Study Protocol for a Randomized Controlled Trial of Choral Singing Intervention to Prevent Cognitive Decline in At-Risk Older Adults Living in the Community

Jasmine Tan, F H Maurine Tsakok, Elisabeth K Ow, Bernard Lanskey, Kian Siong Darius Lim, Lee Gan Goh, Chay-Hoon Tan, Irwin Kee-Mun Cheah, Anis Larbi, Roger Foo, Marie Loh, Caroline Kai Yun Wong, John Suckling, Jialiang Li, Rathi Mahendran, Ee-Heok Kua, Lei Feng, Jasmine Tan, F H Maurine Tsakok, Elisabeth K Ow, Bernard Lanskey, Kian Siong Darius Lim, Lee Gan Goh, Chay-Hoon Tan, Irwin Kee-Mun Cheah, Anis Larbi, Roger Foo, Marie Loh, Caroline Kai Yun Wong, John Suckling, Jialiang Li, Rathi Mahendran, Ee-Heok Kua, Lei Feng

Abstract

Introduction: This study is a parallel-arm randomized controlled trial evaluating choral singing's efficacy and underlying mechanisms in preventing cognitive decline in at-risk older participants. Methods: Three-hundred and sixty community-dwelling, non-demented older participants are recruited for a 2-year intervention. Inclusion criteria are self-reported cognitive complaints, early cognitive impairment based on neuropsychological test scores or multiple risk factors of dementia. Participants are randomized to either weekly choral singing sessions or general health education. The primary outcome is cognitive performance, measured by a composite cognitive test score (CCTS). Secondary outcomes include depression, anxiety and neuropsychiatric symptoms; perceived stress; sleep quality and severity of dementia symptoms. Underlying mechanisms are examined using blood- and urine-based biomarkers and neuroimaging. Results: Screening began in July 2016. The first group of participants (n = 93) have been recruited. Intervention and control treatments are ongoing and will end in December 2019. Discussion: An evidence-based singing intervention for dementia prevention holds potential for healthcare savings and societal welfare. Trial Registration: NCT02919748, IRB Approval Number: NUS 2508.

Keywords: RCT; cognitive decline; dementia prevention; neuroplasticity; singing.

Figures

Figure 1
Figure 1
Theoretical model of choral singing’s efficacy in slowing cognitive decline and preventing dementia. Choral singing is hypothesized to delay cognitive decline and prevent dementia by increasing protection of the brain and reducing the risk burdens of dementia. As a complex activity, its effects can be attributed to the cognitive, social, emotional and physical aspects of choral singing. The biological mechanisms behind its effects may be observed from changes in brain structure and function and markers of biological aging.
Figure 2
Figure 2
Flow diagram of participants’ progression through phases of RCT as of May 2017. Adapted from Schulz et al. (2010). *Other reasons: four with hearing impairment, one with visual impairment, one with advanced cancer, two participating in other studies, two received recent neuropsychological assessment, one relocated outside the defined recruitment area.

References

    1. Bateman R. J., Benzinger T. L., Berry S., Clifford D. B., Duggan C., Fagan A. M., et al. . (2017). The DIAN-TU next generation Alzheimer’s prevention trial: adaptive design and disease progression model. Alzheimers Dement. 13, 8–19. 10.1016/j.jalz.2016.07.005
    1. Beck R. J., Cesario T. C., Yousefi A., Enamoto H. (2000). Choral singing, performance perception and immune system changes in salivary immunoglobulin A and cortisol. Music Percept. 18, 87–106. 10.2307/40285902
    1. Buysse D. J., Reynolds 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 Res. 28, 193–213. 10.1016/0165-1781(89)90047-4
    1. Clark I., Harding K. (2012). Psychosocial outcomes of active singing interventions for therapeutic purposes: a systematic review of the literature. Nord. J. Music Ther. 21, 80–98. 10.1080/08098131.2010.545136
    1. Clift S., Hancox G. (2010). The significance of choral singing for sustaining psychological wellbeing: findings from a survey of choristers in England, Australia and Germany. Music Perform. Res. 3, 79–96.
    1. Cohen S., Kamarck T., Mermelstein R. (1983). A global measure of perceived stress. J. Health Soc. Behav. 24, 385–396. 10.2307/2136404
    1. Cohen G. D., Perlstein S., Chapline J., Kelly J., Firth K. M., Simmens S. (2006). The impact of professionally conducted cultural programs on the physical health, mental health, and social functioning of older adults. Gerontologist 46, 726–734. 10.1093/geront/46.6.726
    1. Coley N., Gallini A., Ousset P. J., Vellas B., Andrieu S., GuidAge study group . (2016). Evaluating the clinical relevance of a cognitive composite outcome measure: an analysis of 1414 participants from the 5-year GuidAge Alzheimer’s prevention trial. Alzheimers Dement. 12, 1216–1225. 10.1016/j.jalz.2016.06.002
    1. Coulton S., Clift S., Skingley A., Rodriguez J. (2015). Effectiveness and cost-effectiveness of community singing on mental health-related quality of life of older people: randomised controlled trial. Br. J. Psychiatry 207, 250–255. 10.1192/bjp.bp.113.129908
    1. Cummings J. L., Mega M., Gray K., Rosenberg-Thompson S., Carusi D. A., Gornbein J. (1994). The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 44, 2308–2314. 10.1212/wnl.44.12.2308
    1. D’Elia L. F., Satz P., Uchiyama C. L., White T. (1996). Color Trails Test. Odessa: Psychological Assessment Resources (PAR).
    1. Engvig A., Fjell A. M., Westlye L. T., Moberget T., Sundseth Ø., Larsen V. A., et al. . (2010). Effects of memory training on cortical thickness in the elderly. Neuroimage 52, 1667–1676. 10.1016/j.neuroimage.2010.05.041
    1. Engvig A., Fjell A. M., Westlye L. T., Moberget T., Sundseth Ø., Larsen V. A., et al. . (2012). Memory training impacts short-term changes in aging white matter: a longitudinal diffusion tensor imaging study. Hum. Brain Mapp. 33, 2390–2406. 10.1002/hbm.21370
    1. Feng L., Chiu H., Chong M. Y., Yu X., Kua E. H. (2011). Dementia in Chinese populations: current data and future research. Asia Pac. Psychiatry 3, 109–114. 10.1111/j.1758-5872.2011.00137.x
    1. Feng L., Chong M. S., Lim W. S., Ng T. P. (2012). The modified mini-mental state examination test: normative data for Singapore Chinese older adults and its performance in detecting early cognitive impairment. Singapore Med. J. 53, 458–462.
    1. Feng L., Ng X.-T., Yap P., Li J., Lee T.-S., Håkansson K., et al. . (2014). Marital status and cognitive impairment among community-dwelling Chinese older adults: the role of gender and social engagement. Dement. Geriatr. Cogn. Dis. Extra 4, 375–384. 10.1159/000358584
    1. Folstein M. F., Folstein S. E., McHugh P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198. 10.1016/0022-3956(75)90026-6
    1. Hallam S., Creech A. (2016). Can active music making promote health and well-being in older citizens? Findings of the music for life project. London J. Prim. Care 8, 21–25. 10.1080/17571472.2016.1152099
    1. Herholz S. C., Zatorre R. J. (2012). Musical training as a framework for brain plasticity: behavior, function and structure. Neuron 76, 486–502. 10.1016/j.neuron.2012.10.011
    1. Horvath S. (2013). DNA methylation age of human tissues and cell types. Genome Biol. 14:3156. 10.1186/gb-2013-14-10-r115
    1. Hosseini S. M. H., Kramer J. H., Kesler S. R. (2014). Neural correlates of cognitive intervention in persons at risk of developing Alzheimer’s disease. Front. Aging Neurosci. 6:231. 10.3389/fnagi.2014.00231
    1. Houseman E. A., Molitor J., Marsit C. J. (2014). Genetics and population analysis Reference-free cell mixture adjustments in analysis of DNA methylation data. Bioinformatics 30, 1431–1439. 10.1093/bioinformatics/btu029
    1. Johnson J. K., Louhivuori J., Siljander E. (2017). Comparison of well-being of older adult choir singers and the general population in Finland: a case-control study. Music Sci. 21, 178–194. 10.1177/1029864916644486
    1. Kaplan E., Goodglass H., Weintraub S. (1983). Boston Naming Test. Philadelphia, PA: Lea and Febiger.
    1. Karp A., Paillard-Borg S., Wang H. X., Silverstein M., Winblad B., Fratiglioni L. (2006). Mental, physical and social components in leisure activities equally contribute to decrease dementia risk. Dement. Geriatr. Cogn. Disord. 21, 65–73. 10.1159/000089919
    1. Kreutz G., Univer C. V. O., Frank G., Kreutz G., Bongard S., Rohrmann S. (2005). Effects of choir singing or listening on secretory immunoglobulin A , cortisol, and emotional state. J. Behav. Med. 27, 623–635. 10.1007/s10865-004-0006-9
    1. Kua E. H., Mahendran R., Feng L., Tian X., Ng T.-P. (2013). Preventive psychiatry in late life: studies on depression and dementia from the Singapore gerontology research programme. Taiwan J. Psychiatry 27, 267–275.
    1. Lee T. S., Goh S. J. A., Quek S. Y., Phillips R., Guan C., Cheung Y. B., et al. . (2013). A brain-computer interface based cognitive training system for healthy elderly: a randomized control pilot study for usability and preliminary efficacy. PLoS One 8:e79419. 10.1371/journal.pone.0079419
    1. Lehne B., Drong A. W., Loh M., Zhang W., Scott W. R., Tan S.-T., et al. . (2015). A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies. Genome Biol. 16:37. 10.1186/s13059-015-0600-x
    1. Lustig C., Shah P., Seidler R., Reuter-Lorenz P. A. (2009). Aging, training and the brain: a review and future directions. Neuropsychol. Rev. 19, 504–522. 10.1007/s11065-009-9119-9
    1. Maguire L. E., Wanschura P. B., Battaglia M. M., Howell S. N., Flinn J. M. (2015). Participation in active singing leads to cognitive improvements in individuals with dementia. J. Am. Geriatr. Soc. 63, 815–816. 10.1111/jgs.13366
    1. Mormino E. C., Papp K. V., Rentz D. M., Donohue M. C., Amariglio R., Quiroz Y. T., et al. . (2017). Early and late change on the preclinical Alzheimer’s cognitive composite in clinically normal older individuals with elevated β-amyloid. Alzheimers Dement. 13, 1004–1012. 10.1016/j.jalz.2017.01.018
    1. Morris J. C. (1993). The clinical dementia rating (CDR): current version and scoring rules. Neurology 43, 2412–2414. 10.1212/wnl.43.11.2412-a
    1. Müllensiefen D., Gingras B., Musil J., Stewart L. (2014). The musicality of non-musicians: an index for assessing musical sophistication in the general population. PLoS One 9:e89642. 10.1371/journal.pone.0089642
    1. Nasreddine Z. S., Phillips N. A., Bédirian V., Charbonneau S., Whitehead V., Collin I., et al. . (2005). The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53, 695–699. 10.1111/j.1532-5415.2005.53221.x
    1. Pachana N. A., Byrne G. J., Siddle H., Koloski N., Harley E., Arnold E. (2007). Development and validation of the geriatric anxiety inventory. Int. Psychogeriatr. 19, 103–114. 10.1017/s1041610206003504
    1. Pidsley R., Zotenko E., Peters T. J., Lawrence M. G., Risbridger G. P., Molloy P., et al. . (2016). Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 17:208. 10.1101/194464
    1. Rey A. (1964). L’examen Clinique en Psychologie. 2nd Edn. Paris: Presses universitaires de France; Available online at: . Accessed May 1, 2017.
    1. Sandgren M. (2009). “Evidence for strong immediate well-being effects of choral singing - with more enjoyment for women than for men,” in Proceedings of the 7th Triennial Conference of European Society for the Cognitive Sciences of Music (ESCOM 2009), eds Louhivuori J., Eerola T., Saarikallio S., Himberg T., Eerola P. (Jyväskylä), 475–479.
    1. Särkämö T., Tervaniemi M., Laitinen S., Numminen A., Kurki M., Johnson J. K., et al. . (2014). Cognitive, emotional and social benefits of regular musical activities in early dementia: randomized controlled study. Gerontologist 54, 634–650. 10.1093/geront/gnt100
    1. Satoh M., Yuba T., Tabei K.-I., Okubo Y., Kida H., Sakuma H., et al. . (2015). Music therapy using singing training improves psychomotor speed in patients with Alzheimer’s disease: a neuropsychological and fMRI study. Dement. Geriatr. Cogn. Dis. Extra 5, 296–308. 10.1159/000436960
    1. Schulz K. F., Altman D. G., Moher D., CONSORT Group . (2010). CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 340:c332. 10.1136/bmj.c332
    1. Skingley A., Martin A., Clift S. (2015). The contribution of community singing groups to the well-being of older people: participant perspectives from the United Kingdom. J. Appl. Gerontol. 35, 1302–1324. 10.1177/0733464815577141
    1. Smith A. (2013). Symbol Digit Modalities Test: Manual. Available online at: . Accessed May 1, 2017.
    1. Staubo S. C., Aakre J. A., Vemuri P., Syrjanen J. A., Mielke M. M., Geda Y. E., et al. . (2017). Mediterranean diet, micronutrients and macronutrients and MRI measures of cortical thickness. Alzheimers Dement. 13, 168–177. 10.1016/j.jalz.2016.06.2359
    1. Valenzuela M., Sachdev P. (2009). Can cognitive exercise prevent the onset of dementia? Systematic review of randomized clinical trials with longitudinal follow-up. Am. J. Geriatr. Psychiatry 17, 179–187. 10.1097/JGP.0b013e3181953b57
    1. Wechsler D. (1997). Wechsler Memory Scale-Third Edition (WMS-III). San Antonio, TX: The Psychological Corporation.
    1. Willis S. L., Tennstedt S. L., Marsiske M., Ball K., Elias J., Koepke K. M., et al. . (2006). Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 296, 2805–2814. 10.1001/jama.296.23.2805
    1. Yesavage J. A., Sheikh J. I. (1986). 9/Geriatric depression scale (GDS). Clin. Gerontol. 5, 165–173. 10.1300/J018v05n01_09

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj