Bio


I am a physician scientist in the field of sleep medicine in aging and brain function. Using combined polysomnogram and novel neuroimaging technology, I aim to identify potential sleep biomarkers to investigate the mechanism of progression from normal aging to Mild Cognitive Impairment (MCI) or dementia. I also investigate the impact of sleep on cognitive/affective function or behavior abnormality in various neurodevelopmental and neurodegenerative disorders.

Clinical Focus


  • Sleep Medicine

Professional Education


  • Fellowship: Baylor College of Medicine (2006) TX
  • Residency: Baylor College of Medicine (2005) TX
  • Fellowship: Stanford University Sleep Medicine Fellowship (2014) CA
  • Board Certification: American Board of Psychiatry and Neurology, Epilepsy (2013)
  • Board Certification: American Board of Psychiatry and Neurology, Clinical Neurophysiology (2009)
  • Board Certification: American Board of Psychiatry and Neurology, Neurology (2007)
  • Board Certification: American Board of Psychiatry and Neurology, Sleep Medicine (2007)
  • Internship: St. Luke's-Roosevelt Hospital Center (2002) NY
  • Medical Education: Kyoto University, Faculty of Medicine (1997) Japan

Stanford Advisees


All Publications


  • The 5-HTTLPR Long, not Short, Allele Predicts Two-year Longitudinal Increases in Cortisol and Declines in Verbal Memory in Older Adults. International journal of geriatric psychiatry Hirst, R. B., Jordan, J. T., Miryam Schussler-Fiorenza Rose, S., Schneider, L., Kawai, M., Gould, C., Anker, L., Chick, C. F., Beaudreau, S., Hallmayer, J., O'Hara, R. 2020

    Abstract

    OBJECTIVES: The short form or s-allele variant of the serotonin transporter polymorphism (5-HTTLPR), as compared with the long form or l-allele variant, has been associated with the presence of cognitive dysfunction, and particularly memory impairment in older adults. This body of cross-sectional work has culminated in the hypothesis that presence of the s-allele predicts greater memory decline in older adults (1). Yet, to date, there are no longitudinal studies which have investigated this issue.METHODS/DESIGN: Here we examine 109 community-dwelling older adults (mean and SD of age=70.7±8.7years) who underwent blood draw for genotyping, cognitive, and psychological testing at baseline, 12-month, and 24-month follow-up.RESULTS: Multilevel modeling found that s-allele carriers (ss or ls) performed worse than ll homozygotes at baseline on delayed verbal recall. Yet, s-allele carriers' memory performance was stable over the two-year follow-up period, while l-allele homozygotes experienced significant memory decline. l-allele homozygote status was associated with both increased cortisol and decreased memory over time, resulting in attenuated verbal memory performance differences compared to s-allele carriers with age.CONCLUSIONS: Overall, our findings do not support the hypothesis that presence of the 5-HTTLPR s-allele is a marker for memory decline in older adults. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/gps.5319

    View details for PubMedID 32400901

  • Subjective but Not Objective Sleep is Associated with Subsyndromal Anxiety and Depression in Community-Dwelling Older Adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Gould, C. E., Karna, R., Jordan, J., Kawai, M., Hirst, R., Hantke, N., Pirog, S., Cotto, I., Schussler-Fiorenza Rose, S. M., Beaudreau, S. A., O'Hara, R. 2018

    Abstract

    OBJECTIVE: To examine the relationship between subclinical anxiety and depressive symptoms and objective sleep architecture measures and subjective sleep reports in older adults.METHODS: Community-dwelling older adults (N=167) self-rated their current severity of anxiety symptoms, depressive symptoms, daytime sleepiness, and global sleep quality. Participants received overnight ambulatory polysomnography to assess sleep architecture. Multivariate linear regression models examined associations between anxiety and depressive symptoms and objective and subjective sleep measures.RESULTS: Significant findings emerged for subjective sleep, with higher depression and anxiety scores associated with worse global sleep quality and greater anxiety scores associated with greater daytime sleepiness. No significant associations were observed between subclinical levels of anxiety or depressive symptoms with sleep architecture.CONCLUSION: Subclinical levels of late-life anxiety and depression have distinct associations with subjective sleep disturbance. Findings implicate subjective measures of sleep quality and daytime sleepiness as stronger trait markers for subthreshold psychiatric symptoms than objective sleep biomarkers.

    View details for PubMedID 29709510

  • Subjective, but Not Objective Sleep is Associated with Subsyndromal Anxiety and Depression in Community-Dwelling Older Adults The American Journal of Geriatric Psychiatry Gould, C. E., Karna, R., Jordan, J., Kawai, M., Hirst, R., Hantke, N., Pirog, S., Cotto, I., Rose, S., Beaudreau, S. A., O'Hara, R. 2018
  • Association of Anxiety Symptom Clusters with Sleep Quality and Daytime Sleepiness. journals of gerontology. Series B, Psychological sciences and social sciences Gould, C. E., Spira, A. P., Liou-Johnson, V., Cassidy-Eagle, E., Kawai, M., Mashal, N., O'Hara, R., Beaudreau, S. A. 2017

    Abstract

    To better understand links between anxiety and sleep disturbances in older adults, we examined the association of different phenotypic presentations of anxiety (i.e., affective, cognitive, and somatic clusters) with global sleep quality and daytime sleepiness.109 community-dwelling adults aged 66-92 years old (57% female) completed assessments of global sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness Scale), affective anxiety symptoms (Geriatric Anxiety Scale (GAS) affective subscale), cognitive anxiety symptoms (GAS cognitive subscale), and somatic anxiety symptoms (GAS somatic subscale).In hierarchical regression models adjusted for depressive symptoms and health status, greater affective and somatic anxiety were associated with poorer global sleep quality (affective B = 0.30, p = .01; somatic B = 0.41, p = .01). Somatic and cognitive anxiety were associated with greater daytime sleepiness (somatic B = 0.74, p < .001; cognitive B = 0.30, p = .03), but these associations were attenuated by covariates added to the models.These findings indicate that anxiety symptom clusters are differentially associated with specific sleep-related disturbances, underscoring the complex relationship of late-life anxiety to sleep. Results suggest that personalized treatments, such as targeted sleep interventions, may improve specific anxiety-symptom domains, or vice versa.

    View details for DOI 10.1093/geronb/gbx020

    View details for PubMedID 28379498

  • Longitudinal association of delta activity at sleep onset with cognitive and affective function in community-dwelling older adults. International journal of geriatric psychiatry Kawai, M., Beaudreau, S. A., Gould, C. E., Hantke, N. C., Cotto, I., Jordan, J. T., Hirst, R. B., O'Hara, R. 2016; 31 (10): 1124-1135

    Abstract

    This investigation sought to determine whether delta activity at sleep onset (DASO) in the sleep electroencephalography of older adults represents normal variation or is associated with clinical pathology. To this end, we examined its longitudinal associations with cognitive and affective function in older adults without dementia.Participants were 153 community-dwelling older adults without dementia. We evaluated polysomnography (PSG), cognitive performance, and affective function at four time points: baseline, 12, 24, and 36 months. All participants completed PSG and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, visuospatial ability, and measures of anxiety and depression. DASO was defined as sequences of rhythmic anterior delta activity on PSG in the transition from awake to sleep during the baseline assessment (Figure ).At the baseline, 83 women and 70 men, mean age 71.3 ± 0.6 years participated and 19.6% of participants exhibited DASO. Age, years of education, gender, and body mass index did not differ according to DASO status. Linear mixed modeling showed that the presence of DASO was actually associated with lower levels of anxiety and depression. Further, participants with DASO, versus those without DASO, exhibited a trend towards better cognitive performance over time, although none of these associations reached statistical significance.Whereas DASO was associated with better affective function, no significant association was found between DASO and cognitive change over time. These longitudinal findings support the view that the presence of DASO in healthy older adults represents normal variation rather than pathological aging. Copyright © 2016 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/gps.4554

    View details for PubMedID 27554208

  • Tonsillectomy for adult obstructive sleep apnea: A systematic review and meta-analysis. Laryngoscope Camacho, M., Li, D., Kawai, M., Zaghi, S., Teixeira, J., Senchak, A. J., Brietzke, S. E., Frasier, S., Certal, V. 2016; 126 (9): 2176-2186

    Abstract

    To determine if sleepiness and sleep study variables (e.g., Apnea-Hypopnea Index [AHI] and lowest oxygen saturation) improve following isolated tonsillectomy for adult obstructive sleep apnea (OSA).Systematic review and meta-analysis.Nine databases (PubMed/MEDLINE included) were searched through November 24, 2015.Seventeen studies (n = 216 patients, 34.4 ± 10.0 years and body mass index: 29.0 ± 6.1 kg/m(2) ) met criteria. Tonsils sizes were hypertrophied, large, enlarged, extremely enlarged, or grades 2 to 4. Apnea-Hypopnea Index decreased by 65.2% (from 40.5 ± 28.9/hour to 14.1 ± 17.1/hour) (n = 203). The AHI mean difference (MD) was -30.2 per hour (95% confidence interval [CI] -39.3, -21.1) (P value < 0.00001). The AHI SMD was -1.37 (-1.65, -1.09) (large effect). Lowest oxygen saturation improved from 77.7 ± 11.9% to 85.5 ± 8.2% (n = 186). Lowest oxygen saturation MD was 8.5% (95% CI 5.2, 11.8) (P value < 0.00001). The Epworth Sleepiness Scale decreased from 11.6 ± 3.7 to 6.1 ± 3.9 (P value < 0.00001) (n = 125). Individual patient outcomes (n = 54) demonstrated an 85.2% success rate (AHI < 20/hour and ≥ 50% reduction) and a 57.4% cure rate. Individual patient data meta-analysis showed preoperative AHI < 30 per hour to be a significant predictor of surgical success (P value < 0.001) and cure (P value = 0.043); among patients with preoperative AHI < 30 per hour, tonsillectomy success rate was 100% (25 of 25) and cure rate was 84% (21 of 25) with a mean postoperative AHI of 2.4 ± 2.1 per hour; this compares to tonsillectomy success rate of 72.4% (21 of 29), cure rate of 10 of 29 (34.4%), and mean postoperative AHI of 14.3 ± 13.9 per hour for patients with preoperative AHI ≥ 30 per hour.Isolated tonsillectomy can be successful as treatment for adult OSA, especially among patients with large tonsils and mild to moderate OSA (AHI < 30/hour). Laryngoscope, 2016 Laryngoscope, 126:2176-2186, 2016.

    View details for DOI 10.1002/lary.25931

    View details for PubMedID 27005314

  • Delta Activity at Sleep Onset and Cognitive Performance in Community-Dwelling Older Adults SLEEP Kawai, M., Beaudreau, S. A., Gould, C. E., Hantke, N. C., Jordan, J. T., O'Hara, R. 2016; 39 (4): 907-914

    Abstract

    Frontal intermittent rhythmic delta activity (FIRDA) has long been considered to be an abnormal variant in the electroencephalogram (EEG) among older adults. Prior work also indicates a predominance of slow wave EEG activity among patients with dementia. However, instability of state control occurring with aging generally and among many neurodegenerative diseases raises the possibility that FIRDA might represent the intrusion of sleep related elements of the EEG into the waking state. We examined delta activity at sleep onset (DASO) in community-dwelling, older adults without dementia, and examined whether this activity is related to poorer cognitive performance.153 community-dwelling, older adults without dementia underwent overnight polysomnography and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, and visuospatial ability. Delta activity during sleep/wake transitions (scored either as Waking or N1) was analyzed visually.Participants were 83 women and 70 men, mean age 71.3 ± 0.6 y. DASO was present in 30 participants (19.6%). Age, years of education, sex, and body mass index did not differ between DASO (+) and (-) groups. Multiple regression analyses indicated faster reading of the Stroop color words in DASO (+) subjects (P = 0.007). None of the other cognitive domains differed between the two groups.DASO was relatively common in our sample of community-dwelling, older adults without dementia. DASO was not associated with poorer performance on any cognitive domain. Instead, individuals with DASO demonstrated better performance on a simple reading task. Although these findings suggest that an abnormal EEG activity may represent normal variation, our work underscores the importance of distinguishing DASO from FIRDA when examining sleep in older adults.A commentary on this article appears in this issue on page 725.

    View details for DOI 10.5665/sleep.5652

    View details for Web of Science ID 000373186900022

    View details for PubMedCentralID PMC4791624

  • Five-Minute Awake Snoring Test for Determining CPAP Pressures (Five-Minute CPAP Test): A Pilot Study. Sleep disorders Camacho, M., Ruoff, C. M., Kawai, M., Modi, R., Arbee, J., Hekmat, A., Robertson, M., Zaghi, S., Certal, V., Capasso, R., Kushida, C. A. 2016; 2016: 7380874-?

    Abstract

    Objective. To develop a quick, simple, bedside test for determining continuous positive airway pressures (CPAP) for obstructive sleep apnea (OSA) patients. Study Design. Prospective case series at a tertiary medical center. Methods. The Five-Minute Awake Snoring Test for Determining CPAP (Five-Minute CPAP Test) was developed and tested. Patients wear a soft-gel nasal triangle mask while holding a tongue depressor with the wide section (1.75 cm) between the teeth. Fixed pressure nasal CPAP is applied while the patient simulates snoring at 4 centimeters of water pressure. The pressure is incrementally titrated up and then down to determine the lowest pressure at which the patient cannot snore (Quiet Pressure). Results. Overall, thirty-eight patients participated. All could simulate snoring. Correlation coefficients were statistically significant between Quiet Pressures and body mass index (r s = 0.60 [strong positive relationship], p = 0.0088), apnea-hypopnea index (r s = 0.49 [moderate positive relationship], p = 0.039), lowest oxygen saturation (r s = -0.47 [moderate negative relationship], p = 0.048), and oxygen desaturation index (r s = 0.62 [strong positive relationship], p = 0.0057). Conclusion. This pilot study introduces a new concept, which is the final product of over one year of exploration, development, and testing. Five-Minute CPAP Test is a quick, inexpensive, and safe bedside test based on supine awake simulated snoring with nasal CPAP.

    View details for DOI 10.1155/2016/7380874

    View details for PubMedID 26881088

  • Five-Minute Awake Snoring Test for Determining CPAP Pressures (Five-Minute CPAP Test): A Pilot Study Sleep Disorders Camacho, M., Ruoff, C. M., Kawai, M., Modi, R., Arbee, J., Hekmat, A., Robertson, M., Zaghi, S., Certal, V., Capasso, R., Kushida, C. A. 2016; 2016: 8

    View details for DOI 10.1155/2016/7380874

  • Delta Activity at Sleep Onset and Cognitive Performance in Community-Dwelling Older Adults. Sleep Kawai, M., Beaudreau, S. A., Gould, C. E., Hantke, N. C., Jordan, J. T., O'Hara, R. 2016; 39 (4): 907-914

    Abstract

    Frontal intermittent rhythmic delta activity (FIRDA) has long been considered to be an abnormal variant in the electroencephalogram (EEG) among older adults. Prior work also indicates a predominance of slow wave EEG activity among patients with dementia. However, instability of state control occurring with aging generally and among many neurodegenerative diseases raises the possibility that FIRDA might represent the intrusion of sleep related elements of the EEG into the waking state. We examined delta activity at sleep onset (DASO) in community-dwelling, older adults without dementia, and examined whether this activity is related to poorer cognitive performance.153 community-dwelling, older adults without dementia underwent overnight polysomnography and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, and visuospatial ability. Delta activity during sleep/wake transitions (scored either as Waking or N1) was analyzed visually.Participants were 83 women and 70 men, mean age 71.3 ± 0.6 y. DASO was present in 30 participants (19.6%). Age, years of education, sex, and body mass index did not differ between DASO (+) and (-) groups. Multiple regression analyses indicated faster reading of the Stroop color words in DASO (+) subjects (P = 0.007). None of the other cognitive domains differed between the two groups.DASO was relatively common in our sample of community-dwelling, older adults without dementia. DASO was not associated with poorer performance on any cognitive domain. Instead, individuals with DASO demonstrated better performance on a simple reading task. Although these findings suggest that an abnormal EEG activity may represent normal variation, our work underscores the importance of distinguishing DASO from FIRDA when examining sleep in older adults.A commentary on this article appears in this issue on page 725.

    View details for DOI 10.5665/sleep.5652

    View details for PubMedID 26943464

    View details for PubMedCentralID PMC4791624

  • Narcolepsy in African Americans SLEEP Kawai, M., O'Hara, R., Einen, M., Lin, L., Mignot, E. 2015; 38 (11): 1673-1681

    Abstract

    Although narcolepsy affects 0.02-0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States.Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level.182 African-Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy.Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (≤ 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%).Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy.

    View details for DOI 10.5665/sleep.5140

    View details for Web of Science ID 000363740100006

    View details for PubMedCentralID PMC4813366

  • Narcolepsy in African Americans. Sleep Kawai, M., O'Hara, R., Einen, M., Lin, L., Mignot, E. 2015; 38 (11): 1673-81

    Abstract

    Although narcolepsy affects 0.02-0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States.Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level.182 African-Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy.Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (≤ 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%).Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy.

    View details for DOI 10.5665/sleep.5140

    View details for PubMedID 26158891

    View details for PubMedCentralID PMC4813366