Current Sleep Medicine Reports

, Volume 5, Issue 1, pp 1–12 | Cite as

A Human Neuroimaging Perspective on Sleep in Normative and Pathological Ageing

  • Nathan CrossEmail author
  • Nadia Gosselin
  • Thien Thanh Dang-VuEmail author
Sleep and Aging (A Spira, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Sleep and Aging


Purpose of Review

There is a growing body of evidence detailing how phenotypic changes in sleep with increasing age are not only associated with declining functions, but how sleep disorders may also indicate underlying pathology, particularly neurodegenerative diseases. As sleep is implicated in maintenance and protective processes within the brain, poor sleep quality may also contribute to neurodegenerative processes. This review details the neuroimaging literature surrounding age-related changes in sleep and outlines how sleep disorders are related to changes in neural integrity with advancing age.

Recent Findings

Sleep disturbance can increase the production of amyloid-β, an age-related peptide associated with Alzheimer’s disease pathology. Obstructive sleep apnoea has been implicated in exacerbating both changes that occur with both normative ageing and neurodegenerative processes in dementia. While conversion rates may differ, recent evidence suggests all patients with REM sleep behaviour disorder may eventually develop an α-synucleinopathy-related neurodegenerative disease.


Sleep is a complex behaviour and encapsulates many important processes for overall brain health. The relationship between changing features of sleep with age and neurodegeneration is highly complicated; however, human neuroimaging research provides great potential to understand these multifaceted connections.


Sleep disorders Insomnia Obstructive sleep apnoea REM sleep behaviour disorder Neurodegenerative disease Dementia 


Compliance with Ethical Standards

Conflict of Interest

Nathan Cross, Nadia Gosselin and Thien-Thanh Dang-Vu each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Tononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014;81(1):12–34.Google Scholar
  2. 2.
    Born J, Wilhelm I. System consolidation of memory during sleep. Psychol Res. 2012;76(2):192–203.Google Scholar
  3. 3.
    Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science (New York, NY). 2013;342(6156):373–7.Google Scholar
  4. 4.
    Mander BA, Winer JR, Walker MP. Sleep and human aging. Neuron. 2017;94(1):19–36.Google Scholar
  5. 5.
    Scullin MK. Do older adults need sleep? A review of neuroimaging, sleep, and aging studies. Curr Sleep Med Rep. 2017;3(3):204–14.Google Scholar
  6. 6.
    Uchida S, Shioda K, Morita Y, Kubota C, Ganeko M, Takeda N. Exercise effects on sleep physiology. Front Neurol. 2012;3:48.Google Scholar
  7. 7.
    Carrier J, Bliwise D. Sleep and circadian rhythms in normal aging. In: Billiard M, editor. Sleep: physiology, investigations, and medicine. Boston, MA: Springer US; 2003. p. 297–332.Google Scholar
  8. 8.
    Gaudreau H, Carrier J, Montplaisir J. Age-related modifications of NREM sleep EEG: from childhood to middle age. J Sleep Res. 2001;10(3):165–72.Google Scholar
  9. 9.
    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(7):861–8.Google Scholar
  10. 10.
    Carrier J, Land S, Buysse DJ, Kupfer DJ, Monk TH. The effects of age and gender on sleep EEG power spectral density in the middle years of life (ages 20-60 years old). Psychophysiology. 2001;38(2):232–42.Google Scholar
  11. 11.
    Mourtazaev MS, Kemp B, Zwinderman AH, Kamphuisen HA. Age and gender affect different characteristics of slow waves in the sleep EEG. Sleep. 1995;18(7):557–64.Google Scholar
  12. 12.
    Martin N, Lafortune M, Godbout J, Barakat M, Robillard R, Poirier G, et al. Topography of age-related changes in sleep spindles. Neurobiol Aging. 2013;34(2):468–76.Google Scholar
  13. 13.
    Clawson BC, Durkin J, Aton SJ. Form and function of sleep spindles across the lifespan. Neural Plast. 2016;2016:6936381.Google Scholar
  14. 14.
    Crowley K, Trinder J, Kim Y, Carrington M, Colrain IM. The effects of normal aging on sleep spindle and K-complex production. Clin Neurophysiol. 2002;113(10):1615–22.Google Scholar
  15. 15.
    • Spira AP, Gonzalez CE, Venkatraman VK, Wu MN, Pacheco J, Simonsick EM, et al. Sleep duration and subsequent cortical thinning in cognitively Normal older adults. Sleep. 2016;39(5):1121–8 This study provides evidence that subjective short and long sleep duration predicts decreased cortical thickness in frontal and temporal areas of the brain.Google Scholar
  16. 16.
    Moscovitch M, Winocur G. Frontal lobes, memory, and aging. Ann N Y Acad Sci. 1995;769:119–50.Google Scholar
  17. 17.
    West RL. An application of prefrontal cortex function theory to cognitive aging. Psychol Bull. 1996;120(2):272–92.Google Scholar
  18. 18.
    Gildner TE, Liebert MA, Kowal P, Chatterji S, Snodgrass JJ. Associations between sleep duration, sleep quality, and cognitive test performance among older adults from six middle income countries: results from the study on global ageing and adult health (SAGE). J Clin Sleep Med. 2014;10(6):613–21.Google Scholar
  19. 19.
    Bliwise DL, Young TB. The parable of parabola: what the U-shaped curve can and cannot tell us about sleep. Sleep. 2007;30(12):1614–5.Google Scholar
  20. 20.
    Weber M, Webb CA, Deldonno SR, Kipman M, Schwab ZJ, Weiner MR, et al. Habitual ‘sleep credit’ is associated with greater grey matter volume of the medial prefrontal cortex, higher emotional intelligence and better mental health. J Sleep Res. 2013;22(5):527–34.Google Scholar
  21. 21.
    Yaffe K, Nasrallah I, Hoang TD, Lauderdale DS, Knutson KL, Carnethon MR, et al. Sleep duration and white matter quality in middle-aged adults. Sleep. 2016;39(9):1743–7.Google Scholar
  22. 22.
    Dijk DJ, Beersma DGM, van den Hoofdakker RH. All night spectral analysis of EEG sleep in young adult and middle-aged male subjects. Neurobiol Aging. 1989;10(6):677–82.Google Scholar
  23. 23.
    Landolt H-P, Borbély AA. Age-dependent changes in sleep EEG topography. Clin Neurophysiol. 2001;112(2):369–77.Google Scholar
  24. 24.
    Landolt H-P, Dijk D-J, Achermann P, Borbély AA. Effect of age on the sleep EEG: slow-wave activity and spindle frequency activity in young and middle-aged men. Brain Res. 1996;738(2):205–12.Google Scholar
  25. 25.
    Mander BA, Rao V, Lu B, Saletin JM, Lindquist JR, Ancoli-Israel S, et al. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci. 2013;16(3):357–64.Google Scholar
  26. 26.
    Mander BA, Marks SM, Vogel JW, Rao V, Lu B, Saletin JM, et al. Beta-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci. 2015;18(7):1051–7.Google Scholar
  27. 27.
    Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056.Google Scholar
  28. 28.
    • Fogel S, Vien C, Karni A, Benali H, Carrier J, Doyon J. Sleep spindles: a physiological marker of age-related changes in gray matter in brain regions supporting motor skill memory consolidation. Neurobiology of aging. 2017;49:154–64 This study provides evidence that the relationship between sleep spindles and cortical grey matter is different for young and old subjects.Google Scholar
  29. 29.
    • Gaudreault PO, Gosselin N, Lafortune M, Deslauriers-Gauthier S, Martin N, Bouchard M, et al. The association between white matter and sleep spindles differs in young and older individuals. Sleep. 2018;41(9) This study provides evidence that the relationship between sleep spindles and thalamocortical white matter tracts is different for young and old subjects.Google Scholar
  30. 30.
    Sexton CE, Storsve AB, Walhovd KB, Johansen-Berg H, Fjell AM. Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults. Neurology. 2014;83(11):967–73.Google Scholar
  31. 31.
    Branger P, Arenaza-Urquijo EM, Tomadesso C, Mezenge F, Andre C, de Flores R, et al. Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood. Neurobiol Aging. 2016;41:107–14.Google Scholar
  32. 32.
    Lim AS, Fleischman DA, Dawe RJ, Yu L, Arfanakis K, Buchman AS, et al. Regional neocortical gray matter structure and sleep fragmentation in older adults. Sleep. 2016;39(1):227–35.Google Scholar
  33. 33.
    Brown BM, Rainey-Smith SR, Villemagne VL, Weinborn M, Bucks RS, Sohrabi HR, et al. The relationship between sleep quality and brain amyloid burden. Sleep. 2016;39(5):1063–8.Google Scholar
  34. 34.
    Sprecher KE, Koscik RL, Carlsson CM, Zetterberg H, Blennow K, Okonkwo OC, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017;89(5):445–53.Google Scholar
  35. 35.
    •• Lucey BP, Hicks TJ, McLeland JS, Toedebusch CD, Boyd J, Elbert DL, et al. Effect of sleep on overnight cerebrospinal fluid amyloid beta kinetics. Ann Neurol. 2018;83(1):197–204 This study provides evidence that one night of sleep deprivation results in increased levels of Aβ in the cerebrospinal fluid.Google Scholar
  36. 36.
    •• Ju YE, Ooms S, Sutphen C, Macauley S, Zangrilli M, Jerome G, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain. 2017;(0):1–8 This study provides evidence that one night of disruption to slow wave sleep specifically results in increased levels of Aβ in the cerebrospinal fluid.Google Scholar
  37. 37.
    Vlassenko AG, Vaishnavi SN, Couture L, Sacco D, Shannon BJ, Mach RH, et al. Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition. Proc Natl Acad Sci. 2010;107(41):17763–7.Google Scholar
  38. 38.
    Cross NE, Lagopoulos J, Duffy SL, Cockayne NL, Hickie IB, Lewis SJ, et al. Sleep quality in healthy older people: relationship with (1) H magnetic resonance spectroscopy markers of glial and neuronal integrity. Behav Neurosci. 2013;127(5):803–10.Google Scholar
  39. 39.
    Lim AS, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA. Modification of the relationship of the apolipoprotein E epsilon4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA neurology. 2013;70(12):1544–51.Google Scholar
  40. 40.
    Lim AS, Kowgier M, Yu L, Buchman AS, Bennett DA. Sleep fragmentation and the risk of incident Alzheimer’s disease and cognitive decline in older persons. Sleep. 2013;36(7):1027–32.Google Scholar
  41. 41.
    Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. Sleep. 2014;37(7):1171–8.Google Scholar
  42. 42.
    Chou YY, Lepore N, Avedissian C, Madsen SK, Parikshak N, Hua X, et al. Mapping correlations between ventricular expansion and CSF amyloid and tau biomarkers in 240 subjects with Alzheimer’s disease, mild cognitive impairment and elderly controls. NeuroImage. 2009;46(2):394–410.Google Scholar
  43. 43.
    Porter VR, Buxton WG, Avidan AY. Sleep, cognition and dementia. Curr Psychiatry Rep. 2015;17(12):97.Google Scholar
  44. 44.
    Urrestarazu E, Iriarte J. Clinical management of sleep disturbances in Alzheimer’s disease: current and emerging strategies. Nat Sci Sleep. 2016;8:21–33.Google Scholar
  45. 45.
    McKinnon A, Terpening Z, Hickie IB, Batchelor J, Grunstein R, Lewis SJ, et al. Prevalence and predictors of poor sleep quality in mild cognitive impairment. J Geriatr Psychiatry Neurol. 2014;27(3):204–11.Google Scholar
  46. 46.
    Naismith SL, Rogers NL, Hickie IB, Mackenzie J, Norrie LM, Lewis SJ. Sleep well, think well: sleep-wake disturbance in mild cognitive impairment. J Geriatr Psychiatry Neurol. 2010;23(2):123–30.Google Scholar
  47. 47.
    Miyata S, Noda A, Iwamoto K, Kawano N, Okuda M, Ozaki N. Poor sleep quality impairs cognitive performance in older adults. J Sleep Res. 2013;22(5):535–41.Google Scholar
  48. 48.
    American PA. Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric A, American Psychiatric Association DSMTF, editors. Arlington, VA: American Psychiatric Association; 2013.Google Scholar
  49. 49.
    Crowley K. Sleep and sleep disorders in older adults. Neuropsychol Rev. 2011;21(1):41–53.Google Scholar
  50. 50.
    Foley D, Ancoli-Israel S, Britz P, Walsh J. Sleep disturbances and chronic disease in older adults: results of the 2003 National Sleep Foundation sleep in America survey. J Psychosom Res. 2004;56(5):497–502.Google Scholar
  51. 51.
    Vitiello MV, Larsen LH, Moe KE. Age-related sleep change: gender and estrogen effects on the subjective-objective sleep quality relationships of healthy, noncomplaining older men and women. J Psychosom Res. 2004;56(5):503–10.Google Scholar
  52. 52.
    Liu X, Liu L. Sleep habits and insomnia in a sample of elderly persons in China. Sleep. 2005;28(12):1579–87.Google Scholar
  53. 53.
    Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002;6(2):97–111.Google Scholar
  54. 54.
    Blackwell T, Yaffe K, Laffan A, Ancoli-Israel S, Redline S, Ensrud KE, et al. Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study. Sleep. 2014;37(4):655–63.Google Scholar
  55. 55.
    Hahn EA, Wang HX, Andel R, Fratiglioni L. A change in sleep pattern may predict Alzheimer disease. Am J Geriatr Psychiatry. 2014;22(11):1262–71.Google Scholar
  56. 56.
    Sterniczuk R, Theou O, Rusak B, Rockwood K. Sleep disturbance is associated with incident dementia and mortality. Curr Alzheimer Res. 2013;10(7):767–75.Google Scholar
  57. 57.
    Virta JJ, Heikkila K, Perola M, Koskenvuo M, Raiha I, Rinne JO, et al. Midlife sleep characteristics associated with late life cognitive function. Sleep. 2013;36(10):1533–41.41a.Google Scholar
  58. 58.
    de Almondes KM, Costa MV, Malloy-Diniz LF, Diniz BS. Insomnia and risk of dementia in older adults: systematic review and meta-analysis. J Psychiatr Res. 2016;77:109–15.Google Scholar
  59. 59.
    Spira AP, Chen-Edinboro LP, Wu MN, Yaffe K. Impact of sleep on the risk of cognitive decline and dementia. Curr Opin Psychiatry. 2014;27(6):478–83.Google Scholar
  60. 60.
    Chen PL, Lee WJ, Sun WZ, Oyang YJ, Fuh JL. Risk of dementia in patients with insomnia and long-term use of hypnotics: a population-based retrospective cohort study. PLoS One. 2012;7(11):e49113.Google Scholar
  61. 61.
    Montgomery P, Dennis J. A systematic review of non-pharmacological therapies for sleep problems in later life. Sleep Med Rev. 2004;8(1):47–62.Google Scholar
  62. 62.
    Valkanova V, Ebmeier KP, Allan CL. Depression is linked to dementia in older adults. Practitioner. 2017;261(1800):11–5.Google Scholar
  63. 63.
    Naismith SL, Rogers NL, Lewis SJ, Diamond K, Terpening Z, Norrie L, et al. Sleep disturbance in mild cognitive impairment: differential effects of current and remitted depression. Acta Neuropsychiatr. 2011;23(4):167–72.Google Scholar
  64. 64.
    Naismith SL, Rogers NL, Lewis SJ, Terpening Z, Ip T, Diamond K, et al. Sleep disturbance relates to neuropsychological functioning in late-life depression. J Affect Disord. 2011;132(1–2):139–45.Google Scholar
  65. 65.
    Winkelman JW, Benson KL, Buxton OM, Lyoo IK, Yoon S, O'Connor S, et al. Lack of hippocampal volume differences in primary insomnia and good sleeper controls: an MRI volumetric study at 3 Tesla. Sleep Med. 2010;11(6):576–82.Google Scholar
  66. 66.
    Noh HJ, Joo EY, Kim ST, Yoon SM, Koo DL, Kim D, et al. The relationship between hippocampal volume and cognition in patients with chronic primary insomnia. J Clin Neurol (Seoul, Korea). 2012;8(2):130–8.Google Scholar
  67. 67.
    Joo EY, Kim SH, Kim ST, Hong SB. Hippocampal volume and memory in narcoleptics with cataplexy. Sleep Med. 2012;13(4):396–401.Google Scholar
  68. 68.
    Spiegelhalder K, Regen W, Baglioni C, Kloppel S, Abdulkadir A, Hennig J, et al. Insomnia does not appear to be associated with substantial structural brain changes. Sleep. 2013;36(5):731–7.Google Scholar
  69. 69.
    Winkelman JW, Plante DT, Schoerning L, Benson K, Buxton OM, O'Connor SP, et al. Increased rostral anterior cingulate cortex volume in chronic primary insomnia. Sleep. 2013;36(7):991–8.Google Scholar
  70. 70.
    Koo DL, Shin JH, Lim JS, Seong JK, Joo EY. Changes in subcortical shape and cognitive function in patients with chronic insomnia. Sleep Med. 2017;35:23–6.Google Scholar
  71. 71.
    Altena E, Vrenken H, Van Der Werf YD, van den Heuvel OA, Van Someren EJ. Reduced orbitofrontal and parietal gray matter in chronic insomnia: a voxel-based morphometric study. Biol Psychiatry. 2010;67(2):182–5.Google Scholar
  72. 72.
    Altena E, Van Der Werf YD, Sanz-Arigita EJ, Voorn TA, Rombouts SA, Kuijer JP, et al. Prefrontal hypoactivation and recovery in insomnia. Sleep. 2008;31(9):1271–6.Google Scholar
  73. 73.
    American Academy of Sleep Medicine. International classification of sleep disorders, revised: diagnostic and coding manual. Chicago, Illinois: American Academy of Sleep Medicine; 2001.Google Scholar
  74. 74.
    Romero-Corral A, Caples SM, Lopez-Jimenez F, Somers VK. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest. 2010;137(3):711–9.Google Scholar
  75. 75.
    Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men: I. prevalence and severity. Am J Respir Crit Care Med. 1998;157(1):144–8.Google Scholar
  76. 76.
    Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3(4):310–8.Google Scholar
  77. 77.
    Launois SH, Pepin JL, Levy P. Sleep apnea in the elderly: a specific entity? Sleep Med Rev. 2007;11(2):87–97.Google Scholar
  78. 78.
    Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive sleep apnea syndrome in the Sao Paulo epidemiologic sleep study. Sleep Med. 2010;11(5):441–6.Google Scholar
  79. 79.
    Castronovo V, Canessa N, Strambi LF, Aloia MS, Consonni M, Marelli S, et al. Brain activation changes before and after PAP treatment in obstructive sleep apnea. Sleep. 2009;32(9):1161–72.Google Scholar
  80. 80.
    • Kim H, Joo E, Suh S, Kim J-H, Kim ST, Hong SB. Effects of long-term treatment on brain volume in patients with obstructive sleep apnea syndrome. Hum Brain Mapp. 2016;37(1):395–409 This study provides evidence that revealed the positive effects of long-term CPAP treatment on brain structure in patients with OSA.Google Scholar
  81. 81.
    Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW. Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep. 1986;9(2):293–308.Google Scholar
  82. 82.
    Osorio RS, Gumb T, Pirraglia E, Varga AW, Lu SE, Lim J, et al. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology. 2015;84(19):1964–71.Google Scholar
  83. 83.
    Boesch SM, Frauscher B, Brandauer E, Wenning GK, Hogl B, Poewe W. Disturbance of rapid eye movement sleep in spinocerebellar ataxia type 2. Mov Disord. 2006;21(10):1751–4.Google Scholar
  84. 84.
    Schenck CH, Mahowald MW, Kim SW, O'Connor KA, Hurwitz TD. Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep. 1992;15(3):226–35.Google Scholar
  85. 85.
    Xi Z, Luning W. REM sleep behavior disorder in a patient with pontine stroke. Sleep Med. 2009;10(1):143–6.Google Scholar
  86. 86.
    Fantini ML, Ferini-Strambi L, Montplaisir J. Idiopathic REM sleep behavior disorder: toward a better nosologic definition. Neurology. 2005;64(5):780–6.Google Scholar
  87. 87.
    Senaratna CV, Perret JL, Lodge CJ, Lowe AJ, Campbell BE, Matheson MC, et al. Prevalence of obstructive sleep apnea in the general population: a systematic review. Sleep Med Rev. 2017;34:70–81.Google Scholar
  88. 88.
    Edwards BA, O'Driscoll DM, Ali A, Jordan AS, Trinder J, Malhotra A. Aging and sleep: physiology and pathophysiology. Semin Respir Crit Care Med. 2010;31(5):618–33.Google Scholar
  89. 89.
    Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet (London, England). 2005;365(9464):1046–53.Google Scholar
  90. 90.
    Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J. Sleep apnea and hypertension. A population-based study. Ann Intern Med. 1994;120(5):382–8.Google Scholar
  91. 91.
    Zhang W, Liang-yi S. Obstructive sleep apnea syndrome (OSAS) and hypertension: pathogenic mechanisms and possible therapeutic approaches. Ups J Med Sci. 2012;117(4):370–82.Google Scholar
  92. 92.
    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):1447–51.Google Scholar
  93. 93.
    Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O'Connor GT, Resnick HE, et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med. 2010;182(2):269–77.Google Scholar
  94. 94.
    Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J. 2004;25(9):735–41.Google Scholar
  95. 95.
    Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: the Busselton health study. Sleep. 2008;31(8):1079–85.Google Scholar
  96. 96.
    Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farre R. Sleep-disordered breathing and cancer mortality: results from the Wisconsin sleep cohort study. Am J Respir Crit Care Med. 2012;186(2):190–4.Google Scholar
  97. 97.
    Cross N, Lampit A, Pye J, Grunstein RR, Marshall N, Naismith SL. Is obstructive sleep apnoea related to neuropsychological function in healthy older adults? A systematic review and meta-analysis. Neuropsychol Rev. 2017;27:389–402.Google Scholar
  98. 98.
    Harada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clin Geriatr Med. 2013;29(4):737–52.Google Scholar
  99. 99.
    Salthouse TA. Selective review of cognitive aging. J Int Neuropsychol Soc. 2010;16(5):754–60.Google Scholar
  100. 100.
    Ayalon L, Ancoli-Israel S, Klemfuss Z, Shalauta MD, Drummond SP. Increased brain activation during verbal learning in obstructive sleep apnea. NeuroImage. 2006;31(4):1817–25.Google Scholar
  101. 101.
    Cabeza R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging. 2002;17(1):85–100.Google Scholar
  102. 102.
    Morcom AM, Good CD, Frackowiak RS, Rugg MD. Age effects on the neural correlates of successful memory encoding. Brain. 2003;126(Pt 1):213–29.Google Scholar
  103. 103.
    Ayalon L, Ancoli-Israel S, Drummond SP. Obstructive sleep apnea and age: a double insult to brain function? Am J Respir Crit Care Med. 2010;182(3):413–9.Google Scholar
  104. 104.
    Chang WP, Liu ME, Chang WC, Yang AC, Ku YC, Pai JT, et al. Sleep apnea and the risk of dementia: a population-based 5-year follow-up study in Taiwan. PLoS One. 2013;8(10):e78655.Google Scholar
  105. 105.
    Yaffe K, Laffan AM, Harrison SL, Redline S, Spira AP, Ensrud KE, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011;306(6):613–9.Google Scholar
  106. 106.
    Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Sleep-disordered breathing in community-dwelling elderly. Sleep. 1991;14(6):486–95.Google Scholar
  107. 107.
    Emamian F, Khazaie H, Tahmasian M, Leschziner GD, Morrell MJ, Hsiung G-YR, et al. The association between obstructive sleep apnea and Alzheimer’s disease: a meta-analysis perspective. Front Aging Neurosci. 2016;8:78.Google Scholar
  108. 108.
    Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.Google Scholar
  109. 109.
    Canessa N, Castronovo V, Cappa SF, Aloia MS, Marelli S, Falini A, et al. Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am J Respir Crit Care Med. 2011;183(10):1419–26.Google Scholar
  110. 110.
    Macey PM, Haris N, Kumar R, Thomas MA, Woo MA, Harper RM. Obstructive sleep apnea and cortical thickness in females and males. PLoS One. 2018;13(3):e0193854.Google Scholar
  111. 111.
    Morrell MJ, McRobbie DW, Quest RA, Cummin AR, Ghiassi R, Corfield DR. Changes in brain morphology associated with obstructive sleep apnea. Sleep Med. 2003;4(5):451–4.Google Scholar
  112. 112.
    Torelli F, Moscufo N, Garreffa G, Placidi F, Romigi A, Zannino S, et al. Cognitive profile and brain morphological changes in obstructive sleep apnea. NeuroImage. 2011;54(2):787–93.Google Scholar
  113. 113.
    Weng HH, Tsai YH, Chen CF, Lin YC, Yang CT, Tsai YH, et al. Mapping gray matter reductions in obstructive sleep apnea: an activation likelihood estimation meta-analysis. Sleep. 2014;37(1):167–75.Google Scholar
  114. 114.
    Yaouhi K, Bertran F, Clochon P, Mezenge F, Denise P, Foret J, et al. A combined neuropsychological and brain imaging study of obstructive sleep apnea. J Sleep Res. 2009;18(1):36–48.Google Scholar
  115. 115.
    •• Baril AA, Gagnon K, Brayet P, Montplaisir J, De Beaumont L, Carrier J, et al. Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults. Am J Respir Crit Care Med. 2017;195(11):1509–18 This study provides evidence that OSA is associated with increased cortical thickness in healthy and older middle-aged adults, suggestive of reactive or maladaptive processes.Google Scholar
  116. 116.
    Celle S, Peyron R, Faillenot I, Pichot V, Alabdullah M, Gaspoz JM, et al. Undiagnosed sleep-related breathing disorders are associated with focal brainstem atrophy in the elderly. Hum Brain Mapp. 2009;30(7):2090–7.Google Scholar
  117. 117.
    •• Cross NE, Memarian N, Duffy SL, Paquola C, LaMonica H, D'Rozario A, et al. Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia. Eur Respir J. 2018;52(1) This study provides evidence that OSA is associated with increased thickness in some cortical areas, and decreased thickness in the temporal cortices, in older middle-aged adults with subjective and objective cognitive impairment.Google Scholar
  118. 118.
    •• Boucetta S, Salimi A, Dadar M, Jones BE, Collins DL, Dang-Vu TT. Structural brain alterations associated with rapid eye movement sleep behavior disorder in Parkinson’s disease. Sci Report. 2016;6:26782 This study provides evidence of extensive structural abnormalities associated with RBD in Parkinson’s disease, which prominently involved volume decreases in the pontomesencephalic tegmentum, supporting a consistent loss of neurons in this region with RBD.Google Scholar
  119. 119.
    Duffy SL, Lagopoulos J, Terpening Z, Lewis SJ, Grunstein R, Mowszowski L, et al. Association of anterior cingulate glutathione with sleep apnea in older adults at-risk for dementia. Sleep. 2016;39(4):899–906.Google Scholar
  120. 120.
    Rosenzweig I, Williams SC, Morrell MJ. The impact of sleep and hypoxia on the brain: potential mechanisms for the effects of obstructive sleep apnea. Curr Opin Pulm Med. 2014;20(6):565–71.Google Scholar
  121. 121.
    Rostanski SK, Zimmerman ME, Schupf N, Manly JJ, Westwood AJ, Brickman AM, et al. Sleep disordered breathing and white matter hyperintensities in community-dwelling elders. Sleep. 2016;39(4):785–91.Google Scholar
  122. 122.
    Gomez-Choco MJ, Iranzo A, Blanco Y, Graus F, Santamaria J, Saiz A. Prevalence of restless legs syndrome and REM sleep behavior disorder in multiple sclerosis. Multiple sclerosis. Houndmills, Basingstoke, England. 2007;13(6):805–8.Google Scholar
  123. 123.
    Plazzi G, Corsini R, Provini F, Pierangeli G, Martinelli P, Montagna P, et al. REM sleep behavior disorders in multiple system atrophy. Neurology. 1997;48(4):1094–7.Google Scholar
  124. 124.
    Zhang X, Sun X, Wang J, Tang L, Xie A. Prevalence of rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease: a meta and meta-regression analysis. Neurol Sci. 2017;38(1):163–70.Google Scholar
  125. 125.
    Boeve BF, Silber MH, Ferman TJ, Kokmen E, Smith GE, Ivnik RJ, et al. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology. 1998;51(2):363–70.Google Scholar
  126. 126.
    McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology. 2017;89(1):88–100.Google Scholar
  127. 127.
    Postuma RB, Gagnon JF, Montplaisir JY. REM sleep behavior disorder: from dreams to neurodegeneration. Neurobiol Dis. 2012;46(3):553–8.Google Scholar
  128. 128.
    Boot BP, Boeve BF, Roberts RO, Ferman TJ, Geda YE, Pankratz VS, et al. Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study. Ann Neurol. 2012;71(1):49–56.Google Scholar
  129. 129.
    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):1296–300.Google Scholar
  130. 130.
    Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12(5):443–53.Google Scholar
  131. 131..
    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(8):744–8.Google Scholar
  132. 132.
    Boeve BF, Silber MH, Ferman TJ, Lin SC, Benarroch EE, Schmeichel AM, 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(8):754–62.Google Scholar
  133. 133.
    Vilas D, Iranzo A, Tolosa E, Aldecoa I, Berenguer J, Vilaseca I, et al. Assessment of alpha-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2016;15(7):708–18.Google Scholar
  134. 134.
    Postuma RB, Gagnon JF, Montplaisir J. Clinical prediction of Parkinson’s disease: planning for the age of neuroprotection. J Neurol Neurosurg Psychiatry. 2010;81(9):1008–13.Google Scholar
  135. 135.
    Siegel JM, Tobler I. Mammalian sleep. Principles and Practice of Sleep Medicine. 42005. p. 91–100.Google Scholar
  136. 136.
    Weber F, Chung S, Beier KT, Xu M, Luo L, Dan Y. Control of REM sleep by ventral medulla GABAergic neurons. Nature. 2015;526(7573):435–8.Google Scholar
  137. 137.
    Magoun HW, Rhines R. An inhibitory mechanism in the bulbar reticular formation. J Neurophysiol. 1946;9:165–71.Google Scholar
  138. 138.
    Schenkel E, Siegel JM. REM sleep without atonia after lesions of the medial medulla. Neurosci Lett. 1989;98(2):159–65.Google Scholar
  139. 139.
    Knudsen S, Gammeltoft S, Jennum PJ. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency. Brain J Neurol. 2010;133(Pt 2):568–79.Google Scholar
  140. 140.
    Kajimura N, Uchiyama M, Takayama Y, Uchida S, Uema T, Kato M, et al. Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep. J Neurosci. 1999;19(22):10065–73.Google Scholar
  141. 141.
    Maquet P, Peters J, Aerts J, Delfiore G, Degueldre C, Luxen A, et al. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature. 1996;383(6596):163–6.Google Scholar
  142. 142.
    Hendricks JC, Morrison AR, Mann GL. Different behaviors during paradoxical sleep without atonia depend on pontine lesion site. Brain Res. 1982;239(1):81–105.Google Scholar
  143. 143.
    Sakai K, Sastre JP, Salvert D, Touret M, Tohyama M, Jouvet M. Tegmentoreticular projections with special reference to the muscular atonia during paradoxical sleep in the cat: an HRP study. Brain Res. 1979;176(2):233–54.Google Scholar
  144. 144.
    Scherfler C, Frauscher B, Schocke M, Iranzo A, Gschliesser V, Seppi K, et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol. 2011;69(2):400–7.Google Scholar
  145. 145.
    Unger MM, Belke M, Menzler K, Heverhagen JT, Keil B, Stiasny-Kolster K, et al. Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep. 2010;33(6):767–73.Google Scholar
  146. 146.
    Hanyu H, Inoue Y, Sakurai H, Kanetaka H, Nakamura M, Miyamoto T, et al. Voxel-based magnetic resonance imaging study of structural brain changes in patients with idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord. 2012;18(2):136–9.Google Scholar
  147. 147.
    Rahayel S, Montplaisir J, Monchi O, Bedetti C, Postuma RB, Brambati S, et al. Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2015;30(5):680–7.Google Scholar
  148. 148.
    Ford AH, Duncan GW, Firbank MJ, Yarnall AJ, Khoo TK, Burn DJ, et al. Rapid eye movement sleep behavior disorder in Parkinson's disease: magnetic resonance imaging study. Mov Disord. 2013;28(6):832–6.Google Scholar
  149. 149.
    Garcia-Lorenzo D, Longo-Dos Santos C, Ewenczyk C, Leu-Semenescu S, Gallea C, Quattrocchi G, et al. The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson's disease. Brain J Neurol. 2013;136(Pt 7):2120–9.Google Scholar
  150. 150.
    Salsone M, Cerasa A, Arabia G, Morelli M, Gambardella A, Mumoli L, et al. Reduced thalamic volume in Parkinson disease with REM sleep behavior disorder: volumetric study. Parkinsonism Relat Disord. 2014;20(9):1004–8.Google Scholar
  151. 151.
    Dauvilliers Y, Boudousq V, Lopez R, Gabelle A, De Cock VC, Bayard S, et al. Increased perfusion in supplementary motor area during a REM sleep behaviour episode. Sleep Med. 2011;12(5):531–2.Google Scholar
  152. 152.
    Kim YK, Yoon IY, Kim JM, Jeong SH, Kim KW, Shin YK, et al. The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder. Eur J Neurol. 2010;17(3):487–92.Google Scholar
  153. 153.
    Eisensehr I, Linke R, Noachtar S, Schwarz J, Gildehaus FJ, Tatsch K. Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson's disease and controls. Brain. 2000;123(Pt 6):1155–60.Google Scholar
  154. 154.
    Eisensehr I, Linke R, Tatsch K, Kharraz B, Gildehaus JF, Wetter CT, et al. Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson’s disease, and controls. Sleep. 2003;26(5):507–12.Google Scholar
  155. 155.
    Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected]. Lancet Neurol. 2010;9(11):1070–7.Google Scholar
  156. 156.
    Stiasny-Kolster K, Doerr Y, Moller JC, Hoffken H, Behr TM, Oertel WH, et al. Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain. 2005;128(Pt 1):126–37.Google Scholar
  157. 157.
    Unger MM, Moller JC, Stiasny-Kolster K, Mankel K, Berg D, Walter U, et al. Assessment of idiopathic rapid-eye-movement sleep behavior disorder by transcranial sonography, olfactory function test, and FP-CIT-SPECT. Mov Disord. 2008;23(4):596–9.Google Scholar
  158. 158.
    Rolinski M, Griffanti L, Piccini P, Roussakis AA, Szewczyk-Krolikowski K, Menke RA, et al. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease. Brain. 2016;139(Pt 8):2224–34.Google Scholar
  159. 159.
    Dang-Vu TT, Gagnon JF, Vendette M, Soucy JP, Postuma RB, Montplaisir J. Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder. Neurology. 2012;79(24):2302–6.Google Scholar
  160. 160.
    •• Yao C, Fereshtehnejad SM, Dawson BK, Pelletier A, Gan-Or Z, Gagnon JF, et al. Longstanding disease-free survival in idiopathic REM sleep behavior disorder: is neurodegeneration inevitable?, Parkinsonism Relat Disord, This study provides evidence that despite differences in phenoconversion rates, almost all individuals with iRBD appear to have underlying neurodegeneration. 2018;54:99–102.Google Scholar
  161. 161.
    Alhola P, Polo-Kantola P. Sleep deprivation: impact on cognitive performance. Neuropsychiatr Dis Treat. 2007;3(5):553–67.Google Scholar
  162. 162.
    Chee MW, Chuah LY. Functional neuroimaging insights into how sleep and sleep deprivation affect memory and cognition. Curr Opin Neurol. 2008;21(4):417–23.Google Scholar
  163. 163.
    Goel N, Rao H, Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol. 2009;29(4):320–39.Google Scholar
  164. 164.
    Wickwire EM, Williams SG, Roth T, Capaldi VF, Jaffe M, Moline M, et al. Sleep, sleep disorders, and mild traumatic brain injury. What we know and what we need to know: findings from a National Working Group. Neurotherapeutics. 2016;13(2):403–17.Google Scholar
  165. 165.
    Duss SB, Seiler A, Schmidt MH, Pace M, Adamantidis A, Müri RM, et al. The role of sleep in recovery following ischemic stroke: a review of human and animal data. Neurobiol Sleep Circadian Rhythms. 2017;2:94–105.Google Scholar
  166. 166.
    Kay DB, Dzierzewski JM. Sleep in the context of healthy aging and psychiatric syndromes. Sleep Med Clin. 2015;10(1):11–5.Google Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institut Universitaire de Gériatrie de Montréal and CRIUGMCIUSSS du Centre-Sud-de-l’Île-de-MontréalMontrealCanada
  2. 2.PERFORM Centre, Center for Studies in Behavioral Neurobiology, Department of Health, Kinesiology and Applied PhysiologyConcordia UniversityMontrealCanada
  3. 3.Center for Advanced Research in Sleep Medicine, Hopital du Sacre-Coeur de MontrealCIUSSS du Nord-de-l’Île-de-MontréalMontrealCanada
  4. 4.Department of PsychologyUniversité de MontréalMontrealCanada

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