Sleep as the Foundation of Brain Health

Abstract

Sleep is a vital function, taking about one-third of a human lifetime, and is essential for achieving and maintaining brain health. From homeostatic neurophysiology to emotional and procedural memory processing to clearance of brain waste, sleep and circadian alignment remain paramount. Yet modern lifestyles and clinical practice often dismiss sleep, resulting in profound long-term repercussions. This chapter examines the roles of sleep and circadian rhythms in memory consolidation, synaptic plasticity, and clearance of metabolic waste, highlighting recent advances in neuroscience research. We explore how insufficient and disordered sleep—a public health concern—can impair cognition, escalate neurodegenerative risks, and compromise neurovascular integrity, thereby impacting brain health. These findings underscore the need for comprehensive screening for disturbed sleep and targeted interventions in clinical practice. Emerging interventions and AI-driven technologies may allow early detection and personalized and individualized treatments and improve outcomes. Overall, this chapter reaffirms that healthy sleep is indispensable at any level of neurological disease prevention—on par with the role of diet and exercise in cardiovascular health—and represents the foundation of brain health.

Keywords

neurodegeneration - stroke - sleep deprivation - circadian rhythm - glymphatic system - memory

Publication History

Accepted Manuscript online:
26 March 2025

Article published online:
25 April 2025

• References

• 1 Klinzing JG, Niethard N, Born J. Mechanisms of systems memory consolidation during sleep. Nat Neurosci 2019; 22 (10) 1598-1610
• 2 Wang G, Grone B, Colas D, Appelbaum L, Mourrain P. Synaptic plasticity in sleep: learning, homeostasis and disease. Trends Neurosci 2011; 34 (09) 452-463
• 3 Nedergaard M, Goldman SA. Glymphatic failure as a final common pathway to dementia. Science 2020; 370 (6512) 50-56
• 4 Golombek DA, Booi L, Campbell D. et al. Sleep diplomacy: an approach to boosting global brain health. Lancet Healthy Longev 2023; 4 (08) e368-e370
• 5 Watson NF, Badr MS, Belenky G. et al; Consensus Conference Panel, Non-Participating Observers, American Academy of Sleep Medicine Staff. Recommended amount of sleep for a healthy adult: a joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 2015; 11 (06) 591-592
• 6 Lim DC, Najafi A, Afifi L. et al; World Sleep Society Global Sleep Health Taskforce. The need to promote sleep health in public health agendas across the globe. Lancet Public Health 2023; 8 (10) e820-e826
• 7 Ibrahim A, Högl B, Stefani A. The bidirectional relationship between sleep and neurodegeneration: actionability to improve brain health. Clinical and Translational Neuroscience 2024; 8: 11
• 8 Mayer-Suess L, Ibrahim A, Moelgg K. et al. Sleep disorders as both risk factors for, and a consequence of, stroke: a narrative review. Int J Stroke 2024; 19 (05) 490-498
• 9 Mirmiran M, Scholtens J, van de Poll NE, Uylings HB, van der Gugten J, Boer GJ. Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat. Brain Res 1983; 283 (2-3): 277-286
• 10 Borbély AA. Circadian rhythm of vigilance in rats: modulation by short light-dark cycles. Neurosci Lett 1975; 1 (01) 67-71
• 11 Borbély A. The two-process model of sleep regulation: beginnings and outlook. J Sleep Res 2022; 31 (04) e13598
• 12 Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron 2017; 93 (04) 747-765
• 13 Morairty SR, Dittrich L, Pasumarthi RK. et al. A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity. Proc Natl Acad Sci U S A 2013; 110 (50) 20272-20277
• 14 Eban-Rothschild A, Appelbaum L, de Lecea L. Neuronal mechanisms for sleep/wake regulation and modulatory drive. Neuropsychopharmacology 2018; 43 (05) 937-952
• 15 Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol 2018; 175 (16) 3190-3199
• 16 Leng Y, Musiek ES, Hu K, Cappuccio FP, Yaffe K. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol 2019; 18 (03) 307-318
• 17 Logan RW, McClung CA. Rhythms of life: circadian disruption and brain disorders across the lifespan. Nat Rev Neurosci 2019; 20 (01) 49-65
• 18 Chen CY, Logan RW, Ma T. et al. Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc Natl Acad Sci U S A 2016; 113 (01) 206-211
• 19 Klein R, Klein BE. The prevalence of age-related eye diseases and visual impairment in aging: current estimates. Invest Ophthalmol Vis Sci 2013; 54 (14) F5 , F13
• 20 Drake CL, Roehrs T, Richardson G, Walsh JK, Roth T. Shift work sleep disorder: prevalence and consequences beyond that of symptomatic day workers. Sleep 2004; 27 (08) 1453-1462
• 21 Lee KW, Yang CC, Chen CH, Hung CH, Chuang HY. Shift work is significantly and positively associated with dementia: a meta-analysis study. Front Public Health 2023; 11: 998464
• 22 Teichman EM, O'Riordan KJ, Gahan CGM, Dinan TG, Cryan JF. When rhythms meet the blues: circadian interactions with the microbiota-gut-brain axis. Cell Metab 2020; 31 (03) 448-471
• 23 Verma AK, Singh S, Rizvi SI. Therapeutic potential of melatonin and its derivatives in aging and neurodegenerative diseases. Biogerontology 2023; 24 (02) 183-206
• 24 Bocheva G, Bakalov D, Iliev P, Tafradjiiska-Hadjiolova R. The vital role of melatonin and its metabolites in the neuroprotection and retardation of brain aging. Int J Mol Sci 2024; 25 (10) 25
• 25 Troester MQuan SF, Berry RB. et al, for the American Academy of Sleep Medicine; The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Version 3:. Dariel, IL: American Academy of Sleep Medicine; 2023
• 26 Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep 2004; 27 (07) 1255-1273
• 27 Taporoski TP, Beijamini F, Alexandria S. et al. Gender differences in the relationship between sleep and age in a Brazilian cohort: the Baependi Heart Study. J Sleep Res 2024; e14154
• 28 Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA 2000; 284 (07) 861-868
• 29 Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW. Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 1997; 276 (5316) 1265-1268
• 30 Bjorness TE, Dale N, Mettlach G. et al. An adenosine-mediated glial-neuronal circuit for homeostatic sleep. J Neurosci 2016; 36 (13) 3709-3721
• 31 Hu Z, Lee CI, Shah VK. et al. Cordycepin increases nonrapid eye movement sleep via adenosine receptors in rats. Evid Based Complement Alternat Med 2013; 2013: 840134
• 32 Feldberg W, Sherwood SL. Behaviour of cats after intraventricular injections of eserine and DFP. J Physiol 1954; 125 (03) 488-500
• 33 Benington JH, Kodali SK, Heller HC. Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res 1995; 692 (1-2): 79-85
• 34 Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev 1992; 17 (02) 139-170
• 35 Arnaud MJ. The pharmacology of caffeine. Prog Drug Res 1987; 31: 273-313
• 36 Oike H, Kobori M, Suzuki T, Ishida N. Caffeine lengthens circadian rhythms in mice. Biochem Biophys Res Commun 2011; 410 (03) 654-658
• 37 Pagnussat N, Almeida AS, Marques DM. et al. Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice. Br J Pharmacol 2015; 172 (15) 3831-3845
• 38 Borota D, Murray E, Keceli G. et al. Post-study caffeine administration enhances memory consolidation in humans. Nat Neurosci 2014; 17 (02) 201-203
• 39 Cao C, Loewenstein DA, Lin X. et al. High blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimers Dis 2012; 30 (03) 559-572
• 40 Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N. Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimers Dis 2010; 20 (Suppl. 01) S187-S204
• 41 Lopes JP, Pliássova A, Cunha RA. The physiological effects of caffeine on synaptic transmission and plasticity in the mouse hippocampus selectively depend on adenosine A₁ and A_2A receptors. Biochem Pharmacol 2019; 166: 313-321
• 42 Ji Q, Yang Y, Xiong Y. et al. Blockade of adenosine A_2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer's disease by promoting synaptic plasticity of adult-born granule cells. Alzheimers Res Ther 2023; 15 (01) 187
• 43 Carvalho K, Faivre E, Pietrowski MJ. et al; NeuroCEB Brain Bank. Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor. Brain 2019; 142 (11) 3636-3654
• 44 Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H. Coffee and green tea consumption and cardiovascular disease mortality among people with and without hypertension. J Am Heart Assoc 2023; 12 (02) e026477
• 45 Kim E, Robinson NM, Newman BM. A brewed awakening: neuropsychiatric effects of caffeine in older adults. Clin Geriatr Med 2022; 38 (01) 133-144
• 46 Kromhout MA, Rius Ottenheim N, Giltay E, Numans ME, Achterberg WP. Caffeine and neuropsychiatric symptoms in patients with dementia: a systematic review. Exp Gerontol 2019; 122: 85-91
• 47 Kromhout MA, Jongerling J, Achterberg WP. Relation between caffeine and behavioral symptoms in elderly patients with dementia: an observational study. J Nutr Health Aging 2014; 18 (04) 407-410
• 48 de Pooter-Stijnman LMM, Vrijkotte S, Smalbrugge M. Effect of caffeine on sleep and behaviour in nursing home residents with dementia. Eur Geriatr Med 2018; 9 (06) 829-835
• 49 Lin YS, Weibel J, Landolt HP. et al. Daily caffeine intake induces concentration-dependent medial temporal plasticity in humans: a multimodal double-blind randomized controlled trial. Cereb Cortex 2021; 31 (06) 3096-3106
• 50 Lin YS, Lange D, Baur DM. et al. Repeated caffeine intake suppresses cerebral grey matter responses to chronic sleep restriction in an A₁ adenosine receptor-dependent manner: a double-blind randomized controlled study with PET-MRI. Sci Rep 2024; 14 (01) 12724
• 51 Korman M, Doyon J, Doljansky J, Carrier J, Dagan Y, Karni A. Daytime sleep condenses the time course of motor memory consolidation. Nat Neurosci 2007; 10 (09) 1206-1213
• 52 Baena D, Cantero JL, Fuentemilla L, Atienza M. Weakly encoded memories due to acute sleep restriction can be rescued after one night of recovery sleep. Sci Rep 2020; 10 (01) 1449
• 53 Ribeiro N, Gounden Y, Quaglino V. A full night's sleep at home improves memory performance in an associative and relational learning task. Dreaming 2020; 30 (02) 171-188
• 54 Tucker MA, Hirota Y, Wamsley EJ, Lau H, Chaklader A, Fishbein W. A daytime nap containing solely non-REM sleep enhances declarative but not procedural memory. Neurobiol Learn Mem 2006; 86 (02) 241-247
• 55 Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci 2003; 6 (07) 697-698
• 56 Lahl O, Wispel C, Willigens B, Pietrowsky R. An ultra short episode of sleep is sufficient to promote declarative memory performance. J Sleep Res 2008; 17 (01) 3-10
• 57 Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci 2010; 11 (02) 114-126
• 58 Gais S, Lucas B, Born J. Sleep after learning aids memory recall. Learn Mem 2006; 13 (03) 259-262
• 59 Holz J, Piosczyk H, Landmann N. et al. The timing of learning before night-time sleep differentially affects declarative and procedural long-term memory consolidation in adolescents. PLoS One 2012; 7 (07) e40963
• 60 Maquet P. The role of sleep in learning and memory. Science 2001; 294 (5544) 1048-1052
• 61 Gais S, Plihal W, Wagner U, Born J. Early sleep triggers memory for early visual discrimination skills. Nat Neurosci 2000; 3 (12) 1335-1339
• 62 Fogel SM, Smith CT, Cote KA. Dissociable learning-dependent changes in REM and non-REM sleep in declarative and procedural memory systems. Behav Brain Res 2007; 180 (01) 48-61
• 63 Rasch B, Büchel C, Gais S, Born J. Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 2007; 315 (5817) 1426-1429
• 64 Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science 1994; 265 (5172) 676-679
• 65 Rosanova M, Ulrich D. Pattern-specific associative long-term potentiation induced by a sleep spindle-related spike train. J Neurosci 2005; 25 (41) 9398-9405
• 66 Morin A, Doyon J, Dostie V. et al. Motor sequence learning increases sleep spindles and fast frequencies in post-training sleep. Sleep 2008; 31 (08) 1149-1156
• 67 Skilling QM, Eniwaye B, Clawson BC. et al. Acetylcholine-gated current translates wake neuronal firing rate information into a spike timing-based code in Non-REM sleep, stabilizing neural network dynamics during memory consolidation. PLOS Comput Biol 2021; 17 (09) e1009424
• 68 Bellfy L, Smies CW, Bernhardt AR. et al. The clock gene Per1 may exert diurnal control over hippocampal memory consolidation. Neuropsychopharmacology 2023; 48 (12) 1789-1797
• 69 Iliff JJ, Wang M, Liao Y. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012; 4 (147) 147ra111
• 70 Mestre H, Tithof J, Du T. et al. Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension. Nat Commun 2018; 9 (01) 4878
• 71 Xie L, Kang H, Xu Q. et al. Sleep drives metabolite clearance from the adult brain. Science 2013; 342 (6156) 373-377
• 72 Hablitz LM, Vinitsky HS, Sun Q. et al. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv 2019; 5 (02) eaav5447
• 73 Hablitz LM, Plá V, Giannetto M. et al. Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun 2020; 11 (01) 4411
• 74 Eide PK, Vinje V, Pripp AH, Mardal KA, Ringstad G. Sleep deprivation impairs molecular clearance from the human brain. Brain 2021; 144 (03) 863-874
• 75 Han F, Chen J, Belkin-Rosen A. et al; Alzheimer's Disease Neuroimaging Initiative. Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology. PLoS Biol 2021; 19 (06) e3001233
• 76 Miao A, Luo T, Hsieh B. et al. Brain clearance is reduced during sleep and anesthesia. Nat Neurosci 2024; 27 (06) 1046-1050
• 77 Henríquez-Beltrán M, Dreyse J, Jorquera J. et al. The U-shaped association between sleep duration, all-cause mortality and cardiovascular risk in a Hispanic/Latino clinically based cohort. J Clin Med 2023; 12 (15) 4961
• 78 You Y, Chen Y, Liu R. et al. Inverted U-shaped relationship between sleep duration and phenotypic age in US adults: a population-based study. Sci Rep 2024; 14 (01) 6247
• 79 Dong L, Xie Y, Zou X. Association between sleep duration and depression in US adults: a cross-sectional study. J Affect Disord 2022; 296: 183-188
• 80 Alhola P, Polo-Kantola P. Sleep deprivation: impact on cognitive performance. Neuropsychiatr Dis Treat 2007; 3 (05) 553-567
• 81 Lucey BP, Hicks TJ, McLeland JS. et al. Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics. Ann Neurol 2018; 83 (01) 197-204
• 82 Arrigoni E, Chamberlin NL, Saper CB, McCarley RW. Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro. Neuroscience 2006; 140 (02) 403-413
• 83 Maurer SV, Williams CL. The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Front Immunol 2017; 8: 1489
• 84 Shokri-Kojori E, Wang GJ, Wiers CE. et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci U S A 2018; 115 (17) 4483-4488
• 85 Sabia S, Fayosse A, Dumurgier J. et al. Association of sleep duration in middle and old age with incidence of dementia. Nat Commun 2021; 12 (01) 2289
• 86 Ibrahim A, Cesari M, Heidbreder A. et al. Sleep features and long-term incident neurodegeneration: a polysomnographic study. Sleep 2024; 47 (03) 47
• 87 Windred DP, Burns AC, Lane JM. et al. Sleep regularity is a stronger predictor of mortality risk than sleep duration: a prospective cohort study. Sleep 2024; 47 (01) 253
• 88 Wang JL, Lim AS, Chiang WY. et al. Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans. Ann Neurol 2015; 78 (02) 317-322
• 89 Cermakian N, Lamont EW, Boudreau P, Boivin DB. Circadian clock gene expression in brain regions of Alzheimer's disease patients and control subjects. J Biol Rhythms 2011; 26 (02) 160-170
• 90 Iranzo A. Sleep in neurodegenerative diseases. Sleep Med Clin 2016; 11 (01) 1-18
• 91 Stefani A, Högl B. Sleep in Parkinson's disease. Neuropsychopharmacology 2020; 45 (01) 121-128
• 92 Galbiati A, Verga L, Giora E, Zucconi M, Ferini-Strambi L. The risk of neurodegeneration in REM sleep behavior disorder: a systematic review and meta-analysis of longitudinal studies. Sleep Med Rev 2019; 43: 37-46
• 93 Postuma RB, Iranzo A, Hu M. et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 2019; 142 (03) 744-759
• 94 Iranzo A, Stefani A, Serradell M. et al; SINBAR (Sleep Innsbruck Barcelona) group. Characterization of patients with longstanding idiopathic REM sleep behavior disorder. Neurology 2017; 89 (03) 242-248
• 95 Yaffe K, Laffan AM, Harrison SL. et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 2011; 306 (06) 613-619
• 96 Blackwell T, Yaffe K, Ancoli-Israel S. et al; Osteoporotic Fractures in Men Study Group. Associations between sleep architecture and sleep-disordered breathing and cognition in older community-dwelling men: the Osteoporotic Fractures in Men Sleep Study. J Am Geriatr Soc 2011; 59 (12) 2217-2225
• 97 Blackwell T, Yaffe K, Laffan A. et al; Osteoporotic Fractures in Men (MrOS) Study Group. Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study. Sleep 2014; 37 (04) 655-663
• 98 Osorio RS, Gumb T, Pirraglia E. et al; Alzheimer's Disease Neuroimaging Initiative. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology 2015; 84 (19) 1964-1971
• 99 Lutsey PL, Misialek JR, Mosley TH. et al. Sleep characteristics and risk of dementia and Alzheimer's disease: The Atherosclerosis Risk in Communities Study. Alzheimers Dement 2018; 14 (02) 157-166
• 100 Leng Y, McEvoy CT, Allen IE, Yaffe K. Association of sleep-disordered breathing with cognitive function and risk of cognitive impairment: a systematic review and meta-analysis. JAMA Neurol 2017; 74 (10) 1237-1245
• 101 Dunietz GL, Chervin RD, Burke JF, Conceicao AS, Braley TJ. Obstructive sleep apnea treatment and dementia risk in older adults. Sleep 2021; 44 (09) 44
• 102 André C, Kuhn E, Rehel S. et al; Medit-Ageing Research Group. Association of sleep-disordered breathing and medial temporal lobe atrophy in cognitively unimpaired amyloid-positive older adults. Neurology 2023; 101 (04) e370-e385
• 103 Leonhard AG, Kapur VK. Beyond traditional hypoxemia metrics: hypoxic burden as a predictor of cognitive dysfunction in sleep apnea. Sleep (Basel) 2025; 48 (03) zsae292
• 104 Breen DP, Williams-Gray CH, Mason SL, Foltynie T, Barker RA. Excessive daytime sleepiness and its risk factors in incident Parkinson's disease. J Neurol Neurosurg Psychiatry 2013; 84 (02) 233-234
• 105 Sohail S, Yu L, Schneider JA, Bennett DA, Buchman AS, Lim ASP. Sleep fragmentation and Parkinson's disease pathology in older adults without Parkinson's disease. Mov Disord 2017; 32 (12) 1729-1737
• 106 Osorio RS, Pirraglia E, Agüera-Ortiz LF. et al. Greater risk of Alzheimer's disease in older adults with insomnia. J Am Geriatr Soc 2011; 59 (03) 559-562
• 107 Pase MP, Himali JJ, Grima NA. et al. Sleep architecture and the risk of incident dementia in the community. Neurology 2017; 89 (12) 1244-1250
• 108 Otaiku AI. Association of sleep abnormalities in older adults with risk of developing Parkinson's disease. Sleep 2022; 45 (11) 45
• 109 Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A. Sundowning and circadian rhythms in Alzheimer's disease. Am J Psychiatry 2001; 158 (05) 704-711
• 110 Del Olmo M, Schmal C, Mizaikoff C. et al. Are circadian amplitudes and periods correlated? A new twist in the story. F1000 Res 2024; 12: 1077
• 111 Breen DP, Vuono R, Nawarathna U. et al. Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol 2014; 71 (05) 589-595
• 112 Hooghiemstra AM, Eggermont LH, Scheltens P, van der Flier WM, Scherder EJ. The rest-activity rhythm and physical activity in early-onset dementia. Alzheimer Dis Assoc Disord 2015; 29 (01) 45-49
• 113 Naismith SL, Hickie IB, Terpening Z. et al. Circadian misalignment and sleep disruption in mild cognitive impairment. J Alzheimers Dis 2014; 38 (04) 857-866
• 114 Chen S-J, Deng Y-T, Li Y-Z. et al. Association of circadian rhythms with brain disorder incidents: a prospective cohort study of 72242 participants. Transl Psychiatry 2022; 12 (01) 514
• 115 Leng Y, Blackwell T, Cawthon PM, Ancoli-Israel S, Stone KL, Yaffe K. Association of circadian abnormalities in older adults with an increased risk of developing Parkinson disease. JAMA Neurol 2020; 77 (10) 1270-1278
• 116 Musiek ES, Bhimasani M, Zangrilli MA, Morris JC, Holtzman DM, Ju YS. Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurol 2018; 75 (05) 582-590
• 117 Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 2008; 299 (22) 2642-2655
• 118 Videnovic A, Klerman EB, Wang W, Marconi A, Kuhta T, Zee PC. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: a randomized clinical trial. JAMA Neurol 2017; 74 (04) 411-418
• 119 Lee BH, Hille B, Koh DS. Serotonin modulates melatonin synthesis as an autocrine neurotransmitter in the pineal gland. Proc Natl Acad Sci U S A 2021; 118 (43) 118
• 120 Cardoso FDS, Barrett DW, Wade Z, Gomes da Silva S, Gonzalez-Lima F. Photobiomodulation of cytochrome c oxidase by chronic transcranial laser in young and aged brains. Front Neurosci 2022; 16: 818005
• 121 Kress GJ, Liao F, Dimitry J. et al. Regulation of amyloid-β dynamics and pathology by the circadian clock. J Exp Med 2018; 215 (04) 1059-1068
• 122 Ma Z, Jiang W, Zhang EE. Orexin signaling regulates both the hippocampal clock and the circadian oscillation of Alzheimer's disease-risk genes. Sci Rep 2016; 6: 36035
• 123 GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021; 20 (10) 795-820
• 124 Baillieul S, Dekkers M, Brill AK. et al. Sleep apnoea and ischaemic stroke: current knowledge and future directions. Lancet Neurol 2022; 21 (01) 78-88
• 125 Johnson KG, Johnson DC. Frequency of sleep apnea in stroke and TIA patients: a meta-analysis. J Clin Sleep Med 2010; 6 (02) 131-137
• 126 Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 2005; 172 (11) 1447-1451
• 127 Redline S, Yenokyan G, Gottlieb DJ. et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med 2010; 182 (02) 269-277
• 128 Minoguchi K, Yokoe T, Tazaki T. et al. Silent brain infarction and platelet activation in obstructive sleep apnea. Am J Respir Crit Care Med 2007; 175 (06) 612-617
• 129 Lin HJ, Yeh JH, Hsieh MT, Hsu CY. Continuous positive airway pressure with good adherence can reduce risk of stroke in patients with moderate to severe obstructive sleep apnea: an updated systematic review and meta-analysis. Sleep Med Rev 2020; 54: 101354
• 130 Lee SJ, Kim JS, Song IU, An JY, Kim YI, Lee KS. Poststroke restless legs syndrome and lesion location: anatomical considerations. Mov Disord 2009; 24 (01) 77-84
• 131 Winkelman JW, Shahar E, Sharief I, Gottlieb DJ. Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurology 2008; 70 (01) 35-42
• 132 Bertisch SM, Pollock BD, Mittleman MA. et al. Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study. Sleep 2018; 41 (06) 41
• 133 Sawadogo W, Adera T, Alattar M, Perera R, Burch JB. Association between insomnia symptoms and trajectory with the risk of stroke in the Health and Retirement Study. Neurology 2023; 101 (05) e475-e488
• 134 Luo Y, Yu G, Liu Y, Zhuge C, Zhu Y. Sleep quality after stroke: a systematic review and meta-analysis. Medicine (Baltimore) 2023; 102 (20) e33777
• 135 Miano S, Fanfulla F, Nobili L. et al. SAS CARE 1: sleep architecture changes in a cohort of patients with ischemic stroke/TIA. Sleep Med 2022; 98: 106-113
• 136 Duss SB, Bauer-Gambelli SA, Bernasconi C. et al. Frequency and evolution of sleep-wake disturbances after ischemic stroke: a 2-year prospective study of 437 patients. Sleep Med 2023; 101: 244-251
• 137 Varadharasu S, Das N. Sleep hygiene efficacy on quality of sleep and mental ability among insomniac patients. J Family Med Prim Care 2024; 13 (10) 4693-4698
• 138 Riemann D, Baglioni C, Bassetti C. et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res 2017; 26 (06) 675-700
• 139 Siengsukon CF, Nelson E, Williams-Cooke C. et al. Cognitive behavioral therapy for insomnia to enhance cognitive function and reduce the rate of Aβ deposition in older adults with symptoms of insomnia: a single-site randomized pilot clinical trial protocol. Contemp Clin Trials 2020; 99: 106190
• 140 Zhang Z, Xue P, Bendlin BB. et al. Melatonin: a potential nighttime guardian against Alzheimer's. Mol Psychiatry 2025; 30 (01) 237-250
• 141 Sumsuzzman DM, Choi J, Jin Y, Hong Y. Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer's disease and insomnia: a systematic review and meta-analysis of randomized controlled trials. Neurosci Biobehav Rev 2021; 127: 459-473
• 142 Obayashi K, Saeki K, Iwamoto J. et al. Physiological levels of melatonin relate to cognitive function and depressive symptoms: the HEIJO-KYO cohort. J Clin Endocrinol Metab 2015; 100 (08) 3090-3096
• 143 Mignot E, Mayleben D, Fietze I. et al; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol 2022; 21 (02) 125-139
• 144 Zhou M, Tang S. Effect of a dual orexin receptor antagonist on Alzheimer's disease: sleep disorders and cognition. Front Med (Lausanne) 2023; 9: 984227
• 145 Evans R, Kimura H, Alexander R. et al. Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proc Natl Acad Sci U S A 2022; 119 (35) e2207531119
• 146 Suresh V, Bardhan M, Ghosh S. et al. Exploring the role of Orexin-A neuropeptide in Parkinson's disease: a systematic review and meta-analysis. Clin Neurol Neurosurg 2024; 242: 108320
• 147 Cesari M, Stefani A, Penzel T. et al. Interrater sleep stage scoring reliability between manual scoring from two European sleep centers and automatic scoring performed by the artificial intelligence-based Stanford-STAGES algorithm. J Clin Sleep Med 2021; 17 (06) 1237-1247
• 148 Cesari M, Portscher A, Stefani A. et al. Machine learning predicts phenoconversion from polysomnography in isolated REM sleep behavior disorder. Brain Sci 2024; 14 (09) 871
• 149 Zhao H, Cao J, Xie J. et al. Wearable sensors and features for diagnosis of neurodegenerative diseases: a systematic review. Digit Health 2023;9:20552076231173569
• 150 Stephansen JB, Olesen AN, Olsen M. et al. Neural network analysis of sleep stages enables efficient diagnosis of narcolepsy. Nat Commun 2018; 9 (01) 5229
• 151 de Zambotti M, Goldstein C, Cook J. et al. State of the science and recommendations for using wearable technology in sleep and circadian research. Sleep 2024; 47 (04) 47
• 152 Thirunavukarasu AJ, Ting DSJ, Elangovan K, Gutierrez L, Tan TF, Ting DSW. Large language models in medicine. Nat Med 2023; 29 (08) 1930-1940