Strengths, weaknesses, opportunities, and threats of using AI-enabled technology in sleep medicine: a commentary.

Over the past few years, artificial intelligence (AI) has emerged as a powerful tool used to efficiently automate several tasks across multiple domains. Sleep medicine is perfectly positioned to leverage this tool due to the wealth of physiological signals obtained through sleep studies or sleep tracking devices and abundance of accessible clinical data through electronic medical records. However, caution must be applied when utilizing AI, due to intrinsic challenges associated with novel technology. The Artificial Intelligence in Sleep Medicine Committee of the American Academy of Sleep Medicine reviews advancements in AI within the sleep medicine field. In this article, the Artificial Intelligence in Sleep Medicine committee members provide a commentary on the scope of AI technology in sleep medicine. The commentary identifies 3 pivotal areas in sleep medicine that can benefit from AI technologies: clinical care, lifestyle management, and population health management. This article provides a detailed analysis of the strengths, weaknesses, opportunities, and threats associated with using AI-enabled technologies in each pivotal area. Finally, the article broadly reviews barriers and challenges associated with using AI-enabled technologies and offers possible solutions. CITATION: Bandyopadhyay A, Oks M, Sun H, et al. Strengths, weaknesses, opportunities, and threats of using AI-enabled technology in sleep medicine: a commentary. J Clin Sleep Med. 2024;20(7):1183-1191.

Rapid Eye Movement Sleep Behavior Disorder: Management and Prognostic Counseling.

Management of rapid eye movement sleep behavior disorder (RBD) includes reducing injurious dream-enactment behaviors, risk of injury to self and bedpartner, and vivid or disruptive dreams and improving sleep quality and bedpartner sleep disruption. Safety precautions should be reviewed at each visit. Medications to reduce RBD symptoms such as melatonin, clonazepam, pramipexole, and rivastigmine should be considered for most patients. Isolated RBD confers a high lifetime risk of neurodegenerative diseases with a latency often spanning many years. A patient-centered shared decision-making approach to risk disclosure is recommended. Knowledge of the risk allows for life planning and participation in research.

REM Sleep Behavior Disorder and Other REM Parasomnias.

OBJECTIVE: This article reviews rapid eye movement (REM) sleep behavior disorder (RBD) and other REM sleep parasomnias, particularly recurrent isolated sleep paralysis and nightmare disorder. LATEST DEVELOPMENTS: People with RBD have dream enactment behaviors that can be distressing and cause injuries to themselves or a bed partner. Diagnosis of RBD still requires video polysomnography but new evaluative techniques are emerging. Automatic scoring of REM sleep without atonia, the polysomnographic RBD feature, has led to clearer diagnostic cutoff values. Isolated RBD is strongly linked with neurodegenerative disorders, particularly α-synucleinopathies, with a median latency to neurodegenerative disease diagnosis of 8 years. Mounting imaging, electrophysiologic, and pathologic evidence supports neurodegenerative changes in patients with isolated RBD. Safety precautions should be reviewed with patients to reduce the risk of injury. Clonazepam and melatonin are first-line agents for RBD symptoms, and rivastigmine appears to be beneficial for RBD in people with mild cognitive impairment. For nightmare disorder, image rehearsal therapy is effective and can be delivered through online platforms. ESSENTIAL POINTS: While RBD symptoms can often be managed, patients with isolated RBD should be monitored for signs and symptoms of impending neurodegenerative disease. Individuals who wish to know about the associated risk should be counseled accordingly to allow planning and involvement in research if they choose. Exercise may have some neuroprotective effects, although no treatment has been shown to modify the neurodegenerative risk.

Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

This systematic review provides supporting evidence for a clinical practice guideline for the management of rapid eye movement (REM) sleep behavior disorder in adults and children. The American Academy of Sleep Medicine commissioned a task force of 7 experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials and observational studies that addressed interventions for the management of REM sleep behavior disorder in adults and children. Statistical analyses were performed to determine the clinical significance of critical and important outcomes. Finally, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search identified 4,690 studies; 148 studies provided data suitable for statistical analyses; evidence for 45 interventions is presented. The task force provided a detailed summary of the evidence assessing the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2023;19(4):769-810.

Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for the management of rapid eye movement sleep behavior disorder (RBD) in adults. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENT: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RBD: It is critically important to help patients maintain a safe sleeping environment to prevent potentially injurious nocturnal behaviors. In particular, the removal of bedside weapons, or objects that could inflict injury if thrown or wielded against a bed partner, is of paramount importance. Sharp furniture like nightstands should be moved away or their edges and headboard should be padded. To reduce the risk of injurious falls, a soft carpet, rug, or mat should be placed next to the bed. Patients with severe, uncontrolled RBD should be recommended to sleep separately from their partners, or at the minimum, to place a pillow between themselves and their partners. RECOMMENDATIONS: The following recommendations, with medications listed in alphabetical order, are a guide for clinicians in choosing a specific treatment for RBD in adults. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the patient's values and preferences to determine the best course of action.Adult patients with isolated RBD.1. The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).2. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).3. * The AASM suggests that clinicians use pramipexole (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).4. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of isolated RBD in adults with mild cognitive impairment. (CONDITIONAL).Adult patients with secondary RBD due to medical condition.5. * The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).6. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).7. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of secondary RBD due to medical condition (Parkinson disease) in adults. (CONDITIONAL).8. * The AASM suggests that clinicians not use deep brain stimulation (DBS; vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).Adult patients with drug-induced RBD.9. * The AASM suggests that clinicians use drug discontinuation (vs drug continuation) for the treatment of drug-induced RBD in adults. (CONDITIONAL).* The Recommendations section of this paper includes remarks that provide additional context to guide clinicians with implementation of this recommendation. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2023;19(4):759-768.

Brain Stimulation for Improving Sleep and Memory.

Over the past few decades, the importance of sleep has become increasingly recognized for many physiologic functions, including cognition. Many studies have reported the deleterious effect of sleep loss or sleep disruption on cognitive performance. Beyond ensuring adequate sleep quality and duration, discovering methods to enhance sleep to augment its restorative effects is important to improve learning in many populations, such as the military, students, age-related cognitive decline, and cognitive disorders.

Sleep Dysfunction in Movement Disorders: a Window to the Disease Biology.

PURPOSE OF REVIEW: To comprehensively summarize the sleep pathologies associated with movement disorders, focusing on neurodegenerative diseases. RECENT FINDINGS: Mounting evidence has further implicated both sleep and circadian disruption in the pathophysiology of many movement disorders. In particular, recent data illuminate the mechanisms by which poor sleep quality and circadian dysfunction can exacerbate neurodegeneration. In addition, anti-IgLON5 disease is a recently described autoimmune disease with various symptoms that can feature prominent sleep disruption and parasomnia. Many movement disorders are associated with sleep and circadian rhythm disruption. Motor symptoms can cause sleep fragmentation, resulting in insomnia and excessive daytime sleepiness. Many neurodegenerative movement disorders involve brainstem pathology in regions close to or affecting nuclei that regulate sleep and wake. Further, commonly used movement medications may exacerbate sleep concerns. Providers should screen for and address these sleep symptoms to improve function and quality of life for patients and caregivers.

Light exposure during sleep impairs cardiometabolic function.

SignificanceAmbient nighttime light exposure is implicated as a risk factor for adverse health outcomes, including cardiometabolic disease. However, the effects of nighttime light exposure during sleep on cardiometabolic outcomes and the related mechanisms are unclear. This laboratory study shows that, in healthy adults, one night of moderate (100 lx) light exposure during sleep increases nighttime heart rate, decreases heart rate variability (higher sympathovagal balance), and increases next-morning insulin resistance when compared to sleep in a dimly lit (<3 lx) environment. Moreover, a positive relationship between higher sympathovagal balance and insulin levels suggests that sympathetic activation may play a role in the observed light-induced changes in insulin sensitivity.

A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance.

STUDY OBJECTIVES: This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. METHODS: A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. RESULTS: A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. CONCLUSIONS: Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303. CITATION: Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med. 2022;18(3):789-800.

REM Sleep Behavior Disorder as a Pathway to Dementia: If, When, How, What, and Why Should Physicians Disclose the Diagnosis and Risk for Dementia.

Purpose of Review: People with isolated REM (rapid eye movement) sleep behavior disorder (iRBD) have a high lifetime risk of developing a neurodegenerative disease, including dementia, but disclosure of this risk remains controversial. Herein, we summarize this controversy and provide guidance on disclosure. Recent Findings: Neurodegeneration risk disclosure in iRBD is controversial because of a long latency to disease onset and a lack of preventative strategies. Balancing the relevant ethical principles of beneficence, nonmaleficence, and autonomy is challenging. Although there are few data on disclosure in iRBD, evidence from discussing risk in other diseases with dementia provides some guidance. Summary: We provide an approach to risk disclosure for patients with iRBD. Patients should be asked if they want to know about future risks. If so, disclosure should be patient centered, focusing on what might happen. Discussion should occur early to give patients time to prepare for the future and consider participating in research.

Effects of manipulating body temperature on sleep in postmenopausal women.

STUDY OBJECTIVES: A decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post-menopausal women. METHODS: Twenty-four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8-h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively. RESULTS: In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5-1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001). CONCLUSIONS: The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women.

Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep-wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Autonomic dysregulation and sleep homeostasis in insomnia.

STUDY OBJECTIVES: Insomnia is common in older adults, and is associated with poor health, including cognitive impairment and cardio-metabolic disease. Although the mechanisms linking insomnia with these comorbidities remain unclear, age-related changes in sleep and autonomic nervous system (ANS) regulation might represent a shared mechanistic pathway. In this study, we assessed the relationship between ANS activity with indices of objective and subjective sleep quality in older adults with insomnia. METHODS: Forty-three adults with chronic insomnia and 16 age-matched healthy sleeper controls were studied. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), objective sleep quality by electroencephalogram spectral components derived from polysomnography, and ANS activity by measuring 24-h plasma cortisol and norepinephrine (NE). RESULTS: Sleep cycle analysis displayed lower slow oscillatory (SO: 0.5-1.25 Hz) activity in the first cycle in insomnia compared to controls. In insomnia, 24-h cortisol levels were higher and 24-h NE levels were lower than controls. In controls, but not in insomnia, there was a significant interaction between NE level during wake and SO activity levels across the sleep cycles, such that in controls but not in insomnia, NE level during wake was positively associated with the amount of SO activity in the first cycle. In insomnia, lower 24-h NE level and SO activity in the first sleep cycle were associated with poorer subjective sleep quality. CONCLUSION: Dysregulation of autonomic activity may be an underlying mechanism that links objective and subjective measures of sleep quality in older adults with insomnia, and potentially contribute to adverse health outcomes.

Sleep Medicine Milestones 2.0: designed for our field.

NONE: The Accreditation Council for Graduate Medical Education published the first sleep medicine milestones in 2015. However, these milestones were the same among all internal medicine fellowship programs; they were not specific to the specialty. Based on stakeholder feedback, the Accreditation Council for Graduate Medical Education called for the creation of specialty-specific milestones. Herein, we outline the history of Accreditation Council for Graduate Medical Education reporting milestones; the identification of knowledge, skills, and attitudes that define the practice of sleep medicine; and the creation of the supplemental guide and sleep medicine-specific milestones (Sleep Medicine Milestones 2.0) to assess developmental progression during fellowship training.

Obstructive Sleep Apnea and Risk of COVID-19 Infection, Hospitalization and Respiratory Failure.

PURPOSE: To study the relationship between OSA and risk of COVID-19 infection and disease severity, identified by the need for hospitalization and progression to respiratory failure. METHODS: We queried the electronic medical record system for an integrated health system of 10 hospitals in the Chicago metropolitan area to identify cases of COVID-19. Comorbidities and outcomes were ascertained by ICD-10-CM coding and medical record data. We evaluated the risk for COVID-19 diagnosis, hospitalization, and respiratory failure associated with OSA by univariate tests and logistic regression, adjusting for diabetes, hypertension, and BMI to account for potential confounding in the association between OSA, COVID-19 hospitalization, and progression to respiratory failure. RESULTS: We identified 9405 COVID-19 infections, among which 3185 (34%) were hospitalized and 1779 (19%) were diagnosed with respiratory failure. OSA was more prevalent among patients requiring hospitalization than those who did not (15.3% versus 3.4%, p < 0.0001; OR 5.20, 95% CI (4.43, 6.12)), and among those who progressed to respiratory failure (19.4% versus 4.5%, p < 0.0001; OR 5.16, 95% CI (4.41, 6.03)). After adjustment for diabetes, hypertension, and BMI, OSA was associated with increased risk for hospitalization (OR 1.65; 95% CI (1.36, 2.02)) and respiratory failure (OR 1.98; 95% CI (1.65, 2.37)). CONCLUSIONS: Patients with OSA experienced approximately 8-fold greater risk for COVID-19 infection compared to a similar age population receiving care in a large, racially, and socioeconomically diverse healthcare system. Among patients with COVID-19 infection, OSA was associated with increased risk of hospitalization and approximately double the risk of developing respiratory failure.

Neurostimulation techniques to enhance sleep and improve cognition in aging.

Sleep plays a critical role in the process of memory consolidation. In particular, during non-rapid eye movement (NREM) slow wave sleep, slow-oscillations, spindles, hippocampal sharp wave ripples, and their phase coupling are involved in the process of transferring and consolidating information recently encoded and temporarily stored in the hippocampus into long-term memory stored in the neocortex. There is evidence that aging and neurodegenerative conditions, in particular Alzheimer's disease, are associated with changes to this transient grouping of NREM oscillations. Therefore, methods to enhance sleep, particularly slow wave sleep, have the potential to improve cognitive performance. Transcranial electrical and magnetic stimulation have been shown useful to enhance sleep slow-waves and sleep-dependent memory consolidation, however there is need for more information regarding proper protocols of application and applicability and efficacy in patients with neurodegenerative conditions. Acoustic stimulation during sleep has been proven particularly effective in enhancing sleep slow-waves and spindles with associated improvement in overnight memory consolidation. More importantly, preliminary data indicate that similar results can be achieved in healthy older adults and those with amnestic mild cognitive impairment. Studies are needed to optimize the modalities of acoustic stimulation during sleep, which may vary based on age group or clinical disorder. Overall, non-invasive techniques of neurostimulation may represent a valid approach to mitigate cognitive decline associated with aging and neurodegeneration. Furthermore, they offer the unique opportunity to improve our understanding of the physiology behind sleep-dependent memory consolidation.

A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia: main outcomes from the MATRICS study.

STUDY OBJECTIVES: To investigate treatment models using cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) for people with obstructive sleep apnea (OSA) and comorbid insomnia. METHODS: 121 adults with OSA and comorbid insomnia were randomized to receive CBT-I followed by PAP, CBT-I concurrent with PAP, or PAP only. PAP was delivered following standard clinical procedures for in-lab titration and home setup and CBT-I was delivered in four individual sessions. The primary outcome measure was PAP adherence across the first 90 days, with regular PAP use (≥4 h on ≥70% of nights during a 30-day period) serving as the clinical endpoint. The secondary outcome measures were the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with good sleeper (PSQI <5), remission (ISI <8), and response (ISI reduction from baseline >7) serving as the clinical endpoints. RESULTS: No significant differences were found between the concomitant treatment arms and PAP only on PAP adherence measures, including the percentage of participants who met the clinical endpoint. Compared to PAP alone, the concomitant treatment arms reported a significantly greater reduction from baseline on the ISI (p = .0009) and had a greater percentage of participants who were good sleepers (p = .044) and remitters (p = .008). No significant differences were found between the sequential and concurrent treatment models on any outcome measure. CONCLUSIONS: The findings from this study indicate that combining CBT-I with PAP is superior to PAP alone on insomnia outcomes but does not significantly improve adherence to PAP.

Brain Stimulation for Improving Sleep and Memory.

Given the critical role of sleep, particularly sleep slow oscillations, sleep spindles, and hippocampal sharp wave ripples, in memory consolidation, sleep enhancement represents a key opportunity to improve cognitive performance. Techniques such as transcranial electrical and magnetic stimulation and acoustic stimulation can enhance slow oscillations and sleep spindles and potentially improve memory. Targeted memory reactivation in sleep may enhance or stabilize memory consolidation. Each technique has technical considerations that may limit its broader clinical application. Therefore, neurostimulation to enhance sleep quality, in particular sleep slow oscillations, has the potential for improving sleep-related memory consolidation in healthy and clinical populations.

Circadian disruption and human health: A bidirectional relationship.

Circadian rhythm disorders have been classically associated with disorders of abnormal timing of the sleep-wake cycle, however circadian dysfunction can play a role in a wide range of pathology, ranging from the increased risk for cardiometabolic disease and malignancy in shift workers, prompting the need for a new field focused on the larger concept of circadian medicine. The relationship between circadian disruption and human health is bidirectional, with changes in circadian amplitude often preceding the classical symptoms of neurodegenerative disorders. As our understanding of the importance of circadian dysfunction in disease grows, we need to develop better clinical techniques for identifying circadian rhythms and also develop circadian based strategies for disease management. Overall this review highlights the need to bring the concept of time to all aspects of medicine, emphasizing circadian medicine as a prime example of both personalized and precision medicine.