Treatment of Sleep Disorders in Dementia

  • Sharon Ooms
  • Yo-El JuEmail author
Dementia (E McDade, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Dementia

Opinion statement

Sleep and circadian disorders occur frequently in all types of dementia. Due to the multifactorial nature of sleep problems in dementia, we propose a structured approach to the evaluation and treatment of these patients. Primary sleep disorders such as obstructive sleep apnea should be treated first. Comorbid conditions and medications that impact sleep should be optimally managed to minimize negative effects on sleep. Patients and caregivers should maintain good sleep hygiene, and social and physical activity should be encouraged during the daytime. Given the generally benign nature of bright light therapy and melatonin, these treatments should be tried first. Pharmacological treatments should be added cautiously, due to the risk of cognitive side effects, sedation, and falls in the demented and older population. Regardless of treatment modality, it is essential to follow patients with dementia and sleep disorders closely, with serial monitoring of individual response to treatment.


Sleep Insomnia Circadian Dementia Alzheimer’s disease Dementia with Lewy bodies Lewy body disease Vascular dementia Frontotemporal dementia Parkinson’s disease with dementia REM sleep behavior disorder 


Compliance with Ethical Standards

Conflict of Interest

Sharon Ooms declares no conflict of interest.

Yo-El Ju has received a grant from Philips Respironics and personal fees from C2N Diagnostics, the American Academy of Neurology, and the American Academy of Sleep Medicine.

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.

References and Recommended Reading

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

  1. 1.
    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):1255–73.PubMedGoogle Scholar
  2. 2.
    Tractenberg RE, Singer CM, Kaye JA. Symptoms of sleep disturbance in persons with Alzheimer’s disease and normal elderly. J Sleep Res. 2005;14(2):177–85.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Deschenes CL, McCurry SM. Current treatments for sleep disturbances in individuals with dementia. Curr Psychiatry Rep. 2009;11(1):20–6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Swaab DF, Fliers E, Partiman TS. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res. 1985;342(1):37–44.CrossRefPubMedGoogle Scholar
  5. 5.
    Monk TH. Sleep and circadian rhythms. Exp Gerontol. 1991;26(2–3):233–43.CrossRefPubMedGoogle Scholar
  6. 6.
    Bombois S, Derambure P, Pasquier F, Monaca C. Sleep disorders in aging and dementia. J Nutr Health Aging. 2010;14(3):212–7.CrossRefPubMedGoogle Scholar
  7. 7.
    McCurry SM, Logsdon RG, Teri L, Gibbons LE, Kukull WA, Bowen JD, et al. Characteristics of sleep disturbance in community-dwelling Alzheimer’s disease patients. J Geriatr Psychiatry Neurol. 1999;12(2):53–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Vitiello MV, Borson S. Sleep disturbances in patients with Alzheimer’s disease: epidemiology, pathophysiology and treatment. CNS Drugs. 2001;15(10):777–96.CrossRefPubMedGoogle Scholar
  9. 9.
    Ju YE, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013;70(5):587–93.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, et al. Self-reported sleep and beta-amyloid deposition in community-dwelling older adults. JAMA Neurol. 2013;70(12):1537–43.PubMedPubMedCentralGoogle Scholar
  11. 11.•
    Ju YE, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology—a bidirectional relationship. Nat Rev Neurol. 2014;10(2):115–9. This article reviews animal and human data supporting the bi-directional link between sleep disturbance and accumulation of amyloid-beta plaques, a pathological hallmark of Alzheimer's Disease.CrossRefPubMedGoogle Scholar
  12. 12.
    Dauvilliers Y. Insomnia in patients with neurodegenerative conditions. Sleep Med. 2007;8 Suppl 4:S27–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Reynolds 3rd CF, Kupfer DJ, Taska LS, Hoch CC, Sewitch DE, Restifo K, et al. Sleep apnea in Alzheimer’s dementia: correlation with mental deterioration. J Clin Psychiatry. 1985;46(7):257–61.PubMedGoogle Scholar
  14. 14.
    Ancoli-Israel S, Klauber MR, Butters N, Parker L, Kripke DF. Dementia in institutionalized elderly: relation to sleep apnea. J Am Geriatr Soc. 1991;39(3):258–63.CrossRefPubMedGoogle Scholar
  15. 15.
    Guarnieri B, Adorni F, Musicco M, Appollonio I, Bonanni E, Caffarra P, et al. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dement Geriatr Cogn Disord. 2012;33(1):50–8.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Boddy F, Rowan EN, Lett D, O'Brien JT, McKeith IG, Burn DJ. Subjectively reported sleep quality and excessive daytime somnolence in Parkinson’s disease with and without dementia, dementia with Lewy bodies and Alzheimer’s disease. Int J Geriatr Psychiatry. 2007;22(6):529–35.CrossRefPubMedGoogle Scholar
  17. 17.
    Ondo WG, Dat Vuong K, Khan H, Atassi F, Kwak C, Jankovic J. Daytime sleepiness and other sleep disorders in Parkinson’s disease. Neurology. 2001;57(8):1392–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Breen DP, Williams-Gray CH, Mason SL, Foltynie T, Barker RA. Excessive daytime sleepiness and its risk factors in incident Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2013;84(2):233–4.CrossRefPubMedGoogle Scholar
  19. 19.
    Fronczek R, Overeem S, Lee SY, Hegeman IM, van Pelt J, van Duinen SG, et al. Hypocretin (orexin) loss and sleep disturbances in Parkinson’s disease. Brain. 2008;131(Pt 1), e88.PubMedGoogle Scholar
  20. 20.
    Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol. 2015;72(6):707–12.CrossRefPubMedGoogle Scholar
  21. 21.
    Rijsman RM, Schoolderman LF, Rundervoort RS, Louter M. Restless legs syndrome in Parkinson’s disease. Parkinsonism Relat Disord. 2014;20 Suppl 1:S5–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Leung RS, Comondore VR, Ryan CM, Stevens D. Mechanisms of sleep-disordered breathing: causes and consequences. Pflugers Arch - Eur J Physiol. 2012;463(1):213–30.CrossRefGoogle Scholar
  23. 23.
    Harper DG, Stopa EG, McKee AC, Satlin A, Harlan PC, Goldstein R, et al. Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration. Arch Gen Psychiatry. 2001;58(4):353–60.CrossRefPubMedGoogle Scholar
  24. 24.
    Anderson KN, Hatfield C, Kipps C, Hastings M, Hodges JR. Disrupted sleep and circadian patterns in frontotemporal dementia. Eur J Neurol. 2009;16(3):317–23.CrossRefPubMedGoogle Scholar
  25. 25.
    Ancoli-Israel S, Ayalon L. Diagnosis and treatment of sleep disorders in older adults. Am J Geriatr Psychiatry. 2006;14(2):95–103.CrossRefPubMedGoogle Scholar
  26. 26.
    Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991;14(6):540–5.PubMedGoogle Scholar
  27. 27.
    Buysse DJ, Reynolds 3rd CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.CrossRefPubMedGoogle Scholar
  28. 28.
    Tractenberg RE, Singer CM, Cummings JL, Thal LJ. The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer’s disease. J Sleep Res. 2003;12(4):331–7.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hogl B, Arnulf I, Comella C, Ferreira J, Iranzo A, Tilley B, et al. Scales to assess sleep impairment in Parkinson’s disease: critique and recommendations. Mov Disord. 2010;25(16):2704–16.CrossRefPubMedGoogle Scholar
  30. 30.
    Morgenthaler T, Alessi C, Friedman L, Owens J, Kapur V, Boehlecke B, et al. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007. Sleep. 2007;30(4):519–29.PubMedGoogle Scholar
  31. 31.
    Masa JF, Corral J, Pereira R, Duran-Cantolla J, Cabello M, Hernandez-Blasco L, et al. Therapeutic decision-making for sleep apnea and hypopnea syndrome using home respiratory polygraphy: a large multicentric study. Am J Respir Crit Care Med. 2011;184(8):964–71.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.•
    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. This is the largest study demonstrating an association between obstructive sleep apnea and incident Alzheimer's Disease.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ancoli-Israel S, Palmer BW, Cooke JR, Corey-Bloom J, Fiorentino L, Natarajan L, et al. Cognitive effects of treating obstructive sleep apnea in Alzheimer’s disease: a randomized controlled study. J Am Geriatr Soc. 2008;56(11):2076–81.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cooke JR, Ayalon L, Palmer BW, Loredo JS, Corey-Bloom J, Natarajan L, 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(4):305–9.PubMedPubMedCentralGoogle Scholar
  36. 36.•
    Troussiere AC, Charley CM, Salleron J, Richard F, Delbeuck X, Derambure P, et al. Treatment of sleep apnoea syndrome decreases cognitive decline in patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2014;85(12):1405–8. This study provides a compelling reason to treat severe obstructive sleep apnea in Alzheimer's Disease patients.CrossRefPubMedGoogle Scholar
  37. 37.
    American Academy of Sleep Medicine. The International Classification of Sleep Disorders, Third Edition (ICSD-3). Darien: American Academy of Sleep Medicine; 2014.Google Scholar
  38. 38.
    Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR, Chowdhuri S, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010;6(1):85–95.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Fereshtehnejad SM, Romenets SR, Anang JB, Latreille V, Gagnon JF, Postuma RB. New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol. 2015;72(8):863–73.CrossRefPubMedGoogle Scholar
  40. 40.
    Hoch CC, Reynolds 3rd CF, Buysse DJ, Monk TH, Nowell P, Begley AE, et al. Protecting sleep quality in later life: a pilot study of bed restriction and sleep hygiene. J Gerontol B Psychol Sci Soc Sci. 2001;56(1):P52–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Alessi CA, Martin JL, Webber AP, Cynthia Kim E, Harker JO, Josephson KR. Randomized, controlled trial of a nonpharmacological intervention to improve abnormal sleep/wake patterns in nursing home residents. J Am Geriatr Soc. 2005;53(5):803–10.CrossRefPubMedGoogle Scholar
  42. 42.
    McCurry SM, Gibbons LE, Logsdon RG, Vitiello MV, Teri L. Nighttime insomnia treatment and education for Alzheimer’s disease: a randomized, controlled trial. J Am Geriatr Soc. 2005;53(5):793–802.CrossRefPubMedGoogle Scholar
  43. 43.
    McCurry SM, LaFazia DM, Pike KC, Logsdon RG, Teri L. Development and evaluation of a sleep education program for older adults with dementia living in adult family homes. Am J Geriatr Psychiatry. 2012;20(6):494–504.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Ouslander JG, Connell BR, Bliwise DL, Endeshaw Y, Griffiths P, Schnelle JF. A nonpharmacological intervention to improve sleep in nursing home patients: results of a controlled clinical trial. J Am Geriatr Soc. 2006;54(1):38–47.CrossRefPubMedGoogle Scholar
  45. 45.
    Naylor E, Penev PD, Orbeta L, Janssen I, Ortiz R, Colecchia EF, et al. Daily social and physical activity increases slow-wave sleep and daytime neuropsychological performance in the elderly. Sleep. 2000;23(1):87–95.PubMedGoogle Scholar
  46. 46.
    Benloucif S, Orbeta L, Ortiz R, Janssen I, Finkel SI, Bleiberg J, et al. Morning or evening activity improves neuropsychological performance and subjective sleep quality in older adults. Sleep. 2004;27(8):1542–51.PubMedGoogle Scholar
  47. 47.
    Richards KC, Lambert C, Beck CK, Bliwise DL, Evans WJ, Kalra GK, et al. Strength training, walking, and social activity improve sleep in nursing home and assisted living residents: randomized controlled trial. J Am Geriatr Soc. 2011;59(2):214–23.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Richards KC, Beck C, O'Sullivan PS, Shue VM. Effect of individualized social activity on sleep in nursing home residents with dementia. J Am Geriatr Soc. 2005;53(9):1510–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Eggermont LH, Blankevoort CG, Scherder EJ. Walking and night-time restlessness in mild-to-moderate dementia: a randomized controlled trial. Age Ageing. 2010;39(6):746–9.CrossRefPubMedGoogle Scholar
  50. 50.
    McCurry SM, Pike KC, Vitiello MV, Logsdon RG, Larson EB, Teri L. Increasing walking and bright light exposure to improve sleep in community-dwelling persons with Alzheimer’s disease: results of a randomized, controlled trial. J Am Geriatr Soc. 2011;59(8):1393–402.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Nascimento CM, Ayan C, Cancela JM, Gobbi LT, Gobbi S, Stella F. Effect of a multimodal exercise program on sleep disturbances and instrumental activities of daily living performance on Parkinson’s and Alzheimer’s disease patients. Geriatr Gerontol Int. 2014;14(2):259–66.CrossRefPubMedGoogle Scholar
  52. 52.
    Tewary S CN, Pandya N, McCurry SM. Pilot test of a six-week group delivery caregiver training program to reduce sleep disturbances among older adults with dementia-Innovative Practice. Dementia (London). 2016Google Scholar
  53. 53.
    Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, et al. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep. 2007;30(11):1445–59.PubMedPubMedCentralGoogle Scholar
  54. 54.•
    Forbes D, Blake CM, Thiessen EJ, Peacock S, Hawranik P. Light therapy for improving cognition, activities of daily living, sleep, challenging behaviour, and psychiatric disturbances in dementia. Cochrane Database Syst Rev. 2014;2, CD003946. This recent Cochrane meta-analysis reviews the effect of bright light therapy, not only on sleep but other symptoms of dementia.PubMedGoogle Scholar
  55. 55.
    Ancoli-Israel S, Gehrman P, Martin JL, Shochat T, Marler M, Corey-Bloom J, et al. Increased light exposure consolidates sleep and strengthens circadian rhythms in severe Alzheimer’s disease patients. Behav Sleep Med. 2003;1(1):22–36.CrossRefPubMedGoogle Scholar
  56. 56.
    Dowling GA, Mastick J, Hubbard EM, Luxenberg JS, Burr RL. Effect of timed bright light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease. Int J Geriatr Psychiatry. 2005;20(8):738–43.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Burns A, Allen H, Tomenson B, Duignan D, Byrne J. Bright light therapy for agitation in dementia: a randomized controlled trial. Int Psychogeriatr. 2009;21(4):711–21.CrossRefPubMedGoogle Scholar
  58. 58.
    Dowling GA, Burr RL, Van Someren EJ, Hubbard EM, Luxenberg JS, Mastick J, et al. Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease. J Am Geriatr Soc. 2008;56(2):239–46.CrossRefPubMedGoogle Scholar
  59. 59.
    Lyketsos CG, Lindell Veiel L, Baker A, Steele C. A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care. Int J Geriatr Psychiatry. 1999;14(7):520–5.CrossRefGoogle Scholar
  60. 60.
    Mishima K, Hishikawa Y, Okawa M. Randomized, dim light controlled, crossover test of morning bright light therapy for rest-activity rhythm disorders in patients with vascular dementia and dementia of Alzheimer’s type. Chronobiol Int. 1998;15(6):647–54.CrossRefPubMedGoogle Scholar
  61. 61.
    Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008;299(22):2642–55.CrossRefPubMedGoogle Scholar
  62. 62.
    Fontana Gasio P, Krauchi K, Cajochen C, Someren E, Amrhein I, Pache M, et al. Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly. Exp Gerontol. 2003;38(1–2):207–16.CrossRefPubMedGoogle Scholar
  63. 63.
    Nowak L. The effect of timed blue-green light on sleep-wake patterns in women with Alzheimer’s disease. Dissertation Abstracts International: Section B: The Sciences and Engineering. 2008:69(6-B):1–154.Google Scholar
  64. 64.
    Sloane PD, Figueiro M, Garg S, Cohen LW, Reed D, Williams CS, et al. Effect of home-based light treatment on persons with dementia and their caregivers. Light Res Technol. 2015;47(2):161–76.CrossRefPubMedGoogle Scholar
  65. 65.
    Figueiro MG, Plitnick BA, Lok A, Jones GE, Higgins P, Hornick TR, et al. Tailored lighting intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and related dementia living in long-term care facilities. Clin Interv Aging. 2014;9:1527–37.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.•
    van Maanen A, Meijer AM, van der Heijden KB, Oort FJ. The effects of light therapy on sleep problems: a systematic review and meta-analysis. Sleep Med Rev. 2015;29:52–62. This meta-analysis examines the effect of bright light therapy specifically on sleep.CrossRefPubMedGoogle Scholar
  67. 67.
    Fetveit A, Skjerve A, Bjorvatn B. Bright light treatment improves sleep in institutionalised elderly—an open trial. Int J Geriatr Psychiatry. 2003;18(6):520–6.CrossRefGoogle Scholar
  68. 68.
    Colenda CC, Cohen W, McCall WV, Rosenquist PB. Phototherapy for patients with Alzheimer disease with disturbed sleep patterns: results of a community-based pilot study. Alzheimer Dis Assoc Disord. 1997;11(3):175–8.CrossRefPubMedGoogle Scholar
  69. 69.
    Kobayashi R, Fukuda N, Kohsaka M, Sasamoto Y, Sakakibara S, Koyama E, et al. Effects of bright light at lunchtime on sleep of patients in a geriatric hospital I. Psychiatry Clin Neurosci. 2001;55(3):287–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Satlin A, Volicer L, Ross V, Herz L, Campbell S. Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer’s disease. Am J Psychiatry. 1992;149(8):1028–32.CrossRefPubMedGoogle Scholar
  71. 71.
    Skjerve A, Holsten F, Aarsland D, Bjorvatn B, Nygaard HA, Johansen IM. Improvement in behavioral symptoms and advance of activity acrophase after short-term bright light treatment in severe dementia. Psychiatry Clin Neurosci. 2004;58(4):343–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Kwok T, Leung PC, Wing YK, Ip I, Wong B, Ho DW, et al. The effectiveness of acupuncture on the sleep quality of elderly with dementia: a within-subjects trial. Clin Interv Aging. 2013;8:923–9.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Simoncini M, Gatti A, Quirico PE, Balla S, Capellero B, Obialero R, et al. Acupressure in insomnia and other sleep disorders in elderly institutionalized patients suffering from Alzheimer’s disease. Aging Clin Exp Res. 2015;27(1):37–42.CrossRefPubMedGoogle Scholar
  74. 74.
    Harris M, Richards KC, Grando VT. The effects of slow-stroke back massage on minutes of nighttime sleep in persons with dementia and sleep disturbances in the nursing home: a pilot study. J Holist Nurs. 2012;30(4):255–63.CrossRefPubMedGoogle Scholar
  75. 75.
    Wang W, Sawada M, Noriyama Y, Arita K, Ota T, Sadamatsu M, et al. Tai chi exercise versus rehabilitation for the elderly with cerebral vascular disorder: a single-blinded randomized controlled trial. Psychogeriatrics. 2010;10(3):160–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Tanaka M, Ishii A, Yamano E, Ogikubo H, Okazaki M, Kamimura K, et al. Effect of a human-type communication robot on cognitive function in elderly women living alone. Med Sci Monit. 2012;18(9):CR550–7.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Skene DJ, Vivien-Roels B, Sparks DL, Hunsaker JC, Pevet P, Ravid D, et al. Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer’s disease. Brain Res. 1990;528(1):170–4.CrossRefPubMedGoogle Scholar
  78. 78.
    Uchida K, Okamoto N, Ohara K, Morita Y. Daily rhythm of serum melatonin in patients with dementia of the degenerate type. Brain Res. 1996;717(1–2):154–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Cardinali DP, Vigo DE, Olivar N, Vidal MF, Furio AM, Brusco LI. Therapeutic application of melatonin in mild cognitive impairment. Am J Neurodegenerative Dis. 2012;1(3):280–91.Google Scholar
  80. 80.
    Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P. Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry. 2002;17(12):1120–7.CrossRefPubMedGoogle Scholar
  81. 81.
    Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, et al. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep. 2003;26(7):893–901.PubMedPubMedCentralGoogle Scholar
  82. 82.•
    McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer’s disease. Cochrane Database Syst Rev. 2014;3, CD009178. This comprehensive Cochrane meta-analysis reviews pharmacological therapies, including melatonin, for sleep disturbances.PubMedGoogle Scholar
  83. 83.
    Xu J, Wang LL, Dammer EB, Li CB, Xu G, Chen SD, et al. Melatonin for sleep disorders and cognition in dementia: a meta-analysis of randomized controlled trials. Am J Alzheimer's Dis Other Demen. 2015;30(5):439–47.CrossRefGoogle Scholar
  84. 84.
    Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S. Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch. 2003;70(4):334–41.CrossRefPubMedGoogle Scholar
  85. 85.
    Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S. Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry. 2009;17(2):166–9.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Gao QWLYG, Xiang W, Peng KR. Effect of melatonin on mild Alzheimer’s disease in elderly male patients. Parct Geriatr. 2009;23(1):56–8.Google Scholar
  87. 87.
    Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, et al. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014;9:947–61.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Clinical Trial Synopsis 01-05-TL-375-061, NCT# 00325728: a double-blind, randomized, placebo-controlled study of the efficacy, safety and tolerability of 8 week treatment of Rozerem 8 mg (QHS) in sleep disturbed, mild to moderately severe Alzheimer’s disease subjects. Accessed 18 June 2016.
  89. 89.
    Kasanuki K, Iseki E, Nishida Y, Fujishiro H, Chiba Y, Sato K, et al. Effectiveness of ramelteon for treatment of visual hallucinations in dementia with Lewy bodies: a report of 4 cases. J Clin Psychopharmacol. 2013;33(4):581–3.CrossRefPubMedGoogle Scholar
  90. 90.•
    Camargos EF, Louzada LL, Quintas JL, Naves JO, Louzada FM, Nobrega OT. Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study. Am J Geriatr Psychiatry. 2014;22(12):1565–74. To date, this study is the only randomized, controlled study of a non-melatonin medication showing a benefit on sleep in dementia.CrossRefPubMedGoogle Scholar
  91. 91.
    Scoralick FM, Louzada LL, Quintas JL, Naves JO, Camargos EF, Nobrega OT. Mirtazapine does not improve sleep disorders in Alzheimer’s disease: results from a double-blind, placebo-controlled pilot study. Psychogeriatrics. 2016.Google Scholar
  92. 92.
    Romeo R, Knapp M, Hellier J, Dewey M, Ballard C, Baldwin R, et al. Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial. Br J Psychiatry. 2013;202:121–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Vermeeren A, Coenen AM. Effects of the use of hypnotics on cognition. Prog Brain Res. 2011;190:89–103.CrossRefPubMedGoogle Scholar
  94. 94.
    Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, et al. Benzodiazepine use and risk of Alzheimer’s disease: case-control study. BMJ. 2014;349:g5205.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Defrancesco M, Marksteiner J, Fleischhacker WW, Blasko I. Use of benzodiazepines in Alzheimer’s disease: a systematic review of literature. Int J Neuropsychopharmacol. 2015;18(10):pyv055.Google Scholar
  96. 96.
    Rosenberg PB. Benzodiazepine exposure increases risk of Alzheimer’s disease. Evid Based Med. 2015;20(2):75.CrossRefPubMedGoogle Scholar
  97. 97.
    Zhang Y, Zhou XH, Meranus DH, Wang L, Kukull WA. Benzodiazepine use and cognitive decline in elderly with normal cognition. Alzheimer Dis Assoc Disord. 2016;30(2):113–7.CrossRefPubMedGoogle Scholar
  98. 98.
    Closser MH. Benzodiazepines and the elderly. A review of potential problems. J Subst Abus Treat. 1991;8(1–2):35–41.CrossRefGoogle Scholar
  99. 99.
    Larsson V, Aarsland D, Ballard C, Minthon L, Londos E. The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson’s disease dementia. Int J Geriatr Psychiatry. 2010;25(10):1030–8.CrossRefPubMedGoogle Scholar
  100. 100.
    Yin Y, Liu Y, Zhuang J, Pan X, Li P, Yang Y, et al. Low-dose atypical antipsychotic risperidone improves the 5-year outcome in Alzheimer’s disease patients with sleep disturbances. Pharmacology. 2015;96(3–4):155–62.CrossRefPubMedGoogle Scholar
  101. 101.
    Lou JS, Dimitrova DM, Park BS, Johnson SC, Eaton R, Arnold G, et al. Using modafinil to treat fatigue in Parkinson disease: a double-blind, placebo-controlled pilot study. Clin Neuropharmacol. 2009;32(6):305–10.CrossRefPubMedGoogle Scholar
  102. 102.
    Ondo WG, Fayle R, Atassi F, Jankovic J. Modafinil for daytime somnolence in Parkinson’s disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry. 2005;76(12):1636–9.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Geriatric MedicineRadboud University Medical CentreNijmegenThe Netherlands
  2. 2.Radboud Alzheimer CentreRadboud University Medical CentreNijmegenThe Netherlands
  3. 3.Department of NeurologyWashington University School of MedicineSaint LouisUSA

Personalised recommendations