The effects of aerobic exercise on sleep quality measures and sleep-related biomarkers in individuals with Multiple Sclerosis: A pilot randomised controlled trial

Abstract

BACKGROUND:

Sleep disturbances are highly prevalent in people with multiple sclerosis(MS), and are associated with pain, fatigue, depression, and reduced quality of life (QoL). Importantly, sleep has been considered a critical brain state for motor learning and memory consolidation. Therefore, interventions that target sleep managementin people with MS are needed.

OBJECTIVES:

To explore the effects of a six weeks moderate-intensity aerobic exercise intervention on sleep characteristics and sleep-related biomarkers specifically serotonin, melatoninand cortisol in people with MS using a pilot randomized controlled trial.

METHODS:

Participants were randomly allocated to either a moderate-intensity aerobic exercise program (MAE, n = 20) or a home exercise program (HEP, n = 20). Participants were assessed at baseline and follow-up. Subjective and objective measures were used to assess sleep quality. The Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) were used to subjectively assess sleep. While Actigraphy was used to objectivelyassess sleep. Blood samples were collected for measurement of cortisol, melatonin and serotonin from MS participants in both groups at 8:00 am±1 hour.

RESULTS:

Seventeen participants in the MAE and 13 in the HEP group completed the study. Compared to the HEP group, people with MS who participated in a moderate-intensity aerobic exercise experienced significant improvements (P < 0.05) on the PSQI, ISI, and several objective sleep parameters measured using actigraphy. Only the serotonin levels increased significantly over the six-week period in the MAE group compared to the HEP group. The change score in serotonin (from baseline to follow up assessment) was significantly correlatedwith the change score in PSQI (r = –0.97, p < 001) and the change score in ISI (r = –0. 56, p = 0.015) only in the MAE group but not the HEP group.

CONCLUSIONS:

Exercise may be a non-pharmacological, inexpensive, safe method to improve sleep quality in people with MS. The improvement in the serotonin level due to aerobic exercisemight explain one of the physiologic mechanisms driving these improvements.

Keywords

Multiple sclerosis sleep motor training rehabilitation

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References

Aburub,

, Khalil,

, Al-Sharman,

, Alomari,

, Khabour,

(2017). The association between physical activity and sleep characteristics in people with multiple sclerosis. Multiple Sclerosis and Related Disorders 12, 29–33.

Bansi,

, Koliamitra,

, Bloch,

, Joisten,

, Schenk,

, Watson,

, … Kesselring,

(2018). Persons with secondary progressive and relapsing remitting multiple sclerosis reveal different responses of tryptophan metabolism to acute endurance exercise and training. Journal of Neuroimmunology 314, 101–105.

Bastien,

C. H.

, Vallières,

, Morin,

C. M.

(2001). Validation of the insomnia severity index as an outcome measure for insomnia research. Sleep Medicine 2(4), 297–307.

Brass,

S. D.

, Duquette,

, Proulx-Therrien,

, Auerbach,

(2010). Sleep disorders in patients with multiple sclerosis. Sleep medicine Reviews 14(2), 121–129.

Brawn,

T. P.

, Fenn,

K. M.

, Nusbaum,

H. C.

, Margoliash,

(2008). Consolidation of sensorimotor learning during sleep. Learning & Memory 15(11), 815–819.

Burks,

J. S.

, Bigley,

G. K.

, Hill,

H. H.

(2009). Rehabilitation challenges in multiple sclerosis. Ann Indian Acad Neurol 12(4), 296–306. doi: 10.4103/0972-2327.58273

Busse,

, Quinn,

, Khalil,

, Rosser,

(2009). Move to exercise”: Developing an exercise Dvd for people with huntington’s disease: F06. Clinical Genetics 76, 86.

Buysse,

D. J.

, Reynolds III,

C. F.

, Monk,

T. H.

, Berman,

S. R.

, Kupfer,

D. J.

(1989). The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Research 28(2), 193–213.

Camarda,

S. R. D. A.

, Tebexreni,

A. S.

, Páfaro,

C. N.

, Sasai,

F. B.

, Tambeiro,

V. L.

, Juliano,

, Barros Neto,

T. L. D.

(2008). Comparison of maximal heart rate using the prediction equations proposed by Karvonen and Tanaka. Arquivos Brasileiros de Cardiologia 91(5), 311–314.

10.

Clark,

C. M.

, Fleming,

J. A.

, Li,

, Oger,

, Klonoff,

, Paty,

(1992). Sleep disturbance, depression, and lesion site in patients with multiple sclerosis. Archives of Neurology 49(6), 641–643.

11.

Cohen,

Statistical power analysis for the behavioural sciences (Rev. ed.). Book.

12.

Cohen,

(1977). Statistical analysis for the behavioral sciences (Rev. ed.). New York: Academic Press.

13.

Cole,

R. J.

, Kripke,

D. F.

, Gruen,

, Mullaney,

D. J.

, Gillin,

J. C.

(1992). Automatic sleep/wake identification from wrist activity. Sleep 15(5), 461–469.

14.

Cowan,

, Stadler,

M. A.

(1996). Estimating unconscious processes: Implications of a general class of models. Journal of Experimental Psychology: General 125, 195–200.

15.

Dias,

R. A.

, Hardin,

K. A.

, Rose,

, Agius,

M. A.

, Apperson,

M. L.

, Brass,

S. D.

(2012). Sleepiness, fatigue, and risk of obstructive sleep apnea using the STOP-BANG questionnaire in multiple sclerosis: A pilot study. Sleep and Breathing 16(4), 1255–1265.

16.

Fleming,

W. E.

, Pollak,

C. P.

(2005). Sleep disorders in multiple sclerosis. Semin Neurol 25(1), 64–68. doi: 10.1055/s-2005-867075 [doi]

17.

Fleming,

W. E.

, Pollak,

C. P.

(2005). Sleep disorders in multiple sclerosis. Paper presented at the Seminars in neurology.

18.

Gomez-Choco,

M. J.

, Iranzo,

, Blanco,

, Graus,

, Santamaria,

, Saiz,

(2007). Prevalence of restless legs syndrome and REM sleep behavior disorder in multiple sclerosis. Mult Scler 13(6), 805–808. doi: 1352458506074644 [pii] 10.1177/1352458506074644 [doi]

19.

Hall,

J. E.

(2010), Guyton and Hall textbook of medical physiology e-Book: Elsevier Health Sciences.

20.

Hertzog,

M. A.

(2008). Considerations in determining sample size for pilot studies. Research in Nursing & Health 31(2), 180–191.

21.

Jelinek,

G. A.

, Weiland,

T. J.

, Hadgkiss,

E. J.

, Marck,

C. H.

, Pereira,

, van der Meer,

D. M.

(2015). Medication use in a large international sample of people with multiple sclerosis: Associations with quality of life, relapse rate and disability. Neurological Research 37(8), 662–673.

22.

Kallweit,

, Baumann,

C. R.

, Harzheim,

, Hidalgo,

, Pöhlau,

, Bassetti,

C. L.

, … Valko,

P. O.

(2013). Fatigue and sleep-disordered breathing in multiple sclerosis: A clinically relevant association? Multiple Sclerosis International 2013.

23.

Kaynak,

, Altintas,

, Kaynak,

, Uyanik,

, Saip,

, Agaoglu,

, … Siva,

(2006). Fatigue and sleep disturbance in multiple sclerosis. Eur J Neurol 13(12), 1333–1339.

24.

Khalil,

, Quinn,

, van Deursen,

, Martin,

, Rosser,

, Busse,

(2012). Adherence to use of a home-based exercise DVD in people with Huntington disease: Participants’ perspectives. Physical Therapy 92(1), 69–82.

25.

Lunde,

H. M. B.

, Aae,

T. F.

, Indrevag,

, Aarseth,

, Bjorvatn,

, Myhr,

K.-M.

, Bo,

(2012). Poor sleep in patients with multiple sclerosis. PloS One 7(11), e49996–e49996.

26.

Mann,

J. J.

, McBride,

P. A.

, Brown,

R. P.

, Linnoilam,

, Leon,

A. C.

, DeMeo,

, … Stanley,

(1992). Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients. Archives of General Psychiatry 49(6), 442–446.

27.

McDonald,

W. I.

, Compston,

, Edan,

, Goodkin,

, Hartung,

H. P.

, Lublin,

F. D.

, … Reingold,

S. C.

(2001). Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 50(1), 121–127.

28.

Medicine,

A. C. O. S.

(2013), ACSM’s guidelines for exercise testing and prescription: Lippincott Williams & Wilkins.

29.

Motl,

R. W.

, McAuley,

, Snook,

E. M.

(2005). Physical activity and multiple sclerosis: A meta-analysis. Multiple Sclerosis Journal 11(4), 459–463.

30.

Muratori,

L. M.

, Lamberg,

E. M.

, Quinn,

, Duff,

S. V.

(2013). Applying principles of motor learning and control to upper extremity rehabilitation. J Hand Ther 26(2), 94–102; quiz 103. doi: 10.1016/j.jht.2012.12.007

31.

Nagaraj,

, Taly,

A. B.

, Gupta,

, Prasad,

, Christopher,

(2013). Depression and sleep disturbances in patients with multiple sclerosis and correlation with associated fatigue. Journal of Neurosciences in Rural Practice 4(4), 387.

32.

Patrick,

R. P.

, Ames,

B. N.

(2015). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. The FASEB Journal 29(6), 2207–2222.

33.

Plazzi,

, Montagna,

(2002). Remitting REM sleep behavior disorder as the initial sign of multiple sclerosis. Sleep Med 3(5), 437–439. doi: S1389945702000424 [pii]

34.

Polman,

C. H.

, Reingold,

S. C.

, Banwell,

, Clanet,

, Cohen,

J. A.

, Filippi,

, … Kappos,

(2011). Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of Neurology 69(2), 292–302.

35.

Reid,

K. J.

, Baron,

K. G.

, Lu,

, Naylor,

, Wolfe,

, Zee,

P. C.

(2010). Aerobic exercise improves self-reported sleep and quality of life in older adults with insomnia. Sleep Medicine 11(9), 934–940.

36.

Scott,

N. W.

, McPherson,

G. C.

, Ramsay,

C. R.

, Campbell,

M. K.

(2002). The method of minimization for allocation to clinical trials: A review. Controlled Clinical Trials 23(6), 662–674.

37.

Siengsukon,

C. F.

, Aldughmi,

, Kahya,

, Bruce,

, Lynch,

, Ness Norouzinia,

, … Billinger,

(2016). Randomized controlled trial of exercise interventions to improve sleep quality and daytime sleepiness in individuals with multiple sclerosis: A pilot study. Multiple Sclerosis Journal–Experimental, Translational and Clinical 2, 2055217316680639.

38.

Singh,

N. A.

, Clements,

K. M.

, Fiatarone,

M. A.

(1997). A randomized controlled trial of the effect of exercise on sleep. Sleep 20(2), 95–101.

39.

Stanton,

B. R.

, Barnes,

, Silber,

(2006). Sleep and fatigue in multiple sclerosis. Mult Scler 12(4), 481–486.

40.

Tachibana,

, Howard,

, Hirsch,

, Miller,

, Moseley,

, Fish,

(1994). Sleep problems in multiple sclerosis. European Neurology 34(6), 320–323.

41.

Tachibana,

, Howard,

R. S.

, Hirsch,

N. P.

, Miller,

D. H.

, Moseley,

I. F.

, Fish,

(1994). Sleep problems in multiple sclerosis. Eur Neurol 34(6), 320–323.

42.

Tippmann-Peikert,

, Boeve,

B. F.

, Keegan,

B. M.

(2006). REM sleep behavior disorder initiated by acute brainstem multiple sclerosis. Neurology 66(8), 1277–1279. doi: 66/8/1277 [pii] 10.1212/01.wnl.0000208518.72660.ff [doi]

43.

Valim,

, Natour,

, Xiao,

, Pereira,

A. F. A.

, da Cunha Lopes,

B. B.

, Pollak,

D. F.

, … Russell,

I. J.

(2013). Effects of physical exercise on serum levels of serotonin and its metabolite in fibromyalgia: A randomized pilot study. Revista Brasileira De Reumatologia (English Edition) 53(6), 538–541.

44.

Varrasse,

, Li,

, Gooneratne,

(2015). Exercise and sleep in community-dwelling older adults. Current Sleep Medicine Reports 1(4), 232–240.