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Rapid eye movement sleep behavior disorder in patients with probable Alzheimer’s disease

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Abstract

Background and aims

Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with neurodegenerative disorders characterized by α-synuclein deposition, including Parkinson’s disease, multiple system atrophy, and Lewy body dementia. However, this tendency in tauopathy-mediated diseases is rare and only sporadically reported. We systematically illustrate the occurrence of RBD and sleep features among a cohort of patients with Alzheimer’s disease (AD), a non-synucleinopathy.

Methods

We recruited 105 clinically probable AD patients. Fifteen clinically probable AD patients with suspected RBD underwent a video-polysomnography (vPSG) examination.

Results

Five patients with probable AD exhibited RBD. One of the patients performed repeated touching of the head and the face with his hands and flailed his arms. Three patients exhibited hand twisting, exploring, prominent limb kicking, and jerking. The fifth patient exhibited all of the characteristics of RBD (he recalled a dream about fighting animals), and his wife was awakened by his screaming. Of these five patients, one patient took the acetylcholinesterase inhibitor drug donepezil. The patients with AD + RBD demonstrated increases in both tonic and phasic electromyography activity during REM sleep, but sleep architecture did not differ between the AD + RBD and AD-alone groups.

Conclusion

RBD can occur in patients with AD. The occurrence of RBD does not change the sleep architecture of AD patients.

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References

  1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement J Alzheimer’s Assoc 7(3):280–292. doi:10.1016/j.jalz.2011.03.003

    Article  Google Scholar 

  2. Tractenberg RE, Singer CM, Cummings JL, Thal LJ (2003) The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer’s disease. J Sleep Res 12(4):331–337

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bliwise DL (2004) Sleep disorders in Alzheimer’s disease and other dementias. Clinical cornerstone 6(Suppl 1A):S16–S28

    Article  PubMed  Google Scholar 

  4. Olson EJ, Boeve BF, Silber MH (2000) Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain J Neurol 123(Pt 2):331–339

    Article  Google Scholar 

  5. Stiasny-Kolster K, Doerr Y, Moller JC, Hoffken H, Behr TM, Oertel WH, Mayer G (2005) Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128(Pt 1):126–137. doi:10.1093/brain/awh322

    CAS  PubMed  Google Scholar 

  6. Wing YK, Li SX, Mok V, Lam SP, Tsoh J, Chan A, Yu MW, Lau CY, Zhang J, Ho CK (2012) Prospective outcome of rapid eye movement sleep behaviour disorder: psychiatric disorders as a potential early marker of Parkinson’s disease. J Neurol Neurosurg Psychiatry 83(4):470–472. doi:10.1136/jnnp-2011-301232

    Article  PubMed  Google Scholar 

  7. Iranzo A, Santamaria J, Rye DB, Valldeoriola F, Marti MJ, Munoz E, Vilaseca I, Tolosa E (2005) Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology 65(2):247–252. doi:10.1212/01.wnl.0000168864.97813.e0

    Article  CAS  PubMed  Google Scholar 

  8. Boeve BF, Silber MH, Ferman TJ, Kokmen E, Smith GE, Ivnik RJ, Parisi JE, Olson EJ, Petersen RC (1998) REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology 51(2):363–370

    Article  CAS  PubMed  Google Scholar 

  9. Kimura K, Tachibana N, Aso T, Kimura J, Shibasaki H (1997) Subclinical REM sleep behavior disorder in a patient with corticobasal degeneration. Sleep 20(10):891–894

    CAS  PubMed  Google Scholar 

  10. Gagnon JF, Petit D, Fantini ML, Rompre S, Gauthier S, Panisset M, Robillard A, Montplaisir J (2006) REM sleep behavior disorder and REM sleep without atonia in probable Alzheimer disease. Sleep 29(10):1321–1325

    PubMed  Google Scholar 

  11. Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J (2006) Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 5(5):424–432. doi:10.1016/S1474-4422(06)70441-0

    Article  PubMed  Google Scholar 

  12. Zhang Z, Liu Y, Jiang T, Zhou B, An N, Dai H, Wang P, Niu Y, Wang L, Zhang X (2012) Altered spontaneous activity in Alzheimer’s disease and mild cognitive impairment revealed by Regional Homogeneity. Neuroimage 59(2):1429–1440. doi:10.1016/j.neuroimage.2011.08.049

    Article  PubMed  Google Scholar 

  13. Wang P, Zhang X, Liu Y, Liu S, Zhou B, Zhang Z, Yao H, Jiang T (2013) Perceptual and response interference in Alzheimer’s disease and mild cognitive impairment. Clin Neurophysiol 124(12):2389–2396. doi:10.1016/j.clinph.2013.05.014

    Article  PubMed  Google Scholar 

  14. McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65(12):1863–1872. doi:10.1212/01.wnl.0000187889.17253.b1

    Article  CAS  PubMed  Google Scholar 

  15. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51(6):1546–1554

    Article  CAS  PubMed  Google Scholar 

  16. Boeve BF, Molano JR, Ferman TJ, Lin SC, Bieniek K, Tippmann-Peikert M, Boot B, St Louis EK, Knopman DS, Petersen RC, Silber MH (2013) Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med 9(5):475–480. doi:10.5664/jcsm.2670

    Google Scholar 

  17. Boeve BF, Molano JR, Ferman TJ, Smith GE, Lin SC, Bieniek K, Haidar W, Tippmann-Peikert M, Knopman DS, Graff-Radford NR, Lucas JA, Petersen RC, Silber MH (2011) Validation of the mayo sleep questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep Med 12(5):445–453. doi:10.1016/j.sleep.2010.12.009

    Article  PubMed  PubMed Central  Google Scholar 

  18. Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, Oertel W, Ju YE, Puligheddu M, Jennum P, Pelletier A, Wolfson C, Leu-Semenescu S, Frauscher B, Miyamoto M, Cochen De Cock V, Unger MM, Stiasny-Kolster K, Fantini ML, Montplaisir JY (2012) A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord Off J Mov Disord Society 27(7):913–916. doi:10.1002/mds.25037

    Article  Google Scholar 

  19. Boeve BF (2010) REM sleep behavior disorder: updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann NY Acad Sci 1184:15–54. doi:10.1111/j.1749-6632.2009.05115.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, Marcus CL, Mehra R, Parthasarathy S, Quan SF, Redline S, Strohl KP, Davidson Ward SL, Tangredi MM (2012) Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med 8(5):597–619. doi:10.5664/jcsm.2172

  21. Lapierre O, Montplaisir J (1992) Polysomnographic features of REM sleep behavior disorder: development of a scoring method. Neurology 42(7):1371–1374

    Article  CAS  PubMed  Google Scholar 

  22. Khachiyants N, Trinkle D, Son SJ, Kim KY (2011) Sundown syndrome in persons with dementia: an update. Psychiatry Investig 8(4):275–287. doi:10.4306/pi.2011.8.4.275

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lebert F, Pasquier F, Petit H (1996) Sundowning syndrome in demented patients without neuroleptic therapy. Arch Gerontol Geriatr 22(1):49–54

    Article  CAS  PubMed  Google Scholar 

  24. Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, Benarroch EE, Ahlskog JE, Smith GE, Caselli RC, Tippman-Peikert M, Olson EJ, Lin SC, Young T, Wszolek Z, Schenck CH, Mahowald MW, Castillo PR, Del Tredici K, Braak H (2007) Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130(Pt 11):2770–2788. doi:10.1093/brain/awm056

    Article  CAS  PubMed  Google Scholar 

  25. Morrison AR (1998) The pathophysiology of REM-sleep behavior disorder. Sleep 21(5):446–449

    CAS  PubMed  Google Scholar 

  26. Lai YY, Siegel JM (1988) Medullary regions mediating atonia. J Neurosci 8(12):4790–4796

    CAS  PubMed  Google Scholar 

  27. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211

    Article  PubMed  Google Scholar 

  28. Van Dijk KR, Sabuncu MR, Buckner RL (2012) The influence of head motion on intrinsic functional connectivity MRI. Neuroimage 59(1):431–438. doi:10.1016/j.neuroimage.2011.07.044

    Article  PubMed  Google Scholar 

  29. Achard S, Salvador R, Whitcher B, Suckling J, Bullmore E (2006) A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs. J Neurosci 26(1):63–72. doi:10.1523/JNEUROSCI.3874-05.2006

    Article  CAS  PubMed  Google Scholar 

  30. Salvador R, Suckling J, Coleman MR, Pickard JD, Menon D, Bullmore E (2005) Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb Cortex 15(9):1332–1342. doi:10.1093/cercor/bhi016

    Article  PubMed  Google Scholar 

  31. Liu Y, Yu C, Liang M, Li J, Tian L, Zhou Y, Qin W, Li K, Jiang T (2007) Whole brain functional connectivity in the early blind. Brain 130(Pt 8):2085–2096. doi:10.1093/brain/awm121

    Article  PubMed  Google Scholar 

  32. White KG, Ruske AC (2002) Memory deficits in Alzheimer’s disease: the encoding hypothesis and cholinergic function. Psychon Bull Rev 9(3):426–437

    Article  PubMed  Google Scholar 

  33. Boeve BF, Silber MH, Parisi JE, Dickson DW, Ferman TJ, Benarroch EE, Schmeichel AM, Smith GE, Petersen RC, Ahlskog JE, Matsumoto JY, Knopman DS, Schenck CH, Mahowald MW (2003) Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology 61(1):40–45

    Article  CAS  PubMed  Google Scholar 

  34. Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, Wszolek Z, Graff-Radford NR, Uitti R, Van Gerpen J, Pao W, Knopman D, Pankratz VS, Kantarci K, Boot B, Parisi JE, Dugger BN, Fujishiro H, Petersen RC, Dickson DW (2011) Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology 77(9):875–882. doi:10.1212/WNL.0b013e31822c9148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Eggers C, Szelies B, Bauer B, Wienhard K, Schroder H, Herholz K, Heiss WD (2007) Imaging of acetylcholine esterase activity in brainstem nuclei involved in regulation of sleep and wakefulness. Eur J Neurol 14(6):690–693. doi:10.1111/j.1468-1331.2007.01737.x

    Article  CAS  PubMed  Google Scholar 

  36. Mizuno S, Kameda A, Inagaki T, Horiguchi J (2004) Effects of donepezil on Alzheimer’s disease: the relationship between cognitive function and rapid eye movement sleep. Psychiatry Clin Neurosci 58(6):660–665. doi:10.1111/j.1440-1819.2004.01317.x

    Article  CAS  PubMed  Google Scholar 

  37. Nishino S, Tafti M, Reid MS, Shelton J, Siegel JM, Dement WC, Mignot E (1995) Muscle atonia is triggered by cholinergic stimulation of the basal forebrain: implication for the pathophysiology of canine narcolepsy. J Neurosci 15(7 Pt 1):4806–4814

    CAS  PubMed  Google Scholar 

  38. Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology 32(2):164–168

    Article  CAS  PubMed  Google Scholar 

  39. Heneka MT, Ramanathan M, Jacobs AH, Dumitrescu-Ozimek L, Bilkei-Gorzo A, Debeir T, Sastre M, Galldiks N, Zimmer A, Hoehn M, Heiss WD, Klockgether T, Staufenbiel M (2006) Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice. J Neurosci 26(5):1343–1354. doi:10.1523/JNEUROSCI.4236-05.2006

    Article  CAS  PubMed  Google Scholar 

  40. Iranzo A, Santamaria J (2005) Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep 28(2):203–206

    PubMed  Google Scholar 

  41. The incidence of dementia in Canada. The Canadian Study of Health and Aging Working Group (2000). Neurology 55(1):66–73

  42. Boeve BF, Silber MH, Ferman TJ, Lin SC, Benarroch EE, Schmeichel AM, Ahlskog JE, Caselli RJ, Jacobson S, Sabbagh M, Adler C, Woodruff B, Beach TG, Iranzo A, Gelpi E, Santamaria J, Tolosa E, Singer C, Mash DC, Luca C, Arnulf I, Duyckaerts C, Schenck CH, Mahowald MW, Dauvilliers Y, Graff-Radford NR, Wszolek ZK, Parisi JE, Dugger B, Murray ME, Dickson DW (2013) Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med 14(8):754–762. doi:10.1016/j.sleep.2012.10.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement J Alzheimer’s Assoc 7(3):263–269. doi:10.1016/j.jalz.2011.03.005

    Article  Google Scholar 

  44. Gagnon JF, Bedard MA, Fantini ML, Petit D, Panisset M, Rompre S, Carrier J, Montplaisir J (2002) REM sleep behavior disorder and REM sleep without atonia in Parkinson’s disease. Neurology 59(4):585–589

    Article  CAS  PubMed  Google Scholar 

  45. Schenck CH, Boeve BF, Mahowald MW (2013) 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 14(8):744–748. doi:10.1016/j.sleep.2012.10.009

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was partially supported by the National Natural Science Foundation of China (81471120, 60831004, and 61431012), the Natural Science Foundation of Beijing (Grant no. 7152096), the Specific Healthcare Research Projects (13BJZ50), the Clinical Sciences Fund of the Chinese PLA General Hospital (2013FC-TSYS-1006), and the Science Technological Innovation Nursery Fund of the Chinese PLA General Hospital (13KMM19).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation.

Informed consent

Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Department of Geriatric Neurology, Sleep Medicine Research Center, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, People’s Republic of China

    Pan Wang, Jianli Xing, Bo Zhou, Yan’e Guo, Yanchang Shang & Xi Zhang

  2. Department of Neurology, Tianjin Huanhu Hospital, Tianjin, 300060, China

    Pan Wang

  3. Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, SAR, Hong Kong, China

    Yun Kwok Wing

  4. Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China

    Yong Liu

  5. Department of Neurology, Hainan Branch of Chinese PLA General Hospital, Hainan, 572014, China

    Zengqiang Zhang

  6. Department of Radiology, Chinese PLA General Hospital, Beijing, 100853, China

    Hongxiang Yao

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  1. Pan Wang
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  2. Yun Kwok Wing
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  10. Xi Zhang
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Correspondence to Xi Zhang.

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Wang, P., Wing, Y.K., Xing, J. et al. Rapid eye movement sleep behavior disorder in patients with probable Alzheimer’s disease. Aging Clin Exp Res 28, 951–957 (2016). https://doi.org/10.1007/s40520-015-0382-8

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  • DOI: https://doi.org/10.1007/s40520-015-0382-8

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