Skip to main content

Cognitive Functioning

  • Chapter
  • First Online:
Restless Legs Syndrome/Willis Ekbom Disease
  • 680 Accesses

Abstract

This chapter reviews the available studies that investigated the effect of pharmacological treatment on cognitive functioning in WillisEkbom Disease/restless legs syndrome (WED/RLS). These studies included acute, single-night treatments with levodopa, clonazepam, ropinirole, and gabapetin and prolonged treatment with pramipexole, gabapentin enacarbil. Methodological concerns, the low number of available studies and heterogeneity of results impede any conclusions to be drawn at this time.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Allen RP, Bharmal M, Calloway M. Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord. 2011;26(1):114–20.

    Article  PubMed  Google Scholar 

  2. Fehnel S, Zografos L, Curtice T, Shah H, McLeod L. The burden of restless legs syndrome: an assessment of work productivity, sleep, psychological distress, and health status among diagnosed and undiagnosed individuals in an internet-based panel. Patient. 2008;1(3):201–10.

    Article  PubMed  Google Scholar 

  3. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165:1286–92.

    Article  PubMed  Google Scholar 

  4. Abetz L, Allen R, Follet A, Washburn T, Earley C, Kirsch J, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. 2004;26:925–35.

    Article  PubMed  Google Scholar 

  5. Abetz L, Vallow SM, Kirsch J, Allen RP, Washburn T, Earley CJ. Validation of the restless legs syndrome quality of life questionnaire. Value Health. 2005;8(2):157–67.

    Article  PubMed  Google Scholar 

  6. Kushida CA, Allen RP, Atkinson MJ. Modeling the causal relationships between symptoms associated with restless legs syndrome and the patient-reported impact of RLS. Sleep Med. 2004;5(5):485–8.

    Article  PubMed  Google Scholar 

  7. Happe S, Reese JP, Stiasny-Kolster K, Peglau I, Mayer G, Klotsche J, et al. Assessing health-related quality of life in patients with restless legs syndrome. Sleep Med. 2009;10:295–305.

    Article  PubMed  Google Scholar 

  8. Fulda S, Beitinger ME, Reppermund S, Winkelmann J, Wetter TC. Short-term attention and verbal fluency is decreased in restless legs syndrome patients. Mov Disord. 2010;25(15):2641–8.

    Article  PubMed  Google Scholar 

  9. Pearson VE, Allen RP, Dean T, Gamaldo CE, Lesage SR, Earley CJ. Cognitive deficits associated with restless legs syndrome (RLS). Sleep Med. 2006;7:25–30.

    Article  PubMed  Google Scholar 

  10. Jung K-Y, Koo Y-S, Kim B-J, Ko D, Lee G-T, Kim KH, et al. Electrophysiologic disturbances during daytime in patients with restless legs syndrome: further evidence of cognitive dysfunction? Sleep Med. 2011;12(4):416–21.

    Article  PubMed  Google Scholar 

  11. Choi JW, Ko D, Lee G-T, Jung K-Y, Kim KH. Reduced neural synchrony in patients with restless legs syndrome during a visual oddball task. PLoS ONE. 2012;7(7):e42312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fulda S, Szesny N, Ising M, Heck A, Grübl A, Lieb R, et al. Further evidence for executive dysfunction in subjects with RLS from a non-clinical sample. Sleep Med. 2011;13(12):1003–7.

    Article  Google Scholar 

  13. Galbiati A, Marelli S, Giora E, Zucconi M, Oldani A, Ferini-Strambi L. Neurocognitive function in patients with idiopathic restless legs syndrome before and after treatment with dopamine-agonist. Int J Psychophysiol. 2015;95(3):304–9.

    Google Scholar 

  14. Saletu B, Gruber G, Saletu M, Brandstätter N, Hauer C, Prause W, et al. Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 1. Findings on objective and subjective sleep and awakening quality. Neuropsychobiology. 2000;41(4):181–9.

    Article  CAS  PubMed  Google Scholar 

  15. Saletu M, Anderer P, Högl B, Saletu-Zyhlarz G, Kunz A, Poewe W, et al. Acute double-blind, placebo-controlled sleep laboratory and clinical follow-up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome. J Neural Transm. 2003;110(6):611–26.

    Article  CAS  PubMed  Google Scholar 

  16. Saletu M, Anderer P, Saletu-Zyhlarz G, Hauer C, Saletu B. Acute placebo-controlled sleep laboratory studies and clinical follow-up with pramipexole in restless legs syndrome. Eur Arch Psychiatry Clin Neurosci. 2002;252(4):185–94.

    Article  CAS  PubMed  Google Scholar 

  17. Saletu M, Anderer P, Saletu-Zyhlarz G, Prause W, Semler B, Zoghlami A, et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol. 2001;11(2):153–61.

    Article  CAS  PubMed  Google Scholar 

  18. Saletu M, Anderer P, Saletu-Zyhlarz GM, Parapatics S, Gruber G, Nia S, et al. Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome. J Neural Transm. 2010;117(4):463–73.

    Article  CAS  PubMed  Google Scholar 

  19. Grünberger J. Psychodiagnostik des Alkoholkranken. Ein methotischer Beitrag zur Bestimmung der Organizität in der Psychiatrie. Wien: Maudrich; 1977.

    Google Scholar 

  20. Kim M, Song J-Y, Kim SM, Moon YJ, Koo YS, Jung K-Y. Effect of pramipexole on cognitive functions in restless legs syndrome. J Korean Sleep Res Soc. 2014;11(1):16–20.

    Article  CAS  Google Scholar 

  21. GlaxoSmithKline. A randomized, double blind, active- and placebo-controlled, parallel group safety study assessing simulated driving performance in XP13512-(GSK1838262) treated patients with restless legs syndrome [Internet]. Available from: http://www.gsk-clinicalstudyregister.com/files2/df5702c2-01e4-4770-96fc-4da1ee565ab8.

  22. Winkelman JW, Bogan RK, Schmidt MH, Hudson JD, Derossett SE, Hill-Zabala CE. Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome. Mov Disord. 2011;26(11):2065–72.

    Article  PubMed  Google Scholar 

  23. Abler B, Hahlbrock R, Unrath A, Grön G, Kassubek J. At-risk for pathological gambling: imaging neural reward processing under chronic dopamine agonists. Brain. 2009;132(Pt 9):2396–402.

    Article  PubMed  Google Scholar 

  24. Lee HB, Ramsey CM, Spira AP, Vachon J, Allen R, Munro CA. Comparison of cognitive functioning among individuals with treated restless legs syndrome (RLS), untreated RLS, and No RLS. J Neuropsychiatry Clin Neurosci. 2014;26(1):87–91.

    Article  PubMed  Google Scholar 

  25. Fulda S, Schulz H. How treatment affects cognitive deficits in patients with sleep disorders: methodological issues and results. Prog Brain Res. 2010;185:69–90.

    Article  PubMed  Google Scholar 

  26. Fulda S, Schulz H. Cognitive dysfunction in sleep disorders. Sleep Med Rev. 2001;5(6):423–45.

    Article  CAS  PubMed  Google Scholar 

  27. Saletu B, Anderer P, Saletu M, Hauer C, Lindeck-Pozza L, Saletu-Zyhlarz G. EEG mapping, psychometric, and polysomnographic studies in restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) patients as compared with normal controls. Sleep Med. 2002;3(Suppl):S35–42.

    Article  PubMed  Google Scholar 

  28. Kim SM, Choi JW, Lee C, Lee BU, Koo YS, Kim KH, et al. Working memory deficit in patients with restless legs syndrome: an event-related potential study. Sleep Med. 2014;15(7):808–15.

    Article  PubMed  Google Scholar 

  29. Celle S, Roche F, Kerleroux J, Thomas-Anterion C, Laurent B, Rouch I, et al. Prevalence and clinical correlates of restless legs syndrome in an elderly French population: the synapse study. J Gerontol A Biol Sci Med Sci. 2010;65:167–73.

    Article  PubMed  Google Scholar 

  30. Chen D, Shaw P, Canafax DM, Ware J. A pilot study to evaluate simulated driving performance and cognitive function in healthy subjects and patients with restless legs syndrome. J Parkinsonism Restless Legs Syndr. 2013;53–62.

    Google Scholar 

  31. Driver-Dunckley E, Connor D, Hentz J, Sabbagh M, Silverberg N, Hernandez J, et al. No evidence for cognitive dysfunction or depression in patients with mild restless legs syndrome. Mov Disord. 2009;24:1843–7.

    Article  Google Scholar 

  32. Kim ES, Yoon IY, Kweon K, Park HY, Lee CS, Han EK, et al. Mild impairments in cognitive function in the elderly with restless legs syndrome. Sleep Med Psychophysiol. 2013;20(1):15–21.

    Article  Google Scholar 

  33. Calamia M, Markon K, Tranel D. Scoring higher the second time around: meta-analyses of practice effects in neuropsychological assessment. Clin Neuropsychol. 2012;26(4):543–70.

    Article  PubMed  Google Scholar 

  34. Hausknecht JP, Halpert JA, Di Paolo NT, Moriarty Gerrard MO. Retesting in selection: a meta-analysis of coaching and practice effects for tests of cognitive ability. J Appl Psychol. 2007;92(2):373–85.

    Article  PubMed  Google Scholar 

  35. Garcia-Borreguero D, Ferini-Strambi L, Kohnen R, O’Keeffe S, Trenkwalder C, Högl B, et al. European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. Eur J Neurol. 2012;19(11):1385–96.

    Article  PubMed  Google Scholar 

  36. Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Högl B, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013;14(7):675–84.

    Article  PubMed  Google Scholar 

  37. Hornyak M, Scholz H, Kohnen R, Bengel J, Kassubek J, Trenkwalder C. What treatment works best for restless legs syndrome? Meta-analyses of dopaminergic and non-dopaminergic medications. Sleep Med Rev. 2014;18(2):153–62.

    Google Scholar 

  38. Manconi M, Ferri R, Feroah TR, Zucconi M, Ferini-Strambi L. Defining the boundaries of the response of sleep leg movements to a single dose of dopamine agonist. Sleep. 2008;31(9):1229–37.

    PubMed  PubMed Central  Google Scholar 

  39. Manconi M, Ferri R, Zucconi M, Bassetti CL, Fulda S, Aricò D, et al. Dissociation of periodic leg movements from arousals in restless legs syndrome. Ann Neurol. 2012;71:834–44.

    Article  PubMed  Google Scholar 

  40. Ferri R, Manconi M, Aricò D, Sagrada C, Zucconi M, Bruni O, et al. Acute dopamine-agonist treatment in restless legs syndrome: effects on sleep architecture and NREM sleep instability. Sleep. 2010;33(6):793–800.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Montplaisir J, Boucher S, Gosselin A, Poirier G, Lavigne G. Persistence of repetitive EEG arousals (K-alpha complexes) in RLS patients treated with L-DOPA. Sleep. 1996;19(3):196–9.

    Article  CAS  PubMed  Google Scholar 

  42. Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002;59(10):1573–9.

    Article  CAS  PubMed  Google Scholar 

  43. Kushida CA, Walters AS, Becker P, Thein SG, Perkins AT, Roth T, et al. A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep. 2009;32(2):159–68.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Flöel A, Breitenstein C, Hummel F, Celnik P, Gingert C, Sawaki L, et al. Dopaminergic influences on formation of a motor memory. Ann Neurol. 2005;58(1):121–30.

    Article  PubMed  Google Scholar 

  45. Knecht S, Breitenstein C, Bushuven S, Wailke S, Kamping S, Flöel A, et al. Levodopa: faster and better word learning in normal humans. Ann Neurol. 2004;56(1):20–6.

    Article  CAS  PubMed  Google Scholar 

  46. Rihet P, Possamaï C-A, Micallef-Roll J, Blin O, Hasbroucq T. Dopamine and human information processing: a reaction-time analysis of the effect of levodopa in healthy subjects. Psychopharmacology. 2002;163(1):62–7.

    Article  CAS  PubMed  Google Scholar 

  47. Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep. 2005;28(7):891–8.

    PubMed  Google Scholar 

  48. Reppermund S, Zihl J, Lucae S, Horstmann S, Kloiber S, Holsboer F, et al. Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation. Biol Psychiatry. 2007;62(5):400–6.

    Article  CAS  PubMed  Google Scholar 

  49. Carvalho AF, Miskowiak KK, Hyphantis TN, Kohler CA, Alves GS, Bortolato B, et al. Cognitive dysfunction in depression—pathophysiology and novel targets. CNS Neurol Disord: Drug Targets. 2014;13(10):1819–35.

    Article  Google Scholar 

  50. Wang S, Blazer DG. Depression and cognition in the elderly. Annu Rev Clin Psychol. 2015.

    Google Scholar 

  51. Benes H, Mattern W, Peglau I, Dreykluft T, Bergmann L, Hansen C, et al. Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study. J Neurol. 2011;258(6):1046–54.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephany Fulda .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this chapter

Cite this chapter

Fulda, S. (2017). Cognitive Functioning. In: Manconi, M., García-Borreguero, D. (eds) Restless Legs Syndrome/Willis Ekbom Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6777-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6777-3_4

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-6775-9

  • Online ISBN: 978-1-4939-6777-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics