Abstract
Purpose of Review
The purpose of this paper was to address how sleep changes with aging, with the broader goal of informing how REM sleep and slow wave activity mechanisms interact to promote cognitive longevity.
Recent Findings
We conducted novel analyses based on the National Sleep Research Resource database. Over approximately 5 years, middle-to-older aged adults, on average, showed dramatically worse sleep fragmentation, a steady decrease in slow wave sleep, and yet a small increase in REM sleep. Averaging across participants, however, masked a major theme: Individuals differ substantially in their longitudinal trajectories for specific components of sleep. We considered this individual variability in light of recent theoretical and empirical work that has shown disrupted sleep and decreased slow wave activity to impair frontal lobe restoration, glymphatic system functioning, and memory consolidation. Based on multiple recent longitudinal studies, we contend that preserved or enhanced REM sleep may compensate for otherwise disrupted sleep in advancing age.
Summary
The scientific community has often debated whether slow wave activity or REM sleep mechanisms are more important to cognitive aging. We propose that a more fruitful approach for future work will be to investigate how REM and slow wave processes dynamically interact to affect cognitive longevity.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
• Jackson JH. The Croonian lectures on evolution and dissolution of the nervous system. BMJ 1884;1:703–7. He theorized about dissociable, interactive sleep-based cognitive processes one year before Ebbinghaus’ seminal work on the forgetting curve, and nearly 70 years before the discovery of sleep stages.
Bubu OM, Brannick M, Mortimer J, Umasabor-Bubu O, Sebastião YV, Wen Y, et al. Sleep, cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Sleep 2017;40:zsw032. https://doi.org/10.1093/sleep/zsw032.
Global Council on Brain Health. The brain-sleep connection: GCBH recommendations on sleep and brain health. American Association of Retired Persons. 2016. https://www.aarp.org/content/dam/aarp/health/healthy-living/2017/01/gcbh-recommendations-sleep-and-brain-health-aarp.pdf. Accessed 7 Sept 2018.
Miles LE, Dement WC. Sleep and aging. Sleep. 1980;3(2):1–220.
Mander BA, Winer JR, Walker MP. Sleep and human aging. Neuron. 2017;94(1):19–36. https://doi.org/10.1016/j.neuron.2017.02.004.
Scullin MK, Bliwise DL. Sleep, cognition, and normal aging: integrating a half-century of multidisciplinary research. Perspect Psychol Sci. 2015;10(1):97–137. https://doi.org/10.1177/1745691614556680.
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(7):1255–74. https://doi.org/10.1093/sleep/27.7.1255.
Zhang GQ, Cui L, Mueller R, Tao S, Kim M, Rueschman M, et al. The National Sleep Research Resource: towards a sleep data commons. J Am Med Inform Assoc. 2018;25:1351–8. https://doi.org/10.1093/jamia/ocy064.
• Dean DA 2nd, Goldberger AL, Mueller R, Kim M, Rueschman M, Mobley D, et al. Scaling up scientific discovery in sleep medicine: the National Sleep Research Resource. Sleep 2016;39(5):1151–64. https://doi.org/10.5665/sleep.5774. A publicly available resource for researchers to analyze polysomnography data from thousands of participants across the lifespan.
Quan SF, Howard BV, Iber C, Kiley JP, Nieto FJ, O’Connor GT, et al. The Sleep Heart Health Study: design, rationale, and methods. Sleep. 1997;20(12):1077–85.
Agnew HW, Webb WB, Williams RL. The first night effect: an EEG study of sleep. Psychophysiology. 1966;2(3):263–6.
Ohayon M, Wickwire EM, Hirshkowitz M, Albert SM, Avidan A, Daly FJ, et al. National Sleep Foundation’s sleep quality recommendations: first report. Sleep Health. 2017;3(1):6–19. https://doi.org/10.1016/j.sleh.2016.11.006.
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373–7. https://doi.org/10.1126/science.1241224.
Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The glymphatic system: a beginner’s guide. Neurochem Res. 2015;40(12):2583–99. https://doi.org/10.1007/s11064-015-1581-6.
Kress BT, Iliff JJ, Xia M, Wang M, Wei HS, Zeppenfeld D, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76(7):845–61. https://doi.org/10.1002/ana.24271.
Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E, et al. Suppression of glymphatic fluid transport in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2016;93:215–25. https://doi.org/10.1016/j.nbd.2016.05.015.
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(8):552–66. https://doi.org/10.1016/j.tins.2016.05.002.
Hwang JY, Byun MS, Choe YM, Lee JH, Yi D, Choi JW, et al. Moderating effect of APOE ε4 on the relationship between sleep-wake cycle and brain β-amyloid. Neurology. 2018;90(13):e1167–73. https://doi.org/10.1212/WNL.0000000000005193.
Musiek ES, Bhimasani M, Zangrilli MA, Morris JC, Holtzman DM, Ju YE. Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurol. 2018;75(5):582–90. https://doi.org/10.1001/jamaneurol.2017.4719.
Varga AW, Wohlleber ME, Giménez S, Romero S, Alonso JF, Ducca EL, et al. Reduced slow-wave sleep is associated with high cerebrospinal fluid Aβ42 levels in cognitively normal elderly. Sleep. 2016;39(11):2041–8.
Wilckens KA, Tudorascu DL, Snitz BE, Price JC, Aizenstein HJ, Lopez OL, et al. Sleep moderates the relationship between amyloid beta and memory recall. Neurobiol Aging. 2018;71:142–8. https://doi.org/10.1016/j.neurobiolaging.2018.07.011.
• Ju YE, Ooms SJ, Sutphen C, Macauley SL, Zangrilli MA, Jerome G, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain 2017;140(8):2104–11. https://doi.org/10.1093/brain/awx148. They cleverly manipulated sleep disruption via earphone-tones that responded to EEG spectral power. Though sleep disruption did not produce main effects on amyloid levels, there were dynamic changes in SWS and REM activity (in response to the disruption manipulation) that correlated with changes in amyloid levels.
Lucey BP, Hicks TJ, McLeland JS, Toedebusch CD, Boyd J, Elbert DL, et al. Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics. Ann Neurol. 2018;83(1):197–204. https://doi.org/10.1002/ana.25117.
Shokri-Kojori E, Wang GJ, Wiers CE, Demiral SB, Guo M, Kim SW, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci. 2018;115(17):4483–8. https://doi.org/10.1073/pnas.1721694115.
Kang JE, Cirrito JR, Dong H, Csernansky JG, Holtzman DM. Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity. Proc Natl Acad Sci. 2007;104(25):10673–8.
Krause AJ, Simon EB, Mander BA, Greer SM, Saletin JM, Goldstein-Piekarski AN, et al. The sleep-deprived human brain. Nat Rev Neurosci. 2017;18(7):404–18. https://doi.org/10.1038/nrn.2017.55.
Scullin MK. Do older adults need sleep? A review of neuroimaging, sleep, and aging studies. Curr Sleep Med Rep. 2017;3(3):204–14. https://doi.org/10.1007/s40675-017-0086-z.
Wilckens KA, Aizenstein HJ, Nofzinger EA, James JA, Hasler BP, Rosario-Rivera BL, et al. The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults. J Sleep Res. 2016;25:296–306. https://doi.org/10.1111/jsr.12365.
Van Der Werf YD, Altena E, Schoonheim MM, Sanz-Arigita EJ, Vis JC, De Rijke W, et al. Sleep benefits subsequent hippocampal functioning. Nat Neurosci. 2009;12:122–3.
della Monica C, Johnsen S, Atzori G, Groeger JA, Dijk DJ. Rapid eye movement sleep, sleep continuity and slow wave sleep as predictors of cognition, mood, and subjective sleep quality in healthy men and women, aged 20–84 years. Front Psychiatry. 2018;9:255. https://doi.org/10.3389/fpsyt.2018.00255.
Haba-Rubio J, Marti-Soler H, Tobback N, Andries D, Marques-Vidal P, Waeber G, et al. Sleep characteristics and cognitive impairment in the general population: the HypnoLaus study. Neurology. 2017;88:463–9. https://doi.org/10.1212/WNL.0000000000003557.
Song Y, Blackwell T, Yaffe K, Ancoli-Israel S, Redline S, Stone KL, et al. Relationships between sleep stages and changes in cognitive function in older men: the MrOS Sleep Study. Sleep. 2015;38:411–21. https://doi.org/10.5665/sleep.4500.
• Pase MP, Himali JJ, Grima NA, Beiser AS, Satizabal CL, Aparicio HJ, et al. Sleep architecture and the risk of incident dementia in the community. Neurology 2017;89:1244–50. https://doi.org/10.1212/WNL.0000000000004373. They conducted the longest longitudinal PSG and cognition study (that included a strong sample size). In so doing, they revealed that baseline REM and sleep fragmentation were predictive of faster cognitive decline.
Djonlagic I, Aeschbach D, Harrison SL, Dean D, Yaffe K, Ancoli-Israel S, et al. Associations between quantitative sleep EEG and subsequent cognitive decline in older women. J Sleep Res. 2018:e12666. https://doi.org/10.1111/jsr.12666.
Tranah GJ, Yaffe K, Nievergelt CM, Parimi N, Glymour MM, Ensrud KE, et al. APOEε4 and slow wave sleep in older adults. PLoS One. 2018;13(1):e0191281. https://doi.org/10.1371/journal.pone.0191281.
Brayet P, Petit D, Frauscher B, Gagnon JF, Gosselin N, Gagnon K, et al. Quantitative EEG of rapid-eye-movement sleep: a marker of amnestic mild cognitive impairment. Clin EEG Neurosci. 2016;47(2):134–41. https://doi.org/10.1177/1550059415603050.
• Kyle SD, Sexton CE, Feige B, Luik AI, Lane J, Saxena R, et al. Sleep and cognitive performance: cross-sectional associations in the UK Biobank. Sleep Med. 2017;38:85–91. https://doi.org/10.1016/j.sleep.2017.07.001 This study included nearly half a million participants, and their results highlighted the variability in positive, null, and negative results that are pervasive when looking across individual behavioral studies in the sleep, cognition and aging literature.
Gui WJ, Li HJ, Guo YH, Peng P, Lei X, Yu J. Age-related differences in sleep-based memory consolidation: a meta-analysis. Neuropsychologia. 2017;97:46–55. https://doi.org/10.1016/j.neuropsychologia.2017.02.001.
Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010;11(2):114–26. https://doi.org/10.1038/nrn2762.
Backhaus J, Born J, Hoeckesfeld R, Fokuhl S, Hohagen F, Junghanns K. Midlife decline in declarative memory consolidation is correlated with a decline in slow wave sleep. Learn Mem. 2007;14(5):336–41.
Jones BJ, Mackay A, Mantua J, Schultz KS, Spencer RM. The role of sleep in emotional memory processing in middle age. Neurobiol Learn Mem. 2018;155:208–15. https://doi.org/10.1016/j.nlm.2018.08.002.
Alger SE, Kensinger EA, Payne JD. Preferential consolidation of emotionally salient information during a nap is preserved in middle age. Neurobiol Aging. 2018;68:34–47. https://doi.org/10.1016/j.neurobiolaging.2018.03.030.
Spencer RM, Gouw AM, Ivry RB. Age-related decline of sleep-dependent consolidation. Learn Mem. 2007;14(7):480–4.
Wilson JK, Baran B, Pace-Schott EF, Ivry RB, Spencer RM. Sleep modulates word-pair learning but not motor sequence learning in healthy older adults. Neurobiol Aging. 2012;33(5):991–1000. https://doi.org/10.1016/j.neurobiolaging.2011.06.029.
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.
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(1):105–14. https://doi.org/10.1037/a0028830.
Scullin MK, Fairley J, Decker M, Bliwise DL. The effects of an afternoon nap on episodic memory in young and older adults. Sleep. 2017;40:zsx035. https://doi.org/10.1093/sleep/zsx035.
Cordi MJ, Schreiner T, Rasch B. No effect of vocabulary reactivation in older adults. Neuropsychologia. 2018;119:253–61. https://doi.org/10.1016/j.neuropsychologia.2018.08.021.
Debarnot U, Rossi M, Faraguna U, Schwartz S, Sebastiani L. Sleep does not facilitate insight in older adults. Neurobiol Learn Mem. 2017;140:106–13. https://doi.org/10.1016/j.nlm.2017.02.005.
Fogel SM, Albouy G, Vien C, Popovicci R, King BR, Hoge R, et al. fMRI and sleep correlates of the age-related impairment in motor memory consolidation. Hum Brain Mapp. 2014;35(8):3625–45. https://doi.org/10.1002/hbm.22426.
Fleischman DA, Wilson RS, Gabrieli JD, Bienias JL, Bennett DA. A longitudinal study of implicit and explicit memory in old persons. Psychol Aging. 2004;19(4):617–25.
Ackermann S, Hartmann F, Papassotiropoulos A, de Quervain DJ, Rasch B. No associations between interindividual differences in sleep parameters and episodic memory consolidation. Sleep. 2015;38(6):951–9. https://doi.org/10.5665/sleep.4748.
Latchoumane CV, Ngo HVV, Born J, Shin HS. Thalamic spindles promote memory formation during sleep through triple phase-locking of cortical, thalamic, and hippocampal rhythms. Neuron 2017;95(2):424–35.e6. https://doi.org/10.1016/j.neuron.2017.06.025.
Staresina BP, Bergmann TO, Bonnefond M, van der Meij R, Jensen O, Deuker L, et al. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep. Nat Neurosci. 2015;18(11):1679–86.
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(1):221–30. https://doi.org/10.1016/j.neuron.2017.11.020.
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. Neurobiol Aging. 2017;49:154–64. https://doi.org/10.1016/j.neurobiolaging.2016.10.009.
• Hornung OP, Regen F, Danker-Hopfe H, Schredl M, Heuser I. The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication. Biol Psychiatry 2007;61(6):750–7. Perhaps the largest intervention study for memory consolidation in older adults. They discovered that cholinesterase inhibitors improved memory consolidation, with the improvements potentially explained by augmenting both REM sleep and SWA (see ref 77).
Wilckens KA, Ferrarelli F, Walker MP, Buysse DJ. Slow-wave activity enhancement to improve cognition. Trends Neurosci. 2018;41(7):470–82. https://doi.org/10.1016/j.tins.2018.03.003.
Ladenbauer J, Külzow N, Passmann S, Antonenko D, Grittner U, Tamm S, et al. Brain stimulation during an afternoon nap boosts slow oscillatory activity and memory consolidation in older adults. Neuroimage. 2016;142:311–23. https://doi.org/10.1016/j.neuroimage.2016.06.057.
Ladenbauer J, Ladenbauer J, Külzow N, de Boor R, Avramova E, Grittner U, et al. Promoting sleep oscillations and their functional coupling by transcranial stimulation enhances memory consolidation in mild cognitive impairment. J Neurosci. 2017;37:7111–24. https://doi.org/10.1523/JNEUROSCI.0260-17.2017.
Westerberg CE, Florczak SM, Weintraub S, Mesulam MM, Marshall L, Zee PC, et al. Memory improvement via slow-oscillatory stimulation during sleep in older adults. Neurobiol Aging. 2015;36(9):2577–86. https://doi.org/10.1016/j.neurobiolaging.2015.05.014.
Papalambros NA, Santostasi G, Malkani RG, Braun R, Weintraub S, Paller KA, et al. Acoustic enhancement of sleep slow oscillations and concomitant memory improvement in older adults. Front Hum Neurosci. 2017;11:109. https://doi.org/10.3389/fnhum.2017.00109.
Eggert T, Dorn H, Sauter C, Nitsche MA, Bajbouj M, Danker-Hopfe H. No effects of slow oscillatory transcranial direct current stimulation (tDCS) on sleep-dependent memory consolidation in healthy elderly subjects. Brain Stimulation. 2013;6(6):938–45. https://doi.org/10.1016/j.brs.2013.05.006.
Paßmann S, Külzow N, Ladenbauer J, Antonenko D, Grittner U, Tamm S, et al. Boosting slow oscillatory activity using tDCS during early nocturnal slow wave sleep does not improve memory consolidation in healthy older adults. Brain Stimulation. 2016;9(5):730–9. https://doi.org/10.1016/j.brs.2016.04.016.
Manenti R, Sandrini M, Gobbi E, Cobelli C, Brambilla M, Binetti G, et al. Strengthening of existing episodic memories through non-invasive stimulation of prefrontal cortex in older adults with subjective memory complaints. Front Aging Neurosci. 2017;9:401. https://doi.org/10.3389/fnagi.2017.00401.
Lafon B, Henin S, Huang Y, Friedman D, Melloni L, Thesen T, et al. Low frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings. Nat Commun. 2017;8(1):1199. https://doi.org/10.1038/s41467-017-01045-x.
Bliwise DL. Sleep in normal aging and dementia. Sleep. 1993;16:40–81.
Lyamin OI, Kosenko PO, Korneva SM, Vyssotski AL, Mukhametov LM, Siegel JM. Fur seals suppress REM sleep for very long periods without subsequent rebound. Curr Biol. 2018;28(12):2000–5. https://doi.org/10.1016/j.cub.2018.05.022.
Symonds JA. Sleep and dreams, two lectures. London: Murray; 1851.
Ebbinghaus H. Ueber das Gedächtnis. Leipzig: Drucker & Humblat; 1885.
Aserinsky E, Kleitman N. Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science. 1953;118(3062):273–4.
Giuditta A, Ambrosini MV, Montagnese P, Mandile P, Cotugno M, Zucconi GG, et al. The sequential hypothesis of the function of sleep. Beh Brain Res. 1995;69:157–66.
Giuditta A. Sleep memory processing: the sequential hypothesis. Front Syst Neurosci. 2014;16:219. https://doi.org/10.3389/fnsys.2014.00219.
Llewellyn S, Hobson JA. Not only… but also: REM sleep creates and NREM stage 2 instantiates landmark junctions in cortical memory networks. Neurobiol Learn Mem. 2015;122:69–87. https://doi.org/10.1016/j.nlm.2015.04.005.
Gelber RP, Redline S, Ross GW, Petrovitch H, Sonnen JA, Zarow C, et al. Associations of brain lesions at autopsy with polysomnography features before death. Neurology. 2015;84:296–303. https://doi.org/10.1212/WNL.0000000000001163.
Hornung OP, Regen F, Dorn H, Anghelescu I, Kathmann N, Schredl M, et al. The effects of donepezil on postlearning sleep EEG of healthy older adults. Pharmacopsychiatry. 2009;42(01):9–13.
Kaiser J. The Alzheimer’s gamble: can the National Institute on Aging turn a funding windfall into a treatment for the dreaded brain disease? Science. 2018;361:839–41.
Horne J. Sleeplessness: assessing sleep need in society today. Leicestershire: Palgrave Macmillan; 2016.
Acknowledgments
The authors are appreciative to Yo-El Ju for helpful discussions on glymphatic functioning during the preparation of this manuscript.
Funding
This work was supported in part by NIH AG053161 (M.K.S.). The National Sleep Research Resource is supported by NIH HL114473.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Michael K. Scullin reports a grant for research on memory and aging by NIH AG053161.
Chenlu Gao declares 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.
Additional information
This article is part of the Topical Collection on Sleep and Aging
Rights and permissions
About this article
Cite this article
Scullin, M.K., Gao, C. Dynamic Contributions of Slow Wave Sleep and REM Sleep to Cognitive Longevity. Curr Sleep Medicine Rep 4, 284–293 (2018). https://doi.org/10.1007/s40675-018-0131-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40675-018-0131-6