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Reply to: Ventilatory Burden in Obstructive Sleep Apnea: A Novel Indicator for Assessing Severity?

Parekh, Ankit; Kam, Korey; Wickramaratne, Sajila; Tolbert, Thomas M; Varga, Andrew W; Osorio, Ricardo S; Andersen, Monica L; de Godoy, Luciana B M; Palombini, Luciana O; Tufik, Sergio; Ayappa, Indu; Rapoport, David M
PMID: 38271706
ISSN: 1535-4970
CID: 5625252

Ventilatory Burden as a Measure of Obstructive Sleep Apnea Severity Is Predictive of Cardiovascular and All-Cause Mortality

Parekh, Ankit; Kam, Korey; Wickramaratne, Sajila; Tolbert, Thomas M; Varga, Andrew; Osorio, Ricardo; Andersen, Monica; de Godoy, Luciana B M; Palombini, Luciana O; Tufik, Sergio; Ayappa, Indu; Rapoport, David M
PMID: 37698405
ISSN: 1535-4970
CID: 5594042

Night-to-night reliability and agreement of obstructive sleep apnea pathophysiologic mechanisms estimated with phenotyping using polysomnography in cognitively normal elderly participants

Tolbert, Thomas M; Schoenholz, Reagan L; Parekh, Ankit; Berkalieva, Asem; Osorio, Ricardo S; Ayappa, Indu; Rapoport, David M
STUDY OBJECTIVES:Phenotyping using polysomnography (PUP) is an algorithmic method to quantify physiologic mechanisms underlying obstructive sleep apnea (OSA): loop gain (LG1), arousal threshold (ArTH), and upper airway collapsibility (Vpassive) and muscular compensation (Vcomp). The consecutive-night test-retest reliability and agreement of PUP-derived estimates are unknown. From a cohort of elderly (age ≥55 years), largely non-sleepy, community-dwelling volunteers who underwent in-lab polysomnography (PSG) on 2 consecutive nights, we determined the test-retest reliability and agreement of PUP-estimated physiologic factors. METHODS:Participants who had an apnea-hypopnea index (AHI3A) of at least 15 events per hour on the first night were included. PUP analyses were performed on each of the two PSGs from each participant. Physiologic factor estimates were derived from NREM sleep and compared across nights using intraclass correlation coefficients for reliability and smallest real differences (SRD) for agreement. RESULTS:Two PSGs from each of 43 participants (86 total) were analyzed. A first-night effect was evident with increased sleep time and stability and decreased OSA severity on the second night. LG1, ArTH, and Vpassive demonstrated good reliability (ICC > 0.80). Vcomp had modest reliability (ICC = 0.67). For all physiologic factors, SRD values were approximately 20% or more of the observed ranges, suggesting limited agreement of longitudinal measurements for a given individual. CONCLUSIONS:For NREM sleep in cognitively normal elderly individuals with OSA, PUP-estimated LG1, ArTH, and Vpassive demonstrated consistent relative ranking of individuals (good reliability) on short-term repeat measurement. For all physiologic factors, longitudinal measurements demonstrated substantial intraindividual variability across nights (limited agreement).
PMID: 36881682
ISSN: 1550-9109
CID: 5594882

Editorial: Additive or synergistic impacts of sleep, circadian rhythm disturbances and other modifiable risk factors on established and novel plasma biomarkers of Alzheimer's disease pathology

Bubu, Omonigho M.; Kam, Korey; Parekh, Ankit; Ayappa, Indu
SCOPUS:85150984310
ISSN: 1663-4365
CID: 5460032

Acute OSA Impacts Diurnal Alzheimer's Biomarkers Through Nocturnal Hypoxemia and State Transitions

Kam, Korey; Jun, Jonathan; Parekh, Ankit; Bubu, Omonigho M; Mullins, Anna E; Gu, Chenjuan; Pham, Luu; Wisniewski, Thomas M; Rapoport, David M; Ayappa, Indu; Osorio, Ricardo S; Varga, Andrew W
PMID: 35696622
ISSN: 1535-4970
CID: 5282532

Obstructive Sleep Apnea and Hypertension with Longitudinal β-Amyloid Burden and Cognitive Changes

Bubu, Omonigho M; Kaur, Sonya S; Mbah, Alfred K; Umasabor-Bubu, Ogie Q; Ramos-Cejudo, Jaime; Debure, Ludovic; Mullins, Anna E; Parekh, Ankit; Kam, Korey; Osakwe, Zainab T; Williams, Ellita T; Turner, Arlener D; Glodzik, Lidia; Rapoport, David M; Ogedegbe, Gbenga; Fieremans, Els; de Leon, Mony J; Ayappa, Indu; Jean-Louis, Girardin; Masurkar, Arjun V; Varga, Andrew W; Osorio, Ricardo S
PMID: 35550019
ISSN: 1535-4970
CID: 5213082

The Link between Obstructive Sleep Apnea and Neurocognitive Impairment: An Official American Thoracic Society Workshop Report

Lal, Chitra; Ayappa, Indu; Ayas, Najib; Beaudin, Andrew E; Hoyos, Camilla; Kushida, Clete A; Kaminska, Marta; Mullins, Anna; Naismith, Sharon L; Osorio, Ricardo S; Phillips, Craig L; Parekh, Ankit; Stone, Katie L; Turner, Arlener D; Varga, Andrew W
There is emerging evidence that obstructive sleep apnea (OSA) is a risk factor for preclinical Alzheimer's disease (AD). An American Thoracic Society workshop was convened that included clinicians, basic scientists, and epidemiologists with expertise in OSA, cognition, and dementia, with the overall objectives of summarizing the state of knowledge in the field, identifying important research gaps, and identifying potential directions for future research. Although currently available cognitive screening tests may allow for identification of cognitive impairment in patients with OSA, they should be interpreted with caution. Neuroimaging in OSA can provide surrogate measures of disease chronicity, but it has methodological limitations. Most data on the impact of OSA treatment on cognition are for continuous positive airway pressure (CPAP), with limited data for other treatments. The cognitive domains improving with CPAP show considerable heterogeneity across studies. OSA can negatively influence risk, manifestations, and possibly progression of AD and other forms of dementia. Sleep-dependent memory tasks need greater incorporation into OSA testing, with better delineation of sleep fragmentation versus intermittent hypoxia effects. Plasma biomarkers may prove to be sensitive, feasible, and scalable biomarkers for use in clinical trials. There is strong biological plausibility, but insufficient data, to prove bidirectional causality of the associations between OSA and aging pathology. Engaging, recruiting, and retaining diverse populations in health care and research may help to decrease racial and ethnic disparities in OSA and AD. Key recommendations from the workshop include research aimed at underlying mechanisms; longer-term longitudinal studies with objective assessment of OSA, sensitive cognitive markers, and sleep-dependent cognitive tasks; and pragmatic study designs for interventional studies that control for other factors that may impact cognitive outcomes and use novel biomarkers.
PMCID:9353960
PMID: 35913462
ISSN: 2325-6621
CID: 5312202

Association between lower body temperature and increased tau pathology in cognitively normal older adults

Blessing, Esther M; Parekh, Ankit; Betensky, Rebecca A; Babb, James; Saba, Natalie; Debure, Ludovic; Varga, Andrew W; Ayappa, Indu; Rapoport, David M; Butler, Tracy A; de Leon, Mony J; Wisniewski, Thomas; Lopresti, Brian J; Osorio, Ricardo S
BACKGROUND:Preclinical studies suggest body temperature (Tb) and consequently brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD). Tau phosphorylation is substantially increased by small (<1 °C) decreases in temperature within the human physiological range, and thermoregulatory nuclei are affected by tau pathology early in the AD continuum. In this study we evaluated whether Tb (as a proxy for brain temperature) is cross-sectionally associated with clinically utilized markers of tau pathology in cognitively normal older adults. METHODS:Tb was continuously measured with ingestible telemetry sensors for 48-h. This period also included two nights of nocturnal polysomnography to delineate whether Tb during waking vs sleep is differentially associated with tau pathology. Tau phosphorylation was assessed with plasma and cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (P-tau), sampled the day following Tb measurement. In addition, neurofibrillary tangle (NFT) burden in early Braak stage regions was imaged with PET-MR using the [18F]MK-6240 radiotracer on average one month later. RESULTS:Lower Tb was associated with increased NFT burden, as well as increased plasma and CSF P-tau levels (p < 0.05). NFT burden was associated with lower Tb during waking (p < 0.05) but not during sleep intervals. Plasma and CSF Ptau levels were highly correlated with each other (p < 0.05), and both variables were correlated with tau tangle radiotracer uptake (p < 0.05). CONCLUSIONS:These results, the first available for human, suggest that lower Tb in older adults may be associated with increased soluble and aggregated tau pathology. Our findings add to the substantial preclinical literature associating lower body and brain temperature with tau hyperphosphorylation. CLINICAL TRIAL NUMBER/BACKGROUND:NCT03053908.
PMID: 35550158
ISSN: 1095-953x
CID: 5214682

Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing

Parekh, Ankit; Tolbert, Thomas M; Mooney, Anne M; Ramos-Cejudo, Jaime; Osorio, Ricardo S; Treml, Marcel; Herkenrath, Simon-Dominik; Randerath, Winfried J; Ayappa, Indu; Rapoport, David M
PMID: 34449303
ISSN: 1535-4970
CID: 5147022

Altered K-complex morphology during sustained inspiratory airflow limitation is associated with next-day lapses in vigilance in obstructive sleep apnea

Parekh, Ankit; Kam, Korey; Mullins, Anna E; Castillo, Bresne; Berkalieva, Asem; Mazumdar, Madhu; Varga, Andrew W; Eckert, Danny J; Rapoport, David M; Ayappa, Indu
STUDY OBJECTIVES/OBJECTIVE:Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. METHODS:Data from thirty subjects with moderate-to-severe OSA who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4cmH20 below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every two hours. Changes in proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. RESULTS:Suboptimal CPAP induced SIFL (14.7(20.9) vs. 2.9(9.2); %total sleep time, p<0.001) with a small increase in apnea hypopnea index (AHI3A: 6.5(7.7) vs. 1.9(2.3); p<0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97±0.7 vs. 0.65±0.5, #/min, mean±SD, p<0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. EEG changes were not associated with objective sleepiness. CONCLUSIONS:Sustained inspiratory airflow limitation is associated with altered K-complex morphology including increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with non-visible sleep fragmentation and contribute to increased lapses in vigilance.
PMID: 33433607
ISSN: 1550-9109
CID: 4746682