Presented)
ISSN: 1552-5260
CID: 1923912

Effect Of Scoring Rules And Cut-Offs For Apnea-Hypopnea Index (ahi) In Clinical And Research Populations [Meeting Abstract]

Garbuio, S; Burschtin, O; Osorio, RS; Rapoport, DM; Ayappa, IA
ISSN: 1535-4970
CID: 2161772

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

Osorio, Ricardo S; Ayappa, Indu; Mantua, Janna; Gumb, Tyler; Varga, Andrew; Mooney, Anne M; Burschtin, Omar E; Taxin, Zachary; During, Emmanuel; Spector, Nicole; Biagioni, Milton; Pirraglia, Elizabeth; Lau, Hiuyan; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou-En; Mosconi, Lisa; Glodzik, Lidia; Rapoport, David M; de Leon, Mony J
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) Alzheimer's 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 (Abeta-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 Abeta-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 Abeta-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Abeta-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's 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.
PMID: 24439479
ISSN: 0197-4580
CID: 851792