How Sleep Problems and Stroke Are Connected: Causes, Health Effects, and Treatment Approaches

Elevated daytime maximum ABP is strongly associated with increased stroke risk, particularly in individuals with heightened arterial stiffness. Subjects in the highest quartile of daytime maximum BP exhibit a significantly greater incidence of stroke compared to those in lower quartiles [16]. In older adults, ABP monitoring provides more reliable stroke risk prediction than office-based measurements. Among ABP parameters, diastolic pressure is a stronger predictor than systolic pressure due to its closer association with vascular resistance and perfusion in small cerebral vessels. Additionally, 24 h systolic BP profiles are linked to short-term stroke recurrence, and comprehensive ABP profiling may aid in early detection of recurrent events [17].

Nocturnal hypertension, defined by home or ambulatory SBP ≥120 mm Hg during sleep, is associated with increased cardiovascular risk, including a 2.65-fold higher risk of stroke [18]. This risk is further elevated in atrial fibrillation patients with a reverse-dipper BP pattern and in those with reduced nocturnal BP dips [19], such as patients on HeartMate II support [20]. Incorporating sleep duration and nocturnal BP into cardiovascular risk models significantly improves stroke prediction (C-statistic: 0.795). These findings underscore the importance of managing nocturnal hypertension and maintaining optimal sleep duration to reduce stroke risk [21]. Additionally, distinct circadian BP patterns observed in AIS may reflect sympathetic nervous system activity and stress responses, warranting further investigation into their clinical relevance [22].

OSA is a prevalent sleep-related breathing disorder marked by recurrent upper airway obstruction during sleep, leading to oxygen desaturation, sleep fragmentation, and heightened sympathetic activity [23]. Meta-analyses have shown that OSA is associated with a twofold increased risk of stroke (RR ≈ 2.0) [24]. Case–control studies further support this link, showing higher rates of cardioembolic stroke in patients with OSA and a 50% increase in recurrent stroke or TIA among those with SDB [25]. A summary of these findings is presented in Table S2 [5,26,27,28,29,30,31,32,33,34].

The pathogenesis of OSA is multifactorial, involving autonomic, hemodynamic, and biochemical dysregulation [35]. Intermittent hypoxia during apneic episodes activates the sympathetic nervous system, leading to elevated vascular resistance, systemic inflammation, and increased levels of catecholamines, angiotensin II, and endothelin-1. These changes contribute to the development of hypertension, cardiovascular disease, and heightened stroke risk [36].

Insomnia is defined by difficulty initiating or maintaining sleep, with awakenings lasting over 30 min occurring at least three times per week. It is classified as short-term if lasting less than three months and chronic if persisting longer [63]. Nearly 50% of stroke patients experience insomnia in the early post-stroke period, with 33% reporting it as a new symptom and the remainder as a recurrence [64,65]. Approximately 30% of stroke survivors report insomnia, which is often associated with elevated anxiety levels and greater functional disability [66].

In a pediatric population study of 16,609 individuals aged 18 or younger, sleep-disordered breathing (SDB) was the most common diagnosis, accounting for 11.2% of cases, followed by nocturnal enuresis (1.2%) and insomnia (1%). Sleep disorders were significantly more prevalent among those with multiple chronic medical conditions compared to those with a single condition (19.7% vs. 5.8%, p < 0.001). Additionally, insomnia prevalence was lower among Hispanic (1.2%) and African American (0.8%) children and adolescents compared to Caucasians (3.5%) (p < 0.001) [67]. For detailed studies on insomnia and stroke, refer to Table S3 [68,69,70,71,72,73,74,75,76].

Using EEG, Sterr et al. observed that post-stroke patients exhibited increased sleep latency and reduced sleep efficiency, characterized by prolonged wakefulness after sleep onset and a higher proportion of time spent awake. Despite similar total sleep durations across groups, patients showed greater difficulty initiating sleep during the day and demonstrated increased error rates in vigilance tasks [77].

Zhang et al. investigated potential biochemical markers of post-stroke insomnia (PSI) but found no significant associations with Cell Counting Kit-8 (CCK-8), substance P (SP), or serotonin (5-HT), suggesting the need to explore additional neurotransmitters [48]. In a related study, they assessed serum levels of glutamine (GLN), glutamate (GLU), and gamma-aminobutyric acid (GABA), finding no significant differences between PSI and post-stroke depression groups. However, both groups exhibited significantly lower levels of these neurotransmitters compared to healthy controls, indicating a possible shared neurochemical disruption [48].

Wang et al. demonstrated that post-stroke insomnia is linked to hyperactivation of the DMN and heightened audiovisual sensitivity, disrupting sleep-regulating brain regions [78]. Mayer et al. further identified post-stroke insomnia as a disorder of the brain’s sleep–wake centers, often accompanied by cognitive and emotional impairments, and they found it responds well to cognitive behavioral therapy, antidepressants, melatonin, and GABA agonists [79].

Stroke risk is elevated in individuals under 50 with comorbidities, though it can be reduced through public education, early detection, and effective management [80]. Post-stroke survivors exhibit significantly higher rates of insomnia and related symptoms compared to the general population [65]. Insomnia following stroke is associated with a greater risk of long-term cognitive impairment. Fleming et al. reported that dCBT significantly improves sleep quality, insomnia symptoms, and mood in stroke patients [81]. Additionally, Huang et al. found that combining electroacupuncture with Suanzaoren decoction is more effective and safer for treating post-stroke insomnia than either treatment alone [82].

The severity of insomnia does not significantly influence motor recovery in ischemic stroke patients, where age and NIHSS scores are more predictive of clinical outcomes. However, insomnia remains a critical factor in post-stroke recovery, contributing to anxiety, cognitive decline, and reduced quality of life. Chronic insomnia may be an independent risk factor for stroke, though more standardized studies are needed to confirm this association [83]. The relationship between stroke, insomnia, and conditions like RLS and PLMS is still under investigation. Evidence suggests that supratentorial strokes may disrupt cortical inhibition, potentially triggering PLMS contralateral to the lesion [84]. RLS has also been linked to increased cardiovascular and cerebrovascular risk, including stroke. Digital cognitive behavioral therapy and acupuncture-based treatments have shown promising results in improving sleep and mood outcomes in post-stroke patients [85].

The prevalence of RLS varies geographically, affecting 1–3% of individuals in Asia and 5–13% in Europe and North America [14]. Women are 30–50% more likely to develop RLS than men, with incidence increasing with age, typically beginning in middle age [14]. RLS has been associated with elevated cardiovascular risk as follows: a study of 4000 men found a 2.5-fold increased likelihood of heart problems and a similar link to hypertension [25]. Also, men aged 55–69 reported a 66% higher risk of ischemic stroke in those with RLS. Additionally, patients with end-stage renal disease and RLS had a 2.5-fold increased risk of stroke compared to those without RLS [25]. To further understand the relationship between RLS and stroke, read Table S4 [86,87,88].

RLS is a multifactorial neurological disorder influenced by the following three primary mechanisms: iron deficiency, dopaminergic dysfunction, and genetic predisposition. Iron deficiency in brain regions such as the substantia nigra, putamen, caudate, and thalamus contributes to neuronal hypoxia and demyelination. Dopaminergic abnormalities include elevated dopamine synthesis—evidenced by increased 3-orthomethyl dopamine and reduced fluoro-L-dopa uptake—as well as decreased dopamine transporter availability and D2 receptor density. Genetically, variants in loci such as BTBD9, PTPRD, MAP2K5/SKOR1, MEIS1, and TOX3 have been strongly associated with RLS susceptibility [89].

RBD is characterized by dream enactment behaviors, such as motor activity or vocalizations [90], due to the loss of normal muscle atonia during REM sleep, as confirmed by polysomnography [91]. It affects approximately 11% of stroke survivors and is considered a potential early marker of neurodegenerative disease [1]. Over 90% of individuals with iRBD eventually develop synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, or, less commonly, multiple system atrophy, often more than 15 years after symptom onset [92].

Patients with iRBD often exhibit autonomic dysfunction, such as a non-dipping blood pressure profile, which may contribute to an elevated CVD risk [93]. Sleep-related movement disorders, including RBD, are associated with a significantly increased risk of stroke, with an adjusted hazard ratio of 2.29 (95% CI: 1.42–3.80) [94]. Ma et al. further confirmed that RBD increases the risk of both ischemic and hemorrhagic strokes [95]. While brainstem lesions are implicated in RBD, the disorder is primarily linked to neurodegeneration of glutamatergic neurons in the pons and GABAergic neurons in the medulla [96].

Acute ischemic stroke (AIS) is often followed by a marked reduction in REM sleep, a change that correlates with poorer clinical outcomes. Notably, prolonged REM sleep latency has been identified as an independent predictor of stroke progression. While these findings suggest a potential role of REM sleep in stroke recovery, the underlying mechanisms remain unclear [97].

According to the American Academy of Sleep Medicine, PLMS are defined as repetitive limb movements occurring at a frequency of at least 15 per hour in adults [90]. While commonly associated with RLS, PLMS can also occur in other sleep disorders, medical conditions, or even in healthy individuals [6]. RLS has been linked to increased risks of diabetes, hypertension, obesity [98], and a higher prevalence of coronary artery and cardiovascular disease—particularly in individuals with more frequent or severe symptoms [99]. However, current evidence on RLS as a predictor of cardiovascular events and all-cause mortality remains limited and inconclusive [100]. As Bassetti et al. highlight, further research is needed to clarify the connections between insomnia, RLS/PLMS, and stroke [84].

Del Brutto et al. found no independent association between the periodic limb movement index and neuroimaging markers of cSVD in older adults without a history of stroke [101]. However, genetic studies have linked PLMS to increased risks of stroke, RLS, and insomnia [102]. More recently, Plomaritis et al. reported that severe PLMS occurs in approximately 76% of patients with acute stroke and is associated with poorer outcomes. These findings underscore the importance of early detection and management of PLMS in stroke care [7].

PLMS have been linked to a low respiratory arousal threshold, suggesting a potential connection with the non-anatomical arousal mechanisms seen in OSA [103]. PLMS also appears to accelerate the progression of WMH, serving as a predictor of cSVD burden [104]. Additionally, PLMS is associated with an increased risk of hypertension [105]. While some studies, such as that by Malkiewicz et al., report elevated parasympathetic activity during PLMS episodes, this autonomic co-activation may contribute to fatal cardiac events [106].

Recent studies have shown that working 48–54 h or more per week is associated with an increased risk of stroke [107]. Moderate-grade evidence supports a direct relationship between long working hours and stroke incidence [108]. Theorell et al. suggest that the elevated cardiovascular risk observed in shift workers may be due to acute sympathetic nervous system activation, which disrupts the excretion of catecholamines and alters levels of cholesterol, uric acid, glucose, and potassium [109].

Shift work and extended work hours are associated with both acute and chronic health risks, including metabolic syndrome and certain cancers, due to shared biological pathways [110]. Shift workers exhibit elevated levels of inflammatory markers compared to day workers [111], suggesting a biological link between work schedule demands and chronic disease [112]. Night shift work, in particular, is associated with increased systemic inflammation, notably involving IL-6 [113] and pentraxin 3 [114]. Additionally, shift work has been linked to the early onset of AF, particularly in individuals under 40 years of age over a 10-year follow-up period [115].

In an animal study, Ramsey et al. demonstrated that chronic disruption of the intrinsic sleep–wake cycle—mimicking shift work—impairs stroke recovery, likely through heightened activation of the brain’s immune response. These findings suggest that the negative health effects of shift work may be mitigated through interventions targeting work schedules or inflammatory pathways [116].

Both short- and long-term exposure to night shift work increases the risk of AF, independent of genetic predisposition, and it is also associated with a higher incidence of CHD. However, night shift work does not appear to significantly affect the risk of stroke or heart failure. Skogstad et al. reported that prolonged shift work is linked to preclinical cardiovascular changes, such as increased carotid intima-media thickness and elevated C-reactive protein, indicating a higher risk for CHD and stroke [117]. Additionally, the MTNR1B rs10830963 polymorphism may mediate the relationship between night shift work and stroke risk [118]. Female shift workers are particularly vulnerable to psychological issues, especially depression [119], which itself is associated with a significantly increased risk of stroke (RR = 1.40, 95% CI: 1.27–1.53, p < 0.0001) [120].

Shift workers, particularly those with long-term night shift schedules, have higher odds of CMM related to hypertension compared to day workers [121]. Among female, non-Hispanic White nurses, rotating night shift work was independently associated with an increased risk of ischemic stroke, with a 4% rise in risk for every five years of shift work [122]. While some studies, such as Hermansson’s, did not find a significant difference in stroke risk between shift and day workers [123], more recent evidence indicates a modest but significant increase in stroke risk associated with night shift work (HR 1.13; 95% CI: 1.00–1.28) [118]. Overall, the cumulative data suggest that night shifts and long work hours elevate stroke risk and worsen outcomes, primarily through circadian rhythm disruption and heightened inflammatory responses. Interventions targeting shift patterns or inflammatory pathways may help mitigate these risks.

OSA and CSA are classified under SDB and affect up to 50% of post-stroke patients [135,136]. OSA results from mechanical collapse of the upper airway during sleep, influenced by factors such as age, obesity, male sex, and supine sleeping position (Table S6 [137,138,139,140,141,142]). Reduced tone in pharyngeal dilator muscles like the genioglossus during sleep further contributes to airway narrowing and hypopnea-apnea episodes [136]. These events can lead to hypoventilation, carbon dioxide retention, respiratory acidosis, and sympathetic arousal, often causing sleep fragmentation. CSA, on the other hand, is linked to dysfunction in the brainstem respiratory centers—specifically the dorsal and ventral respiratory groups, the pre-Bötzinger complex, and the pontine pneumotaxic and apneustic centers. Lesions in these areas, common in stroke, can disrupt respiratory rhythm and lead to CSA.

Research on the relationship between stroke lesion location and the incidence of SDB has yielded mixed results. Some case–controlled studies suggest that infratentorial lesions—those affecting the brainstem and cerebellum—are associated with higher AHI scores [135]. Conversely, other studies have found that total anterior circulation strokes, which involve large infarcts in the territories of the anterior and middle cerebral arteries, show the strongest correlation with SDB [143]. A prevailing hypothesis for cortical SDB posits that increased intracranial pressure following stroke may compress respiratory-related neurons, contributing to disordered breathing during sleep.

Stroke incidence follows a bimodal distribution, with peaks occurring in the early morning (6:00 a.m. to 12:00 p.m.) and at night [144]. Epidemiological data show that the morning peak coincides with elevated blood pressure and sympathetic nervous system activity [145]. This increased morning risk appears to be independent of stroke subtype and traditional risk factors such as diabetes and hyperlipidemia. Wake-up strokes present a clinical challenge due to the uncertainty of symptom onset, complicating eligibility for time-sensitive thrombolytic therapy (e.g., tPA), which is recommended within 4.5 h of ischemic stroke onset [146]. These patterns underscore a temporal relationship between stroke occurrence and circadian rhythm disturbances.

The sleep–wake cycle is regulated by several key brain regions, including the pineal gland, the SCN, the sleep-promoting VLPO, and multiple wake-promoting nuclei such as the tuberomammillary nucleus, lateral hypothalamus, locus coeruleus, dorsal raphe, laterodorsal tegmental nucleus, and pedunculopontine tegmental nucleus. Preliminary studies have shown that stroke patients often experience a delayed melatonin rhythm during the acute phase, indicating circadian disruption [147]. Additionally, a 2004 study found that the typical 10% nocturnal blood pressure dip—known as diurnal dipping—was absent in acute stroke patients, further supporting the role of circadian dysregulation in post-stroke physiology [148].

Insomnia, defined as difficulty initiating or maintaining sleep, can present acutely or chronically. Population-based studies estimate that approximately 30% of individuals experience insomnia symptoms [128]. However, when applying stricter diagnostic criteria that include daytime impairment or distress—as outlined by the NIH State-of-the-Science Conference in 2005—the prevalence drops to around 10% [129]. Among stroke patients, 20–56% report insomnia, with 18% experiencing new-onset insomnia following the stroke [130].

The location of a stroke plays a critical role in the development of insomnia due to the involvement of multiple brain regions in sleep–wake regulation. Key structures include the reticular formation in the brainstem, thalamus, hypothalamus, and pineal gland. Strokes affecting the paramedian thalamus can impair the thalamic reticular system, disrupting sleep spindle generation [130]. Focal lesions may also alter neurotransmitter dynamics: the VLPO promotes sleep via GABA and galanin; the locus coeruleus and dorsal raphe nucleus promote wakefulness through norepinephrine and serotonin, respectively; the basal forebrain supports wakefulness and REM sleep via acetylcholine; and the pineal gland regulates circadian rhythms through melatonin secretion. Damage to any of these regions can disrupt sleep architecture, contributing to post-stroke insomnia.

In addition to focal brain lesions, psychosocial factors significantly contribute to post-stroke insomnia. Many stroke survivors experience heightened anxiety about their health and recovery, which can elevate sympathetic nervous system activity. This increased sympathetic tone disrupts normal sleep physiology, leading to reduced sleep quality and difficulty initiating or maintaining sleep.

EDS is commonly reported during the acute phase following a stroke [149,150], with prevalence estimates ranging from 18% to 72%, depending on the assessment method and stroke subtype [151,152,153]. Despite this variability, approximately 34% of stroke survivors experience persistent EDS lasting at least six months post-stroke. EDS can significantly impair recovery and quality of life [154,155]. Hypersomnia, characterized by prolonged sleep during both day and night, reduced activity, and negative impacts on physical and psychological health [156], may also occur post-stroke and can co-occur with other neurological disorders [157].

Hypersomnia following stroke is often associated with lesions in the thalamus, mesencephalon, or pontine tegmental reticular formation [158]. More recently, lesions near the paraventricular nucleus (PVN) of the hypothalamus have also been implicated in newly identified cases of post-stroke hypersomnia, which often improve with recovery [78]. Chen et al. highlighted the central role of PVN dysfunction in hypersomnolence disorder. Specifically, glutamatergic neurons in the PVH^vglut2, including subpopulations such as PVH^OT, PVH^PDYN, and PVH^CRH, are critical for maintaining wakefulness [159].

Post-stroke hypersomnia can result from damage to the ventral lower ARAS [160], a key structure in maintaining wakefulness [161]. It may also occur as a rare manifestation of bilateral thalamic infarcts, which can have severe long-term consequences if not promptly diagnosed and treated [162]. Saida et al. emphasized the importance of considering post-stroke hypersomnia in differential diagnoses, especially in cases of hypersomnolence at work [163]. Cognitive-communication impairments have also been linked to sleep disturbances following brain trauma, with evidence suggesting that pharmacological improvement of sleep can enhance cognitive and communication outcomes [164]. Harris et al. noted that hypersomnia and apathy significantly reduce participation in rehabilitation, leading to poorer recovery [165]. Osman et al. reported a case of hypersomnia following bilateral thalamic stroke, highlighting the diagnostic challenges and the value of early diffusion-weighted MRI in timely detection and intervention [166].

RLS is characterized by an uncontrollable urge to move the legs, often accompanied by crawling, tingling, or burning sensations that are relieved by movement. In contrast, periodic limb movement syndrome (PLMS) involves repetitive, involuntary limb movements during sleep. Post-stroke RLS has been reported in 2.3–15.1% of patients, while post-stroke PLMS is considerably rarer [167]. To date, only 30 cases of post-stroke primary RLS and PLMS have been documented. Focal ischemic lesions in these cases were most commonly located in the pons [168]. Post-stroke RLS typically presents bilaterally and is associated with lesions in the corona radiata and basal ganglia, whereas post-stroke PLMS is usually unilateral and linked to lesions in the pontine base and tegmentum [168]. For a further understanding of sleep-related movement disorders after stroke, read Table S7 [124,168,169,170,171,172,173,174,175].

PSD affects approximately one-third of stroke survivors [176]. Its pathophysiology is multifactorial, involving both psychosocial and biological mechanisms. Functional and cognitive impairments post-stroke are associated with increased depression risk [177], suggesting a psychosocial component [176]. Biologically, PSD has been linked to dysregulation in neurotransmitters, hormones, oxidative stress, and immune responses. Evidence supports a direct neurobiological basis [178], as PSD can occur independently of physical disability and is observed in patients with anosognosia [179]. While lesion location has shown inconsistent associations with PSD, epigenetic factors—such as methylation of the SLC6A4 and BDNF—have been implicated [176]. Additionally, HPA axis overactivation during acute illness may contribute via elevated cytokine and CRH levels [180]. For a summary of all the post-stroke sleep disorders, read Figure S1.

Sleep is a periodic brain state marked by reduced activity and consciousness, regulated by the two-process model: Process C (circadian rhythm) governed by the SCN, and Process S (homeostatic drive) involving sleep-promoting substances like adenosine [211]. Sleep cycles through four NREM stages and one REM stage, with NREM dominated by parasympathetic activity and reduced cerebral perfusion (5–28%) [211], while REM is driven by sympathetic activity and increased perfusion (4–41%) [211]. Central chemoreceptors respond to pCO₂, and these perfusion shifts influence breathing patterns across sleep stages.

Sleep is a complex physiological process essential for brain health and cognitive function [212], comprising distinct stages with specific roles in neural restoration and plasticity [212]. Disruptions—such as insufficient duration, fragmentation, or sleep disorders—can impair cerebral hemodynamics, contributing to neurological deficits. Studies, including those by Somers et al., highlight the strong link between sleep disturbances and cognitive decline. Sleep is broadly divided into NREM (stages N1, N2, and N3) and REM, each with unique electrophysiological and physiological characteristics [213].

As sleep deepens from stage 1 to stage 3, EEG frequency progressively slows, with N3 (deep sleep) dominated by delta waves (1–4 Hz) [214], reflecting reduced neuronal activity and metabolic demand [215]. In contrast, REM sleep features vivid dreams, muscle atonia [216], and increased theta (4–10 Hz) and gamma (35–58 Hz) activity in the cortex and hippocampus, indicating heightened neuronal activity and brain function [217,218]. REM sleep behavior disorder disrupts this normal REM pattern.

Sleep is accompanied by characteristic physiological changes: heart rate and blood pressure decline during NREM sleep, reaching their lowest in deep sleep (N3), while REM sleep shows marked fluctuations, often exceeding waking levels [219]. These changes reflect autonomic nervous system activity and influence cerebral hemodynamics [219]. Adequate sleep—7–9 h for young and middle-aged adults—is essential for cognitive performance, immune function, and hormonal balance. Chronic sleep deprivation or disruption can impair brain function and cognition [220].

Intrinsic cerebral hemodynamics—the regulation of blood flow within the brain—is essential for maintaining brain health. NVC, also known as functional hyperemia, ensures that active brain regions receive adequate blood supply [221]. Triggered by increased neuronal activity, NVC involves local arteriole vasodilation to deliver oxygen and nutrients, supporting metabolic demands and cognitive function [222].

Cerebral autoregulation maintains stable CBF despite fluctuations in systemic blood pressure by adjusting the diameter of cerebral arterioles [223]. Impairment of this mechanism can lead to hypoperfusion or hyperperfusion, increasing the risk of ischemic injury or damage to sensitive brain regions. CVR reflects the brain’s ability to dilate vessels in response to stimuli like hypercapnia or hypoxia, serving as an important indicator of vascular health [224].

Several techniques are used to assess cerebral hemodynamics. Transcranial Doppler ultrasonography non-invasively measures blood flow velocity in major cerebral arteries. fMRI detects BOLD signals, reflecting neuronal activity via deoxyhemoglobin changes [225]. fNIRS tracks hemoglobin concentration shifts to assess cortical blood volume and oxygenation [226]. DVA measures retinal microvessel diameter, offering insights into cerebrovascular reactivity and microvascular health [227].

Neuropsychological tests like CANTAB and n-back consistently show that sleep deprivation impairs reaction time, sustained attention, and working memory [228,229,230]. Transcranial Doppler studies reveal altered CBF patterns in sleep-deprived individuals, suggesting disrupted regulatory mechanisms [231]. NIRS also shows reduced hemodynamic responses in the prefrontal cortex, indicating impaired NVC [232,233]. These effects may stem from dysfunctions in neurons, astrocytes, and endothelial cells. Sleep deprivation lowers neuronal activity and metabolic demand, contributing to reduced CBF and altered vascular tone [234]. Astrocyte dysfunction further disrupts synaptic plasticity and NVC [235]. In OSA, repeated airway obstruction causes intermittent hypoxia and blood pressure surges, compounding the negative impact on cerebral hemodynamics [236,237].

TCD and NIRS studies show that repeated physiological insults in OSA lead to increased variability in CBF and oxygenation, highlighting a volatile hemodynamic environment [238,239]. Chronic intermittent hypoxia contributes to endothelial dysfunction and impaired CVR by disrupting nitric oxide production and promoting oxidative stress [240]. Additionally, autonomic imbalance—marked by heightened sympathetic and reduced parasympathetic activity—further disrupts cerebrovascular regulation in OSA [213].

While sleep deprivation is a known risk factor, prolonged sleep duration has also been linked to increased stroke risk [241]. This may be due to elevated PWV, indicating arterial stiffness, and a higher likelihood of cardiometabolic dysfunction [242]. Additionally, oversleeping is often associated with reduced physical activity [243], contributing to poorer overall health and increased cerebrovascular vulnerability [244].

The relationship between sleep and stroke recovery is complex and multi-dimensional [245]. Emerging evidence highlights the critical role of both sleep macrostructure and microstructure in brain repair and functional recovery. Far from being passive, sleep actively supports memory consolidation, synaptic plasticity, metabolic regulation, and immune modulation [246,247]. Disruptions to these processes after stroke can hinder neural repair and reorganization, ultimately affecting recovery outcomes [245].

Sleep macrostructure refers to the overall architecture of sleep, including wakefulness, NREM stages 1–3, and REM sleep, along with their durations throughout the night [245]. Typically assessed via PSG, it reflects sleep continuity, quality, and stage distribution—key indicators of brain health. Numerous PSG studies have reported significant macrostructural disruptions in stroke patients [248], especially during the acute post-stroke phase [249,250].

A common finding in stroke patients is reduced TST [251], often accompanied by decreased sleep efficiency—the proportion of time asleep while in bed [252]—indicating fragmented and less restorative sleep [249]. These patients also tend to experience increased sleep latency, reflecting difficulty initiating sleep and more frequent arousals, particularly in the acute post-stroke phase [253,254].

Stroke can alter specific sleep stages, particularly SWS, NREM stage 3, and REM [245]. SWS, marked by high-voltage slow brain waves, supports memory consolidation, synaptic plasticity, and metabolic waste clearance [247]. Studies show a consistent reduction in SWS duration and percentage in stroke patients, potentially impairing these restorative functions and slowing recovery [252].

The impact of stroke on REM sleep remains unclear. Some studies report reduced REM sleep in acute stroke patients, suggesting a link to stroke severity [254], while others find no consistent changes [249]. This inconsistency underscores the limitations of sleep macrostructure analysis, which, though informative about stage durations, does not capture the brain’s detailed electrical activity—highlighting the importance of examining sleep microstructure for a deeper understanding [245].

Sleep microstructure refers to the subtle, fine-grained electrical activity of the brain during sleep that may be overlooked by conventional staging. Quantitative EEG is a powerful tool for analyzing microstructure, enabling objective measurement of brain wave frequencies and revealing patterns of activity across sleep stages that may influence key physiological processes [255].

qEEG studies in stroke patients consistently show reduced delta and sigma power during NREM sleep [255]. Lower delta activity reflects impaired deep sleep, potentially affecting restorative functions and synaptic plasticity [252]. Reduced sigma power, indicating fewer sleep spindles [255]—brief 11–16 Hz bursts during stage 2 NREM—suggests deficits in memory consolidation and sensory gating [256]. These impairments may hinder recovery by disrupting core sleep-dependent brain processes [257].

Beyond spindle density, examining spindle characteristics such as amplitude and duration may offer deeper insights into the link between sleep microstructure and stroke recovery [258,259]. Studies have shown that reduced spindle density and amplitude are associated with a higher risk of developing hypertension—a major complication in stroke patients [258]. Studies have shown that reduced spindle density and amplitude are associated with a higher risk of developing hypertension—a major complication in stroke patients.

These findings underscore the critical role of sleep microstructure in stroke recovery and highlight the need for a more comprehensive research approach [245]. While macrostructural and microstructural analyses each provide valuable insights, neither alone captures the full spectrum of neurophysiological changes during sleep. A combined approach is essential for identifying sleep features that predict recovery outcomes and for developing targeted interventions to enhance sleep quality and support brain healing and reorganization in stroke patients [245].

Long-term adherence to PAP therapy ranges from 65% to 80% after four years []. Adherence improves with patient education on the benefits of PAP and risks of obstructive sleep apnea (OSA), as well as behavioral strategies like cognitive behavioral therapy (CBT) and motivational enhancement. The Centers for Medicare & Medicaid Services defines adherence as using PAP for ≥4 h per night on ≥5 nights per week. In a cohort of 2.6 million patients initiating PAP between 2014 and 2017, 75% met this criterion, with an average use of 6 h per night on 93% of nights []. ^{276 276}

Some studies suggest that CPAP therapy may enhance stroke rehabilitation outcomes [,]. However, initiating CPAP soon after stroke is challenging, with adherence rates as low as 12–25% []. Stroke patients with OSA differ from the general OSA population, often presenting with lower body weight and fewer classic symptoms like excessive sleepiness or snoring [,]. They also experience greater functional impairments—such as limb weakness, dysphagia, aphasia, and cognitive deficits—which can reduce CPAP tolerance. Psychological factors like post-stroke depression, anxiety, fatigue, and pain further complicate adherence []. The Sleep Apnea Cardiovascular Endpoints (SAVE) trial (), a large multicenter RCT, is evaluating whether CPAP reduces cardiovascular events in patients with CVD and moderate-to-severe OSA. Outcomes are expected to be closely tied to CPAP adherence []. ^{314 315 316 317 318 262 319} NCT00738179

Although CPAP effectively eliminates SDB events and alleviates OSA symptoms, long-term adherence remains a challenge. Nonadherence—defined as using CPAP for less than 4 h per night—has been reported in 29% to 83% of patients []. Greater nightly usage is associated with improved OSA symptoms, reduced daytime sleepiness, better quality of life, and lower blood pressure [,]. Evidence suggests that adherence patterns are often established within the first week of therapy [,]. However, no single factor consistently predicts CPAP use, and demographic variables such as age, sex, and marital status have not shown reliable associations with adherence []. Instead, adherence appears to be influenced by a complex, individualized set of factors. ^{320 321 322 323 324 325}

Studies show limited and inconsistent correlations between CPAP adherence and OSA severity, as measured by AHI, ODI, or daytime sleepiness [,]. However, there is a lack of consistent evidence to support this claim []. The SAVE trial, which began in China and later expanded to Australia and New Zealand, highlights the need for more diverse population data. While African American patients have shown lower adherence compared to Caucasians, little is known about CPAP usage patterns in other ethnic groups. One study in Chinese patients found that a higher baseline AHI was the only independent predictor of better CPAP adherence at 1 and 3 months []. ^{326 327 323 328}

The AHI has long been the standard for diagnosing OSA and assessing cardiovascular risk. However, recent studies challenge its sufficiency, revealing that AHI alone may not capture the full spectrum of sleep-related stroke risk. The DREAM cohort identified seven independent polysomnographic phenotypes associated with cardiovascular outcomes, including stroke, highlighting the need for broader metrics such as hypoxic burden, ODI, and HRV in risk stratification [329].

Emerging evidence also suggests that reduced HRV may serve as a sensitive marker for stroke risk in OSA patients. Additionally, quantitative EEG studies have identified specific brain wave alterations—such as changes in delta, alpha, and beta power, and ratios like DAR and DTABR—that may indicate increased vulnerability to ischemia, even in individuals without diagnosed OSA [72].

Sleep disorders are increasingly recognized as heterogeneous conditions with distinct phenotypes and variable stroke risk profiles. This understanding supports a shift toward personalized medicine in stroke care. For example, Ye et al. identified three OSA phenotypes based on symptom clusters, with the “minimal symptom” group paradoxically showing higher odds of hypertension and cardiovascular disease [330].

Similar findings from international studies, including SAGIC, confirm the existence of multiple OSA subtypes across populations, reinforcing the need for individualized treatment strategies based on sleep phenotype [331,332].

Genetic research is uncovering loci associated with susceptibility to both sleep disorders and stroke, offering new avenues for risk assessment and targeted interventions. Additionally, race, ethnicity, and sex significantly influence the sleep–stroke relationship. For instance, African American patients have shown lower CPAP adherence, and the study by Appelros et al. highlights how stroke risk and presentation vary by demographic factors, including sex and age. These findings underscore the importance of culturally and biologically tailored public health strategies [333].

While CPAP remains the gold standard for OSA treatment, adherence challenges have spurred interest in enhancing its effectiveness and exploring alternatives. Behavioral interventions, telemedicine, and smart CPAP technologies have shown promise in improving compliance. For example, Bakker et al. demonstrated that increased motivation correlates with longer CPAP use [334], and Kotzian et al. showed that telemonitoring improves adherence in post-stroke patients [210].

Alternative therapies—such as hypoglossal nerve stimulation, positional therapy, oral appliances, and expiratory positive airway pressure (EPAP)—are being explored for CPAP-intolerant individuals, though more clinical trials are needed to confirm their long-term efficacy and safety in stroke populations.

The timing of OSA treatment post-stroke is also under investigation. Trials like Sleep SMART are evaluating whether early intervention can reduce recurrent stroke risk and improve functional outcomes, potentially reshaping post-stroke care.

Advancements in neuroimaging and electrophysiology are shedding light on how sleep disorders influence stroke risk and recovery. Disrupted sleep has been linked to impaired neurovascular coupling (NVC), altered brain plasticity, and heightened inflammatory responses. Functional imaging studies, such as those by Jensen et al., suggest that CPAP therapy may help restore cerebral blood flow (CBF) in response to hypoxia, potentially normalizing NVC in OSA patients.

Further research using diffusion tensor imaging (DTI) and functional MRI (fMRI) could clarify how OSA treatment influences brain plasticity and recovery post-stroke. In parallel, inflammation is emerging as a key mediator in the sleep–stroke relationship. Monsour et al. highlighted the role of oxidative stress and inflammation in linking OSA to ischemic stroke, suggesting that anti-inflammatory effects of OSA treatment may offer neuroprotective benefits [335].

An exciting frontier is the gut–brain axis. Emerging evidence suggests that the gut microbiome may influence sleep quality, circadian rhythms, and stroke risk. Understanding this relationship could lead to novel, non-invasive interventions targeting microbiota to improve sleep and reduce stroke vulnerability.