Prader Willi Syndrome and excessive daytime sleepiness

Prader Willi Syndrome (PWS) is a rare genetic disorder characterized by a range of physical, psychological and physiological abnormalities. PWS patients may also demonstrate a range of abnormalities of sleep architecture and of breathing during sleep, and excessive daytime sleepiness (EDS). In the general population EDS is associated with Obstructive Sleep Apnea Syndrome (OSAS). In PWS, by contrast, OSAS is unlikely to fully explain EDS and other factors, including hypothalamic dysfunction are likely to contribute. The present review examines OSAS and hypothalamic dysfunction and other contributing factors to EDS in PWS.     

The origin of excessive daytime sleepiness in the Prader-Willi syndrome

The polygraphically recorded sleep-wake continuum of 21 Prader-Willi syndrome (PWS) patients was compared with that of 19 normal people. In the Prader-Willi group, excessive daytime sleepiness (EDS) is found in 95% of subjects, and rapid eye movement (REM) sleep disorders occur in 52%. These two features were significantly different from the normal group of subjects. No indications were found for the presence of the apnoea syndrome. The REM sleep disorders are: sleep onset rapid eye movements (SOREM), REM sleep in naps, many arousals during REM sleep, and a significant decrease in total REM sleep. These disturbances in the Prader-Willi group, combined with the presence of EDS and sometimes of cataplexy, are likely to be expressions of a narcoleptic syndrome although this was not sustained by the HI-A-DR2 expression above normal. The quality of life of PWS subjects can be improved in some cases by treating them as narcoieptic patients.     

Hypocretin deficiency in Prader–Willi syndrome

Four patients with clinically and genetically confirmed Prader-Willi syndrome (PWS) underwent nocturnal polysomnograpy (PSG), multiple sleep latency test (MSLT), human leukocyte antigens (HLA) typing and estimation of cerebrospinal fluid (CSF) hypocretin-1 (Hcrt-1) level to investigate if a role of hypothalamic dysfunction and sleep disturbance might be functionally connected through the hypocretin (orexin) system. In all four patients physical examination confirmed extreme obesity (increasing with age) with dysmorphogenetic features. Excessive daytime sleepiness (EDS) was manifested in only two subjects without any imperative feature. None of the patients under study suffered from cataplexy. Nocturnal PSG revealed fragmented sleep with low efficiency, the hypopnea and apnea indexes increasing from borderline up to very high values in direct proportion to the patients' age. MSLT latency was shortened in two patients with clinically expressed EDS, only one sleep onset rapid eye movements (REM) period (SOREM) was found. HLA typing showed DQB1*0602 positivity in two patients; the further two were negative. Mean value of CSF Hcrt-1 in the patients group was down to 164 +/- 46.8 pg/ml (in comparison with 265.8 +/- 48.8 pg/ml in 10 young healthy subjects, P=0.02). The deficiency of CSF Hcrt-1 level correlated in PWS patients with their EDS severity.     

Sleep disturbances and behavioural problems in adults with Prader–Willi syndrome

Background Individuals with Prader–Willi syndrome (PWS) are at risk of sleep disturbances, such as excessive daytime sleepiness (EDS) and sleep apnoea, and behavioural problems. Sleep disturbances and their relationship with other variables had not been researched extensively in adults with PWS. Method Sleep disturbances and behavioural problems were investigated in adults with genetically confirmed PWS using standardised questionnaires. Results of adults with paternal deletion (n = 45) were compared with those of adults with maternal uniparental disomy (n = 33). Results Eleven adults with PWS (i.e. 15%) had a current sleep problem, mostly night waking problems. Twenty‐six adults with PWS (i.e. 33%) suffered from severe EDS. No differences in prevalence of sleep disturbances between genetic subtypes were found. Seventeen adults with deletion (i.e. 38%) and 17 adults with maternal uniparental disomy (i.e. 52%) had behavioural problems. No significant relationships were found between sleep disturbances and behavioural problems. Conclusions In adults with PWS, EDS is the most common type of sleep disturbance. Men and individuals with relative high body mass index are at increased risk for EDS. More research, aimed at developing a suitable screening instrument for sleep apnoea in adults with PWS, is necessary. Clinical implications of the findings are discussed.     

Excessive daytime sleepiness and sleep complaints among children with epilepsy

OBJECTIVE: Excessive daytime sleepiness (EDS) and sleep complaints are common among adults with epilepsy. We hypothesized that children with epilepsy have worse daytime sleepiness compared with controls. METHODS: Children with and without epilepsy between ages 8 and 18 were recruited for the study. Parents and children were asked to fill out the Pediatric Sleep Questionnaire (PSQ) and Pediatric Daytime Sleepiness Scale (PDSS), respectively. The Mann-Whitney U test was used for group comparisons, with the Fischer exact or chi2 test for categorical variables. Regression analysis was used to identify predictors of EDS. RESULTS: Twenty-six patients and matched controls were recruited for the study. Parents of children with epilepsy more often reported EDS (P < 0.001), symptoms of sleep-disordered breathing (P < 0.001), and parasomnias (P < 0.001) compared with controls. On the PDSS, children with epilepsy reported worse daytime sleepiness scores compared with controls (15.48 +/- 6.4 vs 11.88 +/- 5.25, P = 0.037). Based on conditional logistic regression modeling, symptoms of excessive daytime sleepiness [corrected] (OR = 15.3, 95% CI = 1.4-166.6) and parasomnias (OR = 12.4, 95% CI = 1.01-151.6) were significantly associated with having epilepsy when adjusted for duration of nightime sleep. Further, 10 children (38.5%) with epilepsy reported positive sleep-disordered breathing, whereas no one in the control group reported SDB (P < 0.001) [corrected] Epilepsy syndrome, anticonvulsants used, and presence or absence of seizure freedom, however, were not significant predictors of EDS among patients. CONCLUSIONS: Daytime sleepiness appears to be common in children with epilepsy, and may be due to underlying sleep disorders. Further confirmatory studies are needed using screening questionnaires and formal sleep studies to systematically study the prevalence of sleep complaints and role of sleep disorders in these patients.     

Daytime sleep in Parkinson's disease measured by episodes of immobility

Excessive daytime sleepiness (EDS) is common in Parkinson's Disease (PD). Actigraphy uses periods of immobility as surrogate markers of nighttime sleep but there are no examples of its use in assessing EDS of PD. A commercial wrist worn system for measuring bradykinesia and dyskinesia also detects 2 min periods of immobility, which have a 85.2% concordance with the detection of sleep by ambulatory daytime polysomnography, (p < 0.0001 Chi Squared). High Epworth Sleepiness Scores (ESS) were associated with a proportion of time immobile (PTI) (p = 0.01 Mann–Whitney U). The median PTI between 0900 and 1800 h w in 30 age matched control subjects was 2%, representing 10 min and PTI at or above the 75th percentile (5% or 27 min) was taken as a high level. PD patients had higher PTI (median 4.8%) than controls (p < 0.0001, Mann–Whitney U). PD subjects with a high PTI had more bradykinesia, less dyskinesia and higher PDQ39 scores than those with low PTI. There was no relationship between PTI and dose or type of PD medications. However, in 53% of subjects, PTI increased in the 30–60 min after levodopa confirming that in some subjects levodopa results in increased sleepiness. In summary, immobility is a surrogate marker of daytime sleep in PD, confirmed by correlation with PSG and ESS. PD subjects measured this way are more likely to be sleepy and sleepy PD subjects are more likely to be bradykinetic and have a higher PDQ39. Levodopa leads to an increase in sleepiness in more than half of subjects post dosing.     

Comment prendre en charge la somnolence associée à la maladie de Parkinson ?

Excessive daytime sleepiness (EDS) is frequent in Parkinson's disease. It should be explored by an Epworth sleepiness scale, a nighttime sleep recording and multiple sleep latency tests. EDS can be secondary to disturbed nighttime sleep that should be explored first. The main reasons for nighttime sleep disturbances are pain, nycturia, restless legs syndrome, obstructive sleep apnea syndrome and depression. They should be treated step by step. EDS can also be secondary to antiparkinsonien dopaminergic treatments that can induce nighttime insomnia and/or daytime sleepiness sometimes with sleep attacks. Treatment modifications and, when indicated, deep brain stimulation can improve these symptoms. Furthermore, EDS can be secondary to the disease itself modifying the sleep wake regulation systems. When the treatment of disturbed nighttime sleep and adjustments of the dopaminergic treatments are not sufficient to improve EDS, wake promoting treatments can be used. Their efficacy is variable but new hopeful drugs are coming soon.     

Excessive daytime sleepiness and sleep benefit in Parkinson's disease: a community-based study.

The objective of this study was to investigate the frequency of excessive daytime sleepiness (EDS) and the beneficial effect of sleep on motor performance in an unselected community-based sample of patients with Parkinson's disease (PD). Furthermore, we wanted to identify possible risk factors to these phenomena. Detailed information on somnolence and sleep during daytime, as well as sleep benefit (SB) on awakening, was collected through a questionnaire among 245 patients with PD. Daytime somnolence was graded in groups of no somnolence, mild daytime sleepiness, and EDS. In addition, the occurrence of somnolence in the patients with PD was compared with the occurrence among control groups of patients with diabetes mellitus and of healthy elderly subjects. The correlations between EDS and SB and various motor- and non-motor symptoms of PD were evaluated. Among the patients with PD, 15.5% experienced EDS, significantly more than in the patients with diabetes mellitus (4%) and the healthy control subjects (1%). The frequency of mild daytime sleepiness was similar (10%) in patients with PD and control subjects. The patients with EDS had significantly higher staging of PD, were more disabled, and showed a higher frequency of cognitive decline compared with the patients without somnolence. They also had been using levodopa for a longer time and had more hallucinations. The occurrence of nocturnal sleeping problems and the use of sleeping pills was similar in the two groups, as was the mean age at examination, duration of PD, and presence of fluctuations and dyskinesias. SB was found in 42.2% of the patients with PD. These patients had been using levodopa for significantly longer and had significantly more fluctuations and dyskinesias compared with the patients without SB. Our results suggest that mild daytime sleepiness may be a result of normal aging, whereas more severe EDS can be explained by the neuropathologic changes of PD. The data from this community-based study confirms the previously reported high frequencies of SB.     

The clinical and laboratory assessment of the sleepy child

Excessive sleepiness is defined as sleepiness that occurs in a situation when an individual would usually be expected to be awake and alert. Hypersomnia is characterized by recurrent episodes of excessive daytime sleepiness (EDS) or prolonged nighttime sleep, which affects the everyday life of the patient. Clinical surveys have reported that EDS is a complaint observed in up to 68% of normal high school children, with a negative impact in academic achievement and extracurricular activity. Clues toward recognizing childhood daytime sleepiness may be sleeping longer hours than expected for age, daytime naps beyond normal for age, being sleepy when other children of the same age are active and alert, and sleeping more than previously. Causes of EDS are arbitrarily divided into 3 categories: insufficient nighttime sleep, fragmented nighttime sleep, and increased drive of sleep. A list of various causes of EDS in children has been discussed. A detailed history along with examination of the upper airway is crucial in evaluating patients with EDS. Appropriate screening tools such as sleep logs, sleepiness scales, and sleep questionnaires further help in identifying and quantifying the degree of sleepiness. Confirmatory tests such as polysomnography, multiple sleep latency test, and actigraphy along with referral to a sleep physician may be necessary in appropriate cases. Details of other ancillary testing such use of cerebrospinal fluid orexin levels, HLA subtyping, and so on have also been provided.     

Increased dopaminergic function in the thalamus is associated with excessive daytime sleepiness

Objectives/BackgroundExcessive daytime sleepiness (EDS) is a common disorder, which can manifest in isolation or in combination with other neurological or psychiatric disorders. We know relatively little about the mechanisms underlying the development of EDS and the clinical management of patients with EDS remains an unmet need. In this study, we hypothesised that thalamic dopaminergic function would be altered in subjects with EDS and we sought to investigate this by assessing [¹²³I]FP-CIT Single Photon Emission Computed Tomography (SPECT) data, which is a molecular imaging marker of dopamine transporter (DAT).Patients/MethodsWe performed a case–control study using people registered as healthy subjects in the Parkinson's Progression Markers Initiative database. We assessed and compared semi-quantified [¹²³I]FP-CIT-SPECT in two groups of 21 healthy subjects with and without EDS, who were matched for age, gender, years of education and Rapid eyemovement (REM) sleep behaviour disorder (RBD) Questionnaire scores.ResultsOur findings show increased thalamic DAT binding in people with EDS compared to matched healthy subjects without EDS. Higher thalamic DAT binding also correlated with worse EDS scores.ConclusionOur findings provide evidence that increased dopaminergic function in the thalamus may mediate excessive daytime sleepiness in humans.     

The effect of short or long sleep duration on quality of life and depression: an internet-based survey in Japan

BackgroundTo date, no previous studies have evaluated the relationship between sleep duration and quality of life (QOL) or depression in the general population after controlling for daytime sleepiness and sleep disturbances.MethodsA web-based cross-sectional survey was conducted with 8698 subjects aged 20–69 years. We examined the relationships between weekday sleep duration and daytime sleepiness, sleep disturbance, QOL and depression, using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (without the item for sleep duration), 8-item Short Form and Center for Epidemiological Studies Depression Scale (CES-D).ResultsDaytime sleepiness tended to increase in proportion to shorter weekday sleep durations. Sleep disturbances, physical and mental QOL, and CES-D scores were worse in both the shorter and longer sleep groups compared with the group with 7–8 h of sleep. Hierarchical logistic regression analyses revealed that short sleep duration but not long sleep duration was significantly associated with reduction of both physical and mental QOL, even after controlling for the presence of daytime sleepiness and sleep disturbance. Both short and long sleep duration were independently and significantly correlated with depression after controlling for daytime sleepiness; however, there was no statistically significant association after adjusting for the effects of sleep disturbance.ConclusionsThe results suggested adverse effects of short sleep but not long sleep on both physical and mental QOL. In addition, the negative impact of specific types of sleep disturbance on depression may be greater than the impact of shortening of sleep duration.     

Prostaglandin D synthase (beta trace) levels in sleep apnea patients with and without sleepiness

BACKGROUND: Excessive daytime sleepiness (EDS) occurs often in patients with obstructive sleep apnea syndrome (OSAS). However, not all patients present EDS. We hypothesized that the prostaglandin D2 system (PGD2) may be involved in the pathogenesis of EDS associated with OSAS. METHODS: We measured the levels of lipocalin-type PGD synthase (L-PGDS), the enzyme that produces PGD2, in the serum of 47 patients with OSAS (26 with and 21 without EDS) and 18 healthy controls. RESULTS: Patients with EDS had higher levels of L-PGDS (0.73+/-0.06 mg/L) than patients without EDS (0.58+/-0.03 mg/L, p<0.05) and controls (0.62+/-0.02 mg/L, p<0.05). L-PGDS levels in patients without EDS and controls were similar. CONCLUSION: The increased levels of circulating L-PGDS detected in OSAS patients with EDS suggest a possible role of the prostaglandin D system in the pathophysiology of daytime sleepiness in these patients.     

Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an overview

Sleep disturbances are frequent in Parkinson disease. These disorders can be broadly categorized into those that involve nocturnal sleep and excessive daytime sleepiness. The disorders that are often observed during the night in PD include sleep fragmentation that may be due to recurrent PD symptoms, sleep apnea, Restless Leg Syndrome/ periodic limb movements and REM sleep behavior disorder. Excessive daytime sleepiness is also a common occurrence in PD. EDS can arise from several etiologies, and patients may have more than one etiology responsible. The causes of EDS include nocturnal sleep disorder with sleep deprivation and resulting daytime somnolence, the effect of drugs used to treat PD, and possibly neurodegeneration of central sleep/wake areas. Appropriate diagnosis of the sleep disturbance affecting a PD patient can lead to specific treatments that can consolidate nocturnal sleep and enhance daytime alertness.     

The impact of obesity and weight gain on development of sleep problems in a population-based sample

ObjectivesThe objective of this study was to investigate the role of obesity and weight gain in the development of sleep problems in a population-based cohort.Material and methodsA population-based sample of men (n = 1896, aged 40–79 years) and women (n = 5116, age ≥20 years) responded to questionnaires at baseline and follow-up after 10–13 years. Sleep problems were assessed through questions about difficulties initiating sleep (DIS), difficulties maintaining sleep (DMS), excessive daytime sleepiness (EDS), and insomnia. Body mass index (BMI) was calculated from self-reported weight and height at both baseline and follow-up, while confounding factors (physical activity, tobacco and alcohol use, somatic disease, and snoring) were based on responses at baseline.ResultsAlthough overweight and obese subjects reported more sleep problems at baseline, there was no independent association between BMI level at baseline and development of new sleep problems. Subjects in the quartile with the highest rise in BMI with a weight gain exceeding 2.06 kg/m² had a higher risk of developing DMS [adjusted odds ratio (OR) 1.58; 95% confidence interval (CI) 1.25–2.01), EDS (2.25; 1.65–3.06], and insomnia (2.78; 1.60–4.82). Weight gain was not associated with the development of DIS.ConclusionsWeight gain is an independent risk factor for developing several sleep problems and daytime sleepiness. The presence of overweight and weight gain should be considered when treating patients with sleep problems.     

Detection of sleep onset by analysis of slow eye movements: a preliminary study of MSLT recordings

BackgroundExcessive daytime sleepiness (EDS) adversely impacts daily activity and quality of life. Evaluation of EDS should be as easy and effective as possible. Multiple sleep latency test (MSLT) represents the standard in EDS evaluation. It is, however, a long and expensive test. Slow eye movements (SEMs) occurring at the wake–sleep transition could be an easy and reliable marker of sleepiness. We have developed an automatic method for the detection of SEMs. In the present preliminary work we compare standard measurement of EDS with visual and automatic detection of SEMs, both performed on MSLT recordings.MethodsWe compared sleep latency, obtained upon standard analysis of MSLT with visually and automatically detected SEM latency, in MSLT tests performed in a population of 20 subjects, (10 Obstructive Sleep Apnea Syndrome (OSAS) patients and 10 patients with normal MSLT).ResultsThere were no significant differences between SEMs latency and standard determined sleep latency both in OSAS and normal MSLT patients. Automatic and visual analysis of SEMs gave comparable results. Both SEMs latency and sleep latency were significantly shorter in OSAS patients than normal MSLT patients.ConclusionSEMs can be easily detected automatically and represent an effective marker of sleepiness in those conditions usually characterised by sleep onset with NREM sleep. Their performance equals that of standard measurements of sleep onset in MSLT recordings at least for OSAS and normal MSLT patients. Our study is, however, still preliminary and needs confirmation on a larger number of patients and in other clinical conditions characterised by EDS.     

Risk factors for excessive sleepiness in older adults

OBJECTIVE: To determine risk factors for excessive daytime sleepiness in older adults. METHODS: This is a cross-sectional study assessing multiple risk factors for excessive daytime sleepiness in older subjects (mean age, 78 years; range 65-98 years) with (n=149) and without (n=144) complaints of frequent excessive daytime sleepiness. Assessment of risk factors included full in-laboratory sleep studies. RESULTS: Excessive sleepiness among the elderly is multifactorial. Multivariable modeling identified the following as simultaneously significant risk factors for excessive sleepiness: severe sleep-disordered breathing (apnea-hypopnea index, >30 episodes/hr), self-report of poor sleep quality, increased percentage of time in rapid eye movement sleep, pain at night at least three times per week, wheezing or whistling from chest at night, and medications with sleepiness as a side effect. Male sex also was associated with increased risk, whereas alcohol use (more than seven beverages per week) reduced the risk for sleepiness. Multiple risk factors were more commonly present in those with complaints of sleepiness. The presence of periodic limb movements, which are common in older adults, was not associated with sleepiness. INTERPRETATION: There is a distinct differential diagnosis of excessive daytime sleepiness in older adults. Many of the risk factors that we identified are treatable.     

Lack of association between MAOA-uVNTR variants and excessive daytime sleepiness

Sleep disorders are highly prevalent in the population and have dramatic health, social, and economic impacts. However, their treatments may remain symptomatic due to ignorance of molecular factors which may provide fundamental insights into the neurological bases of sleep. Excessive daytime sleepiness (EDS) is a common complaint encountered in neurological practice with significant effects both on individuals and on society. We aimed to investigate the role of monoamine oxidase A (MAOA) as a candidate gene in EDS. Epworth sleepiness scale (ESS) was applied to 221 subjects who were also genotyped for MAOA upstream variable number of tandem repeats (MAOA-uVNTR). Patient group displayed higher ESS values (mean 12.67) when compared with the control group (mean 6.38). However, MAOA-uVNTR genotypes did not show a significant association with ESS scores neither on women nor on men. Finally, these data suggest further replications in different populations. Moreover, the investigation of some other genes together with MAOA and/or some possible regulatory molecular mechanisms may offer a more comprehensive approach in the role of genetic factors contributing to EDS.     

Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects.

Excessive daytime sleepiness is a complaint characterizing many disorders of the wakefulness--sleep cycle. This paper addresses the complaint of sleepiness objectively by an attempt to differentiate a group of control subjects from a group of patients with unambiguous narcolepsy. Fourteen control and 27 narcoleptic subjects were evaluated by one of three protocols involving nocturnal recordings, detailed interviews, and 5 or more 20-min opportunities to sleep offered at 2-h intervals beginning at 10.00 o'clock, +/- 30 min. Each 20-min opportunity to sleep was given to subjects lying in a darkened quiet room and asked to try to fall asleep. Polysomnographic variables were monitored and sleep was scored in 30-sec epochs by standard criteria. The interval from the start of each test to the first epoch of NREM (including stage 1 sleep) or REM sleep was called sleep latency. In two of the protocols, the subjects were awakened immediately after sleep onset. In the third protocol, the subjects were awakened after 10 min of sleep. Narcoleptics consistently fell asleep much more readily than did control subjects. We conclude that the Multiple Sleep latency test, in addition to providing opportunities to clinically document sleep onset REM sleep periods, can demonstrate pathological sleepiness. Based on these data, we suggest that an average sleep latency less than 5 min be set as the minimum cutoff point for pathological sleepiness.     

Quality of sleep in primary focal dystonia: a case–control study

Background: Sleep disturbances are common in patients with movement disorders. Evaluating quality of sleep is of primary importance because of the effect that nocturnal and daytime sleep abnormalities exert on general health status. However, quality of sleep has never been addressed in detail in patients with dystonia. The aim of this case–control study was to analyse quality of sleep in patients with the two most common forms of primary focal dystonia, blepharospasm (BSP) and cervical dystonia (CD). Methods: We evaluated quality of sleep (Pittsburgh Sleep Quality Index, PSQI) and excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) in 98 patients with focal adult‐onset dystonia (52 with BSP; 46 with CD) and in a group of 56 age‐and gender‐matched healthy subjects. The Beck Depression Inventory (BDI) was used for the evaluation of depressive symptomatology. Results: Quality of sleep was impaired (significantly higher PSQI scores) in both groups of patients. However, differences in PSQI scores between patients with CD and control subjects were partly confounded by BDI scores, whereas differences in PSQI scores between patients with BSP and control subjects were not influenced by BDI. Excessive daytime sleepiness was not significantly more frequent than in control subjects in either patients with BSP or patients with CD. Conclusions: This study suggests that the assessment and treatment of insomnia‐related complaints should be considered in global management plans of patients with focal dystonia, particularly in those affected by BSP.     

Sleep characteristics associated with drowsy driving

ObjectiveThe aim of this study was to evaluate sleep characteristics associated with drowsy driving in an adult population.MethodsThe study subjects consisted of 1675 adults aged 19 years or older who completed a population-based questionnaire survey on sleep habits. Experiences of drowsy driving were obtained from self-reported data. We investigated sleep-related variables including sleep duration, sleep efficiency, chronotype, subjective sleep perception, daytime sleepiness, sleep quality, and snoring. We performed multivariate logistic regression analysis to determine sleep characteristics independently associated with drowsy driving.ResultsThe mean age of the subjects was 43.2 years, and 66.3% were men. The prevalence of self-reported drowsy driving was 23.6% (396 of 1675), and 33.1% of subjects experienced dozing at the wheel at least once a month. Multivariate analysis demonstrated that men, office and manual workers, excessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were independently associated with drowsy driving. Subgroup analyses revealed that reduced weekday sleep duration was a risk factor of drowsy driving in adults with perceived sufficient sleep. On the other hand, frequent alcohol drinking significantly increased risk of drowsy driving in the subgroup with perceived sleep insufficiency. Furthermore, ordinal regression analyses confirmed the association between sleep characteristics and drowsy driving across different drowsy driving frequencies.ConclusionExcessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were sleep-related risk factors for drowsy driving. In addition to maintaining healthy sleep habits, individuals at high risk should be encouraged to evaluate underlying sleep disorders or psychiatric problems to prevent drowsy driving.