Sleep Alterations and Cognitive Decline

Abstract

Sleep disturbances and cognitive decline are intricately connected, and both are prevalent in aging populations and individuals with neurodegenerative disorders such as Alzheimer's disease (AD) and other dementias. Sleep is vital for cognitive functions including memory consolidation, executive function, and attention. Disruption in these processes is associated with cognitive decline, although causal evidence is mixed. This review delves into the bidirectional relationship between alterations in sleep and cognitive impairment, exploring key mechanisms such as amyloid-β accumulation, tau pathology, synaptic homeostasis, neurotransmitter dysregulation, oxidative stress, and vascular contributions. Evidence from both experimental research and population-based studies underscores the necessity of early interventions targeting sleep to mitigate risks of neurodegenerative diseases. A deeper understanding of the interplay between sleep and cognitive health may pave the way for innovative strategies to prevent or reduce cognitive decline through improved sleep management.

Keywords

cognition - sleep - sleep disorders - aging - neurodegeneration

Publication History

Accepted Manuscript online:
13 March 2025

Article published online:
03 April 2025

• References

• 1 Prince M, Wimo A, Guerchet M. et al. World Alzheimer Report 2015: The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends. In. London; 2015
• 2 Li J, Vitiello MV, Gooneratne NS. Sleep in normal aging. Sleep Med Clin 2018; 13 (01) 1-11
• 3 Ju Y-E, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology–a bidirectional relationship. Nat Rev Neurol 2014; 10 (02) 115-119
• 4 Mander BA, Winer JR, Jagust WJ, Walker MP. Sleep: a novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer's disease?. Trends Neurosci 2016; 39 (08) 552-566
• 5 Lucey BP. It's complicated: the relationship between sleep and Alzheimer's disease in humans. Neurobiol Dis 2020; 144: 105031
• 6 McConnell BV, Deng Y, Lucey BP. Sleep and Neurodegeneration: examining potential physiological mechanisms. Curr Sleep Med Rep 2025; 11: 1
• 7 Walker MP. The role of slow wave sleep in memory processing. J Clin Sleep Med 2009; 5 (2, suppl) S20-S26
• 8 Scullin MK. Sleep, memory, and aging: the link between slow-wave sleep and episodic memory changes from younger to older adults. Psychol Aging 2013; 28 (01) 105-114
• 9 Klinzing JG, Niethard N, Born J. Mechanisms of systems memory consolidation during sleep. Nat Neurosci 2019; 22 (10) 1598-1610
• 10 Marshall L, Born J. The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn Sci 2007; 11 (10) 442-450
• 11 Buzsáki G. Hippocampal sharp wave-ripple: a cognitive biomarker for episodic memory and planning. Hippocampus 2015; 25 (10) 1073-1188
• 12 Sanda P, Malerba P, Jiang X. et al. Bidirectional interaction of hippocampal ripples and cortical slow waves leads to coordinated spiking activity during NREM sleep. Cereb Cortex 2021; 31 (01) 324-340
• 13 Yang W, Sun C, Huszár R, Hainmueller T, Kiselev K, Buzsáki G. Selection of experience for memory by hippocampal sharp wave ripples. Science 2024; 383 (6690): 1478-1483
• 14 Geva-Sagiv M, Nir Y. Local sleep oscillations: implications for memory consolidation. Front Neurosci 2019; 13: 813
• 15 Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci 2010; 11 (02) 114-126
• 16 Adamantidis AR, Gutierrez Herrera C, Gent TC. Oscillating circuitries in the sleeping brain. Nat Rev Neurosci 2019; 20 (12) 746-762
• 17 Girardeau G, Lopes-Dos-Santos V. Brain neural patterns and the memory function of sleep. Science 2021; 374 (6567): 560-564
• 18 Latchoumane CV, Ngo HV, Born J, Shin HS. Thalamic spindles promote memory formation during sleep through triple phase-locking of cortical, thalamic, and hippocampal rhythms. Neuron 2017; 95 (02) 424-435.e6
• 19 Maingret N, Girardeau G, Todorova R, Goutierre M, Zugaro M. Hippocampo-cortical coupling mediates memory consolidation during sleep. Nat Neurosci 2016; 19 (07) 959-964
• 20 Geva-Sagiv M, Mankin EA, Eliashiv D. et al. Augmenting hippocampal-prefrontal neuronal synchrony during sleep enhances memory consolidation in humans. Nat Neurosci 2023; 26 (06) 1100-1110
• 21 Kim J, Gulati T, Ganguly K. Competing roles of slow oscillations and delta waves in memory consolidation versus forgetting. Cell 2019; 179 (02) 514-526.e13
• 22 Muehlroth BE, Sander MC, Fandakova Y. et al. Precise slow oscillation-spindle coupling promotes memory consolidation in younger and older adults. Sci Rep 2019; 9 (01) 1940
• 23 Helfrich RF, Mander BA, Jagust WJ, Knight RT, Walker MP. Old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting. Neuron 2018; 97 (01) 221-230.e4
• 24 Rauchs G, Bertran F, Guillery-Girard B. et al. Consolidation of strictly episodic memories mainly requires rapid eye movement sleep. Sleep 2004; 27 (03) 395-401
• 25 Nishida M, Pearsall J, Buckner RL, Walker MP. REM sleep, prefrontal theta, and the consolidation of human emotional memory. Cereb Cortex 2009; 19 (05) 1158-1166
• 26 Cai DJ, Mednick SA, Harrison EM, Kanady JC, Mednick SC. REM, not incubation, improves creativity by priming associative networks. Proc Natl Acad Sci U S A 2009; 106 (25) 10130-10134
• 27 Stickgold R, Walker MP. Sleep-dependent memory triage: evolving generalization through selective processing. Nat Neurosci 2013; 16 (02) 139-145
• 28 Montgomery SM, Sirota A, Buzsáki G. Theta and gamma coordination of hippocampal networks during waking and rapid eye movement sleep. J Neurosci 2008; 28 (26) 6731-6741
• 29 de Almeida-Filho DG, Koike BDV, Billwiller F. et al. Hippocampus-retrosplenial cortex interaction is increased during phasic REM and contributes to memory consolidation. Sci Rep 2021; 11 (01) 13078
• 30 Ramirez-Villegas JF, Besserve M, Murayama Y, Evrard HC, Oeltermann A, Logothetis NK. Coupling of hippocampal theta and ripples with pontogeniculooccipital waves. Nature 2021; 589 (7840): 96-102
• 31 Boyce R, Glasgow SD, Williams S, Adamantidis A. Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science 2016; 352 (6287): 812-816
• 32 Puentes-Mestril C, Roach J, Niethard N, Zochowski M, Aton SJ. How rhythms of the sleeping brain tune memory and synaptic plasticity. Sleep 2019; 42 (07) 42
• 33 Lendner JD, Niethard N, Mander BA. et al. Human REM sleep recalibrates neural activity in support of memory formation. Sci Adv 2023; 9 (34) eadj1895
• 34 Jones K, Harrison Y. Frontal lobe function, sleep loss and fragmented sleep. Sleep Med Rev 2001; 5 (06) 463-475
• 35 Harrison Y, Horne JA. The impact of sleep deprivation on decision making: a review. J Exp Psychol Appl 2000; 6 (03) 236-249
• 36 Horne JA. Sleep loss and “divergent” thinking ability. Sleep 1988; 11 (06) 528-536
• 37 Harrison Y, Horne JA. Sleep deprivation affects speech. Sleep 1997; 20 (10) 871-877
• 38 Gottselig JM, Adam M, Rétey JV, Khatami R, Achermann P, Landolt HP. Random number generation during sleep deprivation: effects of caffeine on response maintenance and stereotypy. J Sleep Res 2006; 15 (01) 31-40
• 39 Hsieh S, Cheng IC, Tsai LL. Immediate error correction process following sleep deprivation. J Sleep Res 2007; 16 (02) 137-147
• 40 Lim J, Dinges DF. Sleep deprivation and vigilant attention. Ann N Y Acad Sci 2008; 1129: 305-322
• 41 Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol 2005; 25 (01) 117-129
• 42 Leng Y, Knutson K, Carnethon MR, Yaffe K. Association between sleep quantity and quality in early adulthood with cognitive function in midlife. Neurology 2024; 102 (02) e208056
• 43 Li P, Gao L, Yu L. et al. Daytime napping and Alzheimer's dementia: a potential bidirectional relationship. Alzheimers Dement 2023; 19 (01) 158-168
• 44 Vaz Fragoso CA, Gill TM. Sleep complaints in community-living older persons: a multifactorial geriatric syndrome. J Am Geriatr Soc 2007; 55 (11) 1853-1866
• 45 Patel D, Steinberg J, Patel P. Insomnia in the elderly: a review. J Clin Sleep Med 2018; 14 (06) 1017-1024
• 46 Fortier-Brochu E, Morin CM. Cognitive impairment in individuals with insomnia: clinical significance and correlates. Sleep 2014; 37 (11) 1787-1798
• 47 Ancoli-Israel S, Cooke JR. Prevalence and comorbidity of insomnia and effect on functioning in elderly populations. J Am Geriatr Soc 2005; 53 (7, suppl) S264-S271
• 48 Buysse DJ, Thompson W, Scott J. et al. Daytime symptoms in primary insomnia: a prospective analysis using ecological momentary assessment. Sleep Med 2007; 8 (03) 198-208
• 49 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
• 50 Tworoger SS, Lee S, Schernhammer ES, Grodstein F. The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women. Alzheimer Dis Assoc Disord 2006; 20 (01) 41-48
• 51 Faubel R, López-García E, Guallar-Castillón P, Graciani A, Banegas JR, Rodríguez-Artalejo F. Usual sleep duration and cognitive function in older adults in Spain. J Sleep Res 2009; 18 (04) 427-435
• 52 Kronholm E, Sallinen M, Suutama T, Sulkava R, Era P, Partonen T. Self-reported sleep duration and cognitive functioning in the general population. J Sleep Res 2009; 18 (04) 436-446
• 53 Xu L, Jiang CQ, Lam TH. et al. Short or long sleep duration is associated with memory impairment in older Chinese: the Guangzhou Biobank Cohort Study. Sleep 2011; 34 (05) 575-580
• 54 Potvin O, Lorrain D, Forget H. et al. Sleep quality and 1-year incident cognitive impairment in community-dwelling older adults. Sleep 2012; 35 (04) 491-499
• 55 Mohlenhoff BS, Insel PS, Mackin RS. et al. Total sleep time interacts with age to predict cognitive performance among adults. J Clin Sleep Med 2018; 14 (09) 1587-1594
• 56 Ding G, Li J, Lian Z. Both short and long sleep durations are associated with cognitive impairment among community-dwelling Chinese older adults. Medicine (Baltimore) 2020; 99 (13) e19667
• 57 Ma Y, Liang L, Zheng F, Shi L, Zhong B, Xie W. Association between sleep duration and cognitive decline. JAMA Netw Open 2020; 3 (09) e2013573
• 58 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
• 59 Lucey BP, Wisch J, Boerwinkle AH. et al. Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer's disease. Brain 2021; 144 (09) 2852-2862
• 60 Keil SA, Schindler AG, Wang MX. et al. Longitudinal sleep patterns and cognitive impairment in older adults. JAMA Netw Open 2023; 6 (12) e2346006
• 61 Chou CA, Toedebusch CD, Redrick T. et al. Comparison of single-channel EEG, actigraphy, and sleep diary in cognitively normal and mildly impaired older adults. Sleep Adv 2020; 1 (01) zpaa006
• 62 Yaffe K, Falvey CM, Hoang T. Connections between sleep and cognition in older adults. Lancet Neurol 2014; 13 (10) 1017-1028
• 63 Scullin MK, Bliwise DL. Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research. Perspect Psychol Sci 2015; 10 (01) 97-137
• 64 Mander BA, Winer JR, Walker MP. Sleep and human aging. Neuron 2017; 94 (01) 19-36
• 65 Redline S, Kirchner HL, Quan SF, Gottlieb DJ, Kapur V, Newman A. The effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture. Arch Intern Med 2004; 164 (04) 406-418
• 66 Duffy JF, Zitting KM, Chinoy ED. Aging and circadian rhythms. Sleep Med Clin 2015; 10 (04) 423-434
• 67 Wu YH, Swaab DF. The human pineal gland and melatonin in aging and Alzheimer's disease. J Pineal Res 2005; 38 (03) 145-152
• 68 Skene DJ, Swaab DF. Melatonin rhythmicity: effect of age and Alzheimer's disease. Exp Gerontol 2003; 38 (1–2): 199-206
• 69 Boulos MI, Jairam T, Kendzerska T, Im J, Mekhael A, Murray BJ. Normal polysomnography parameters in healthy adults: a systematic review and meta-analysis. Lancet Respir Med 2019; 7 (06) 533-543
• 70 Ancoli-Israel S, Palmer BW, Cooke JR. et al. Cognitive effects of treating obstructive sleep apnea in Alzheimer's disease: a randomized controlled study. J Am Geriatr Soc 2008; 56 (11) 2076-2081
• 71 Cooke JR, Ayalon L, Palmer BW. et al. Sustained use of CPAP slows deterioration of cognition, sleep, and mood in patients with Alzheimer's disease and obstructive sleep apnea: a preliminary study. J Clin Sleep Med 2009; 5 (04) 305-309
• 72 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
• 73 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
• 74 Mander BA, Marks SM, Vogel JW. et al. β-amyloid deposition in the human brain disrupts NREM slow wave sleep and associated hippocampus-dependent long-term memory. Nat Neurosci 2015; 18: 1051-1057
• 75 Tononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron 2014; 81 (01) 12-34
• 76 Zavecz Z, Shah VD, Murillo OG. et al. NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology. BMC Med 2023; 21 (01) 156
• 77 Cirelli C, Tononi G. The why and how of sleep-dependent synaptic down-selection. Semin Cell Dev Biol 2022; 125: 91-100
• 78 Blanco W, Pereira CM, Cota VR. et al. Synaptic homeostasis and restructuring across the sleep-wake cycle. PLOS Comput Biol 2015; 11 (05) e1004241
• 79 Raven F, Van der Zee EA, Meerlo P, Havekes R. The role of sleep in regulating structural plasticity and synaptic strength: implications for memory and cognitive function. Sleep Med Rev 2018; 39: 3-11
• 80 Goto A. Synaptic plasticity during systems memory consolidation. Neurosci Res 2022; 183: 1-6
• 81 Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron 2010; 68 (06) 1023-1042
• 82 Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev 2012; 92 (03) 1087-1187
• 83 Gais S, Born J. Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation. Proc Natl Acad Sci U S A 2004; 101 (07) 2140-2144
• 84 Rasch B, Gais S, Born J. Impaired off-line consolidation of motor memories after combined blockade of cholinergic receptors during REM sleep-rich sleep. Neuropsychopharmacology 2009; 34 (07) 1843-1853
• 85 Atzori M, Paz RD. Interplay Between Dopamine and Acetylcholine in the Modulation of Attention. In: Monoaminergic Modulation of Cortical Excitability. Springer; 2007: 283-297
• 86 Steffens DC, Fahed M, Manning KJ, Wang L. The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research. Transl Psychiatry 2022; 12 (01) 525
• 87 Porkka-Heiskanen T, Strecker RE, McCarley RW. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience 2000; 99 (03) 507-517
• 88 Lanza G, DelRosso LM, Ferri R. Sleep and homeostatic control of plasticity. Handb Clin Neurol 2022; 184: 53-72
• 89 Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer's disease. Nat Rev Dis Primers 2015; 1: 15056
• 90 Meyer-Luehmann M, Stalder M, Herzig MC. et al. Extracellular amyloid formation and associated pathology in neural grafts. Nat Neurosci 2003; 6 (04) 370-377
• 91 Colom-Cadena M, Davies C, Sirisi S. et al. Synaptic oligomeric tau in Alzheimer's disease - a potential culprit in the spread of tau pathology through the brain. Neuron 2023; 111 (14) 2170-2183.e6
• 92 Mudher A, Colin M, Dujardin S. et al. What is the evidence that tau pathology spreads through prion-like propagation?. Acta Neuropathol Commun 2017; 5 (01) 99
• 93 Kang J-E, Lim MM, Bateman RJ. et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science 2009; 326 (5955): 1005-1007
• 94 Holth JK, Fritschi SK, Wang C. et al. The sleep-wake cycle regulates extracellular tau in mice and humans. Science 2019; 363: 880-884
• 95 Huang Y, Potter R, Sigurdson W. et al. Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system. Arch Neurol 2012; 69 (01) 51-58
• 96 Barthélemy NR, Liu H, Lu W, Kotzbauer PT, Bateman RJ, Lucey BP. Sleep deprivation affects tau phosphorylation in human cerebrospinal fluid. Ann Neurol 2020; 87 (05) 700-709
• 97 Zhu Y, Zhan G, Fenik P. et al. Chronic sleep disruption advances the temporal progression of tauopathy in P301S mutant mice. J Neurosci 2018; 38 (48) 10255-10270
• 98 Ju YS, Ooms SJ, Sutphen C. et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain 2017; 140 (08) 2104-2111
• 99 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
• 100 Cirrito JR, Yamada KA, Finn MB. et al. Synaptic activity regulates interstitial fluid amyloid-β levels in vivo. Neuron 2005; 48 (06) 913-922
• 101 Yamada K, Holth JK, Liao F. et al. Neuronal activity regulates extracellular tau in vivo. J Exp Med 2014; 211 (03) 387-393
• 102 Yamada K, Iwatsubo T. Extracellular α-synuclein levels are regulated by neuronal activity. Mol Neurodegener 2018; 13 (01) 9
• 103 Dang-Vu TT, Schabus M, Desseilles M, Sterpenich V, Bonjean M, Maquet P. Functional neuroimaging insights into the physiology of human sleep. Sleep 2010; 33 (12) 1589-1603
• 104 Xiao MF, Roh SE, Zhou J. et al. A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function. Sci Adv 2021; 7 (48) eabf6935
• 105 Barthélemy NR, Li Y, Joseph-Mathurin N. et al; Dominantly Inherited Alzheimer Network. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. Nat Med 2020; 26 (03) 398-407
• 106 Wang Z, Ma J, Miyoshi C. et al. Quantitative phosphoproteomic analysis of the molecular substrates of sleep need. Nature 2018; 558 (7710): 435-439
• 107 Brüning F, Noya SB, Bange T. et al. Sleep-wake cycles drive daily dynamics of synaptic phosphorylation. Science 2019; 366 (6462): eaav3617
• 108 Barthélemy NR, Saef B, Li Y. et al. CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer's disease. Nat Aging 2023; 3 (04) 391-401
• 109 Sims JR, Zimmer JA, Evans CD. et al; TRAILBLAZER-ALZ 2 Investigators. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 2023; 330 (06) 512-527
• 110 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
• 111 Liu H, Barthélemy NR, Ovod V. et al. Acute sleep loss decreases CSF-to-blood clearance of Alzheimer's disease biomarkers. Alzheimers Dement 2023; 19 (07) 3055-3064
• 112 Xie L, Kang H, Xu Q. et al. Sleep drives metabolite clearance from the adult brain. Science 2013; 342 (6156): 373-377
• 113 Eide PK, Lashkarivand A, Pripp AH. et al. Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation. Brain Commun 2023; 5 (06) fcad343
• 114 Eide PK, Lashkarivand A, Pripp A. et al. Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders. Nat Commun 2023; 14 (01) 2084
• 115 Fultz NE, Bonmassar G, Setsompop K. et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 2019; 366 (6465): 628-631
• 116 Vasciaveo V, Iadarola A, Casile A. et al. Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models. Acta Neuropathol Commun 2023; 11 (01) 16
• 117 Fame RM, Kalugin PN, Petrova B. et al. Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution. Nat Commun 2023; 14 (01) 3720
• 118 Da Mesquita S, Louveau A, Vaccari A. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease. Nature 2018; 560 (7717): 185-191
• 119 Picchioni D, Özbay PS, Mandelkow H. et al. Autonomic arousals contribute to brain fluid pulsations during sleep. Neuroimage 2022; 249: 118888
• 120 Pulido RS, Munji RN, Chan TC. et al. Neuronal activity regulates blood-brain barrier efflux transport through endothelial circadian genes. Neuron 2020; 108 (05) 937-952.e7
• 121 Bojarskaite L, Vallet A, Bjørnstad DM. et al. Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport. Nat Commun 2023; 14 (01) 953
• 122 Lucey BP, McCullough A, Landsness EC. et al. Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease. Sci Transl Med 2019; 11 (474) eaau6550
• 123 Pulver RL, Kronberg E, Medenblik LM. et al. Mapping sleep's oscillatory events as a biomarker of Alzheimer's disease. Alzheimers Dement 2024; 20 (01) 301-315
• 124 Ju Y-E, McLeland JS, Toedebusch CD. et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol 2013; 70 (05) 587-593
• 125 Spira AP, Gamaldo AA, An Y. et al. Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol 2013; 70 (12) 1537-1543
• 126 Naismith SL, Leng Y, Palmer JR, Lucey BP. Age differences in the association between sleep and Alzheimer's disease biomarkers in the EPAD cohort. Alzheimers Dement (Amst) 2022; 14 (01) e12380
• 127 Giorgio J, Adams JN, Maass A, Jagust WJ, Breakspear M. Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation. Neuron 2024; 112 (04) 676-686.e4
• 128 Morris HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson's disease. Lancet 2024; 403 (10423): 293-304
• 129 Galvin JE. Lewy body dementia. Continuum (Minneap Minn) 2024; 30 (06) 1673-1698
• 130 Simuni T, Chahine LM, Poston K. et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. Lancet Neurol 2024; 23 (02) 178-190
• 131 Postuma RB, Bertrand JA, Montplaisir J. et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: a prospective study. Mov Disord 2012; 27 (06) 720-726
• 132 Stang CD, Mullan AF, Hajeb M. et al. Timeline of rapid eye movement sleep behavior disorder in overt alpha-synucleinopathies. Ann Neurol 2021; 89 (02) 293-303
• 133 Högl B, Stefani A, Videnovic A. Idiopathic REM sleep behaviour disorder and neurodegeneration - an update. Nat Rev Neurol 2018; 14 (01) 40-55
• 134 Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med 2013; 14 (08) 744-748
• 135 Boeve BF, Silber MH, Ferman TJ. et al. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med 2013; 14 (08) 754-762
• 136 Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 2009; 72 (15) 1296-1300
• 137 Boeve BF, Silber MH, Parisi JE. et al. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology 2003; 61 (01) 40-45
• 138 Boeve BF, Silber MH, Ferman TJ, Lucas JA, Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord 2001; 16 (04) 622-630
• 139 Iranzo A, Cochen De Cock V, Fantini ML, Pérez-Carbonell L, Trotti LM. Sleep and sleep disorders in people with Parkinson's disease. Lancet Neurol 2024; 23 (09) 925-937
• 140 Gottesman RF, Schneider AL, Zhou Y. et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA 2017; 317 (14) 1443-1450
• 141 Ferrari-Souza JP, Brum WS, Hauschild LA. et al; Alzheimer's Disease Neuroimaging Initiative. Vascular risk burden is a key player in the early progression of Alzheimer's disease. Neurobiol Aging 2024; 136: 88-98
• 142 Li M, Hou WS, Zhang XW, Tang ZY. Obstructive sleep apnea and risk of stroke: a meta-analysis of prospective studies. Int J Cardiol 2014; 172 (02) 466-469
• 143 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
• 144 Carreras A, Zhang SX, Peris E. et al. Chronic sleep fragmentation induces endothelial dysfunction and structural vascular changes in mice. Sleep 2014; 37 (11) 1817-1824
• 145 May AM, Mehra R. Obstructive sleep apnea: role of intermittent hypoxia and inflammation. Semin Respir Crit Care Med 2014; 35 (05) 531-544
• 146 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
• 147 Gosselin N, Baril AA, Osorio RS, Kaminska M, Carrier J. Obstructive sleep apnea and the risk of cognitive decline in older adults. Am J Respir Crit Care Med 2019; 199 (02) 142-148
• 148 Pase MP, Harrison S, Misialek JR. et al. Sleep architecture, obstructive sleep apnea, and cognitive function in adults. JAMA Netw Open 2023; 6 (07) e2325152
• 149 Narkiewicz K, Montano N, Cogliati C, van de Borne PJ, Dyken ME, Somers VK. Altered cardiovascular variability in obstructive sleep apnea. Circulation 1998; 98 (11) 1071-1077
• 150 Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without obstructive sleep apnea. Circulation 1998; 98 (08) 772-776
• 151 Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand 2003; 177 (03) 385-390
• 152 Santisteban MM, Iadecola C, Carnevale D. Hypertension, neurovascular dysfunction, and cognitive impairment. Hypertension 2023; 80 (01) 22-34
• 153 Hermann DM, Bassetti CL. Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery. Neurology 2016; 87 (13) 1407-1416
• 154 Turner KL, Gheres KW, Proctor EA, Drew PJ. Neurovascular coupling and bilateral connectivity during NREM and REM sleep. eLife 2020; 9: 9
• 155 Zhang D, Ruan J, Peng S. et al. Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling. Nat Neurosci 2024; 27 (02) 232-248
• 156 Betta M, Handjaras G, Leo A. et al. Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep. Neuroimage 2021; 236: 118117
• 157 Phillips AA, Chan FH, Zheng MM, Krassioukov AV, Ainslie PN. Neurovascular coupling in humans: physiology, methodological advances and clinical implications. J Cereb Blood Flow Metab 2016; 36 (04) 647-664
• 158 Christou K, Markoulis N, Moulas AN, Pastaka C, Gourgoulianis KI. Reactive oxygen metabolites (ROMs) as an index of oxidative stress in obstructive sleep apnea patients. Sleep Breath 2003; 7 (03) 105-110
• 159 Trivedi MS, Holger D, Bui AT, Craddock TJA, Tartar JL. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status. PLoS One 2017; 12 (07) e0181978
• 160 Everson CA, Henchen CJ, Szabo A, Hogg N. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats. Sleep 2014; 37 (12) 1929-1940
• 161 Snyder B, Shell B, Cunningham JT, Cunningham RL. Chronic intermittent hypoxia induces oxidative stress and inflammation in brain regions associated with early-stage neurodegeneration. Physiol Rep 2017; 5 (09) 5
• 162 Deurveilher S, Golovin T, Hall S, Semba K. Microglia dynamics in sleep/wake states and in response to sleep loss. Neurochem Int 2021; 143: 104944
• 163 Wisor JP, Schmidt MA, Clegern WC. Evidence for neuroinflammatory and microglial changes in the cerebral response to sleep loss. Sleep 2011; 34 (03) 261-272
• 164 Zhang YM, Wei RM, Feng YZ. et al. Sleep deprivation aggravates lipopolysaccharide-induced anxiety, depression and cognitive impairment: the role of pro-inflammatory cytokines and synaptic plasticity-associated proteins. J Neuroimmunol 2024; 386: 578252
• 165 Izumi Y, Cashikar AG, Krishnan K. et al. A proinflammatory stimulus disrupts hippocampal plasticity and learning via microglial activation and 25-hydroxycholesterol. J Neurosci 2021; 41 (49) 10054-10064
• 166 Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14 (06) 540-545
• 167 Buysse DJ, Reynolds III CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28 (02) 193-213
• 168 Chung F, Yegneswaran B, Liao P. et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008; 108 (05) 812-821
• 169 Amiri S, Hasani J, Satkin M. Effect of exercise training on improving sleep disturbances: a systematic review and meta-analysis of randomized control trials. Sleep Med 2021; 84: 205-218
• 170 Edinger JD, Arnedt JT, Bertisch SM. et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2021; 17 (02) 255-262
• 171 Panel AGSBCUE. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2023; 71 (07) 2052-2081
• 172 Morin CM, Buysse DJ. Management of insomnia. N Engl J Med 2024; 391 (03) 247-258
• 173 Herring WJ, Ceesay P, Snyder E. et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial. Alzheimers Dement 2020; 16 (03) 541-551
• 174 Lucey BP, Liu H, Toedebusch CD. et al. Suvorexant acutely decreases tau phosphorylation and Aβ in the human CNS. Ann Neurol 2023; 94 (01) 27-40
• 175 Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG. Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med 2019; 15 (02) 335-343
• 176 Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev 2011; 15 (06) 343-356
• 177 Guo MY, Li PJ, Xiao Y, Cao Y, Liang ZA. Effectiveness of mandibular advancement devices in the treatment of obstructive sleep apnea and the impact of different body positions on treatment: a systematic review and meta-analysis. Sleep Med 2024; 113: 275-283
• 178 Abid R, Zhang L, Bhat A. Non-CPAP therapies for obstructive sleep apnea in adults. Mo Med 2024; 121 (05) 385-390
• 179 Malhotra A, Grunstein RR, Fietze I. et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024; 391 (13) 1193-1205
• 180 Patel RM, Wang HZ, Jamro EL. et al. Response to hypoglossal nerve stimulation changes with body mass index and supine sleep. JAMA Otolaryngol Head Neck Surg 2024; 150 (05) 421-428
• 181 Strollo Jr PJ, Soose RJ, Maurer JT. et al; STAR Trial Group. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med 2014; 370 (02) 139-149
• 182 Winkelman JW, Berkowski JA, DelRosso LM. et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2025; 21 (01) 137-152
• 183 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 (04) 759-768
• 184 Livingston G, Huntley J, Liu KY. et al. Dementia prevention, intervention, and care: 2024 report of the Lancet Standing Commission. Lancet 2024; 404 (10452): 572-628
• 185 Castillo PR. Clinical neurobiology of sleep and wakefulness. Continuum (Minneap Minn) 2023; 29 (04) 1016-1030