This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting,pagination and proofreading process which may lead to differences between this version and the Version of Record.
Please cite this article as an ‘Accepted Article’, doi:10.2188/jea.JE20200051
Received March 2, 2020; accepted April 30, 2020; released online May 16, 2020

Original Article

Does laughter predict onset of functional disability and mortality among older
Japanese adults? the JAGES prospective cohort study

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Yudai Tamada 1 a, Kenji Takeuchi 1 a *, Chikae Yamaguchi 2, Masashige Saito 3, Tetsuya Ohira 4 5,
Kokoro Shirai 6, and Katsunori Kondo 7 8
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan;
2Ver

Department of Community Health Nursing, Nagoya City University School of Nursing, Aichi,
Japan; 3Department of Social Welfare, Nihon Fukushi University, Aichi, Japan; 4Department of
Epidemiology, Fukushima Medical University School of Medicine, Fukushima, Japan; 5Radiation
Medical Science Center for Fukushima Health Management Survey, Fukushima Medical University,
Fukushima, Japan; 6Department of Social Medicine, Public Health, Graduate School of Medicine,

These authors equally contributed to the work.

*Correspondence:

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Osaka University, Osaka, Japan; 7Department of Social Preventive Medical Sciences, Center for
Preventive Medical Sciences, Chiba University, Chiba, Japan; 8Department of Gerontological
Evaluation, Center for Gerontology and Social Science, National Center for Geriatrics andGerontology, Aichi, Japan.

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ceKenji Takeuchi
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65
Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
E-mail: k.takeuchi@med.nagoya-u.ac.jp
Short Title: Laughter, functional disability, mortality
Itemized list:
Word count for abstract: 250 words
Word count for text: 2,394 words (without abstract and acknowledgements)
Number of references: 34
Number of tables: 2
Number of figures: 1

1
Copyright © 2020 Yudai Tamada et al. This is an open access article distributed under the terms of Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract
Background: While laughter is broadly recognized as a good medicine, a potential
preventive effect of laughter on disability and death is still being debated. Accordingly,nwe investigated the association between the frequency of laughter and onset ofsiofunctional disability and all-cause mortality among the older adults in Japan.

Methods: The data for a 3-year follow-up cohort including 14,233 individuals (50.3%Vermen) aged ≥ 65 years who could independently perform the activities of daily living andparticipated in the Japan Gerontological Evaluation Study were analyzed. The
participants were classified into four categories according to their frequency of laughter(almost every day, 1–5 days/week, 1–3 days/month, and never or almost never). We

edestimated the risks of functional disability and all-cause mortality in each category
using a Cox proportional hazards model.

ptResults: During follow-up, 605 (4.3%) individuals developed functional disability,ce

identified by new certification for the requirement of Long-Term Care Insurance, and659 (4.6%) deaths were noted. After adjusting for the potential confounders, theAcmultivariate-adjusted hazard ratio of functional disability increased with a decrease in
the frequency of laughter (p for trend = 0.04). The risk of functional disability was 1.42
times higher for individuals who laughed never or almost never than for those wholaughed almost every day. No such association was observed with the risk of all-cause
mortality (p for trend = 0.39).
Conclusions: Low frequency of laughter is associated with increased risks of functional
disability. Laughter may be an early predictor of functional disability later on in life.

Key words: laughter, long-term care, death, cohort study, Japan2

Introduction
Increasing functional disability, defined as difficulty in performing theactivities of daily living, is a significantly important public health concern in rapidlynaging societies worldwide.1 Particularly in Japan, one-fourth of its population of 127

siomillion people is now aged ≥ 65 years.2 Furthermore, the number of people certified
with functional disability has increased by nearly 1.4 times in the past decade,accounting for 17.3% of the Japanese population aged ≥ 65 years.3 Identifying theVerfactors for preventing incident functional disability is a critical goal for super-agedsocieties, including Japan, because age-related functional disability negatively affects an
individual’s health status, predicts mortality,4 and increases the healthcare costsedassociated with long-term care and hospital services.5,6

Laughter could potentially be regarded as medicine. Recently, an increasingpt

number of studies have reported the beneficial effects of laughter on several healthoutcomes among older adults, such as on the cardiovascular functions and diseases andcemental health.7–11 However, studies assessing the association between laughter andfunctional disability and mortality, while considering the individuals’ socioeconomicAcbackground, have not been reported. The frequency of laughter can vary according to anindividual’s socioeconomic status,12 which is associated with the late-life healthtrajectories.13 The socioeconomic status can be considered a common cause of theassociation between laughter and health outcomes. Therefore, by targeting a large
general population of community-dwelling older adults, this prospective cohort study
aimed to test the hypothesis that low frequency of laughter is associated with a higher
risk of onset of functional disability and all-cause mortality when the socioeconomic
status is taken into consideration.

3

Methods
Study sample
This study was based on the cohort data from the Japan Gerontologicaln

Evaluation Study (JAGES),14 which is an ongoing longitudinal study investigating thesiofactors associated with health and well-being in the community-dwelling adults aged ≥65 years who could independently perform the physical and cognitive activities of dailyliving. Functional independency was defined as not being certified for Japan’s nationalVerLong-term Care Insurance system. We used the data of the 2013 wave (from October toDecember). In the 2013 wave, self-reported questionnaires were mailed to 193,694
community-dwelling elderly adults aged ≥ 65 years in 30 municipalities; of these,ed

137,736 individuals responded to the survey (response rate = 71.1%). The questionnaire
comprised basic questions and five modules that covered different topics, as follows:pt

module A, nursing care and medical care and lifestyles; module B, oral hygiene,
optimism, and subjective health; module C, social capital and history of abuse; moduleceD, subjective quality of life, sleep, and cognitive function; and module E, physicalactivity. Of the respondents, 21,377 individuals in 23 municipalities in 9 (out of 47)

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prefectures responded to the basic questions and module B, including questions about
laughter, in the questionnaire of the JAGES. Of the eligible sample of 21,377
individuals, 20,714 were successfully associated with the administrative records in 2016,
corresponding to a follow-up rate of 96.9%. After excluding 6,481 participants withmissing information regarding the frequency of laughter (n=958), annual householdincome (n=3,191), medical history (n=878), and survey questions on other covariates
used in the analysis (n=1454), we finally analyzed the data of 14,233 participants (men,7,162; women, 7,071).

4Outcomes
The outcomes of the present study were the onset of functional disability andnall-cause mortality obtained from the municipal and national databases. The onset ofsiofunctional disability was determined when an individual was newly certified forLong-term Care Insurance level 2–5,15,16 which is based on a multistep assessment offunctional and cognitive impairments by a qualified investigator and on comments fromVer

the family physician.17 Information regarding the onset of mortality was obtained fromthe administrative databases of the national Long-term Care Insurance registers. Theseeddefinitions were used in previous epidemiological studies.18,19

Exposurept

The daily frequency of laughter was measured based on the response to thefollowing standard single-item question: “How often do you laugh out loud?” Thecepossible item answers were as follows: almost every day, 1–5 days per week, 1–3 days
per month, or never or almost never. The 1-year test-retest reliability of the questionAc

was reported in a previous study20; subsequently, regional and seasonal differences inthe daily frequency of laughter among the Japanese men and women were not observed.
This item had been used in several previous studies.8,9,12,21

Covariates
We included a wide range of covariates in the analyses as potential
confounders based on prior literature.8,9,12,18,21 Information on sex, age, hypertension,
diabetes mellitus, smoking habit, alcohol intake, family structure , social participation,5

depressive symptoms, cognitive function, instrumental activities of daily living (IADL),
educational attainment, and equivalent income was obtained from a self-administeredquestionnaire. Smoking habit and alcohol intake were classified into the following threencategories: current, ever, and never. We considered the respondents who answered “Yes”

sioto the question, “Have you ever been diagnosed with hypertension or diabetes mellitus?”
as participants with hypertension or diabetes mellitus, respectively. Family structure
was assessed through two questions, one related to marital status and the other toVernumber of people living together. The marital status question provided five answer
categories (married, bereaved, divorced, never married and other). According to the
responses to these questions, family structure was classified into four groups: alone, ≥2edwithout partner, ≥2 with partner, or ≥2 with no information about marital status. Social
participation was defined as the person’s involvement in social activities (e.g., volunteer

ptgroup, sports group or club, leisure activity group, senior citizen club, neighborhood
association or residents’ association, study or cultural group, nursing care prevention orcehealth building, teaching skills or passing on experiences to others, local events). We
defined the participants who engaged in one or more of the social activities more thanAc

once per week as socially active. To assess the depressive symptoms, we used the15-item Geriatric Depression Scale; the participants were categorized into the following
two groups based on the scores: not depressed (0–4 points) and depressed (≥ 5
points).22,23 Cognitive function was assessed through three questions (part of the Kihon
Check-list,24 a basic function checklist in Japanese): First, Do your family or yourfriends point out your memory loss? Second, Do you make a call by looking up phone
numbers? Third, Do you find yourself not knowing today’s date? Participants are asked
to respond either “negative” (score: 1) or “positive” (score: 0). We divided the6participants into the following two groups based on the scores: Decline (1–3 points) andNormal (0 point). Our assessment of IADL was based on a five-item subscale of theTokyo Metropolitan Institute of Gerontology Higher Competence Scale.25 Wencategorized those who had difficulty with at least one item as ‘dependent’; others weresiocategorized as ‘independent.’ Attainment of education and annual equivalent income
served as indicators of the socioeconomic status. Attainment of education was evaluatedbased on the self-reported history of education and was classified into two categories (≤Ver

9 years and ≥ 10 years). The equivalent income was divided into nine categories (≤14,900$, 15,000–19,900$, 20,000–24,900$, 25,000–29,900$, 30,000–34,900$, 35,000–

Statistical analysis

ed39,900$, 40,000–45,900$ 45,000–49,900$, and ≥ 50,000$).

pt

For the demographic characteristics, summary statistics were constructed using
frequencies for categorical variables. Linear trends regarding the frequencies of riskcefactors according to the frequency of laughter categories were tested using logistic
regression analysis. Cox proportional hazards model was used to estimate the crude andAc

adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for the onset offunctional disability and all-cause mortality according to the frequency of laughter. In
multivariate adjustment, all covariates (sex, age, hypertension, diabetes mellitus,
smoking habit, alcohol intake, marital status, social participation, depressive symptoms,
educational attainment, and equivalent income) were included. All statistical analyses
were performed using the International Business Machines Corporation Statistical
Package for the Social Sciences (SPSS) version 25 statistical software (SPSS, Inc.), andtwo-sided p-values < 0.05 were considered statistically significant in all cases.

7

Ethical issues
Our study protocol and informed consent procedure were approved by thenEthics Committee on Research of Human Subjects at Nihon Fukushi University (August

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6, 2013, No 13-14).

8

Results
Table 1 shows the baseline characteristics of the study population according to
the frequency of laughter. The likelihood of being female, being socially active, andnhaving 10 years or more of education increased gradually with the increasing frequencysioof laughter. The likelihood of having been diagnosed with diabetes mellitus, being withcognitive decline, being dependent in IADL and being depressed decreased graduallywith the increasing frequency of laughter. The frequency of age, smoking habit, alcoholVerintake, family structure, and equivalent income categories were significantly different
across the frequency of laughter categories.

During follow-up (median, 3.3 years), 605 (4.3%) individuals developed

edfunctional disability and 659 (4.6%) deaths were noted. The all-cause mortality andfunctional disability rates were compared according to the daily frequency of laughterptusing the Kaplan-Meier method. Functional disability and all-cause mortality were morecommonly observed among participants with a low frequency of laughter (log-rank test,cep < 0.001, Figure 1A and log-rank test, p < 0.001, Figure 1B, respectively).
Table 2 shows the results of Cox proportional hazards analysis for theAcassociation of the frequency of laughter and functional disability and all-cause mortality.
In the crude model, significantly inverse associations between the frequency of laughterand functional disability (p for trend < 0.001) and all-cause mortality (p for trend <0.001) were observed. These inverse associations remained significant after adjustingfor sex and age (functional disability, p for trend < 0.001; all-cause mortality, p for
trend

=

0.001).

After

adjusting

for

the

abovementioned

covariates,themultivariate-adjusted HR of functional disability increased with a decrease in thefrequency of laughter (p for trend = 0.04). The risk of developing functional disability

9was 1.42 times higher for individuals who laughed never or almost never than for those
who laughed almost every day (95% CI, 1.10-1.85). However, no such association was

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observed with the risk of all-cause mortality (p for trend = 0.39).

10

Discussion
To the best of our knowledge, this is the first study to comprehensively
examine the association between laughter and functional disability and all-causenmortality after carefully controlling for the potential confounders, such as thesiosocioeconomic status. The present prospective cohort study of community-dwellingJapanese older adults revealed an inverse association between the daily frequency oflaughter and onset of functional disability, indicating that participants with a lowerVerfrequency of laughter were at higher risk of the onset of functional disability.
Particularly, laughing never or almost never could increase the risk of functional
disability by nearly 50%. In this study, approximately one-fifth of the participantsedlaughed less than once per week; hence, it is reasonable to hypothesize that publichealth efforts regarding the dissemination of information on the importance of laughterpt

to reduce the future incidence of functional disability predicting mortality among theolder adults are warranted.

ce

While published reports indicating the association between the frequency oflaughter and functional disability are not currently available, several previous reports

Ac

revealed that the daily frequency of laughter was associated with the prevalence andincidence of cardiovascular diseases,8,21 which constitute the second leading cause offunctional disability in Japan.26 Based on our present results being in line with theseprevious findings, we provide valuable new evidence that the low frequency of laughter
itself contributes to the development of functional disability, independent of theestablished confounders.
There are several plausible mechanisms underlying the association between
laughter and functional disability among the older adults. First, laughter might produce

11physiological changes in various systems of the body,27 such as improvement of theimmune function28 and stimulation of circulation.29 In turn, a low frequency of laughter
can trigger functional impairments. Second, a high frequency of laughter may be anmarker of positive emotions in daily life, which is associated with lower functionalsiolimitations.30 Moreover, laughter-related positive emotions are able to downregulate thecardiovascular aftereffects of negative emotions, which can serve as a buffer against
functional disability.31 Finally, laughter can play a role in buffering the effects of stress.

Ver

For example, stimulated and spontaneous laughter is reported to decrease salivary
cortisol level, a biomarker of stress.32,33 Thus, individuals with a higher frequency oflaughter may cope more effectively with stress than individuals with a lower frequency

edof laughter, which may moderate the adverse effects of stress on the individuals’
physical health.

ptRegarding all-cause mortality, our study revealed that age- and sex-adjusted
HR of all-cause mortality increased with a decrease in the daily frequency of laughter,cebut this inverse association was insignificant after adjusting for all covariates.
Meanwhile, a recent previous study21 reported a significant association between theAcdaily frequency of laughter and all-cause mortality. This discrepancy is possibly
attributed to the differences in the study settings (nine prefectures covering a wide area
in Japan vs one prefecture), participants (a general population of community-dwellingolder adults vs community-based annual health checkup examinees), and controlling forthe confounding effects of the socioeconomic status (adjusted vs unadjusted). The
present study attempted to reduce the degree of selection bias and potential confounding
effects as much as possible. In contrast, both studies included a limited number ofmortality events during relatively short periods of time, namely 3–5 years. Thus, further

12

long-term follow-up studies are warranted to elucidate the association between the dailyfrequency of laughter and onset of mortality.
The primary strengths of the present study are its prospective cohort design,nlarge sample size, population-based sampling, and control for potential confoundingsiofactors. In contrast, a limitation of the study was that we evaluated the daily frequencyof laughter using a single-item self-reported question. The perceived frequency oflaughter may be different from the actual frequency; hence, it may be plausible that lessVerhealthy individuals are more likely to not report their frequency of laughter, possibly
leading to an underestimation of the association between laughter and health outcomes.
Additionally, it is unclear whether laughter itself can prevent the onset of functionaleddisability and mortality. Therefore, further studies are required to precisely identify thecausal inference using observational data34 because random assignment of the dailyptfrequency of laughter and long-term follow-up of the randomized participants to collectthe data on number of onset events are difficult in the real-world setting.

ce

In conclusion, the present study revealed that community-dwelling older

Japanese who do not laugh much in daily life are at a higher risk of the onset ofAc

functional disability, suggesting that the frequency of laughter is potentially considered
an early indicator of late-life functional disability.

13

Acknowledgments
We are grateful to the subjects who participated in this study and to Ichiro Kawachi
from Harvard T.H. Chan School of Public Health for his useful commnets.

n

Conflicts of Interests: Authors declared no competing interests for this article.

sioFunding sources: This study used data from JAGES (the Japan Gerontological
Evaluation Study). This study was supported by Grant-in-Aid for Scientific Research(15H01972, 15H04781, 15H05059, 15K03417, 15K03982, 15K16181, 15K17232,

Ve
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15K18174, 15K19241, 15K21266, 15KT0007, 15KT0097, 16H05556, 16K09122,
16K00913, 16K02025, 16K12964, 16K13443, 16K16295, 16K16595, 16K16633,
16K17256, 16K17281, 16K19247, 16K19267, 16K21461, 16K21465, 16KT0014,

ed

17K04305, 17K34567, 17K04306, 25253052, 25713027, 26285138, 26460828,
26780328, 18H03018, 18H04071, 18H03047, 18H00953, 18H00955, 18KK0057,

pt

19H03901, 19H03915, 19H03860, 19K04785, 19K10641, 19K11657, 19K19818,
19K19455, 19K24060, 19K20909) from JSPS (Japan Society for the Promotion of
HealthLabource

Science);

H27-Ninchisyou-Ippan-001,

Sciences

Research

Grants

H28-Choju-Ippan-002,(H26-Choju-Ippan-006,

H28-Ninchisyou-Ippan-002,

Ac

H29-Chikyukibo-Ippan-001, H30-Jyunkankinado-Ippan-004, 18H04071, 19FA1012,
19FA2001) from the Ministry of Health, Labour and Welfare, Japan; the Research andDevelopment Grants for Longevity Science from Japan Agency for Medical Researchanddevelopment(AMED)(JP17dk0110027,

JP18dk0110027,

JP18ls0110002,

JP18le0110009, JP19dk0110034, JP19dk0110037), the Research Funding for Longevity
Sciences from National Center for Geriatrics and Gerontology (20-19, 24-17, 24-23,
29-42, 30-30, 30-22) ; Open Innovation Platform with Enterprises, Research Instituteand Academia (OPERA，JPMJOP1831) from the Japan Science and Technology (JST);14

a grant from the Japan Foundation For Aging And Health （J09KF00804）, a grant from
Innovative Research Program on Suicide Countermeasures (1-4), a grant from
Sasakawa Sports Foundation, a grant from Japan Health Promotion & FitnessnFoundation, a grant from Chiba Foundation for Health Promotion & Disease Prevention,siothe 8020 Research Grant for fiscal 2019 from the 8020 Promotion Foundation (adopted
number: 19-2-06), a grant from Niimi University (1915010), grants from Meiji YasudaVerLife Foundation of Health and Welfare. The views and opinions expressed in this article
are those of the authors and do not necessarily reflect the official policy or position of

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ce

pt

ed

the respective funding organizations.

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Epidemiol. 2016;44(5):409-415. doi:10.1111/cdoe.12231

20

Tables
Table 1. Baseline Characteristics of the Study Population by the frequency of laughter
1-3 days permonth(n = 1639)

Never or
Almostnever(n = 1034)

n

%

n

%

n

%

n

%

3417

55.8

2700

49.6

603

36.8

351

33.9

Age , yrs
1925

31.5

1683

30.9

468

70-74

2078

34.0

1632

30.0

465

75-79

1245

20.3

1198

22.0

80-84

616

10.1

651

< 85

256

4.2

276

Hypertension
2779

Diabetes mellitus
Smoking habit

Ever

25.3

28.4

293

28.3

387

23.6

220

21.3

12.0

220

13.4

155

15.0

5.1

99

6.0

104

10.1

2487

45.7

13.5

740

745

45.5

483

<0.001

13.6

254

15.5

189

18.3
<0.001a

571

9.3

554

10.2

229

14.0

175

16.9

903

998

18.3

363

22.1

229

22.1

4646

75.9

3888

71.5

1047

63.9

630

60.9

Current

2138

34.9

1995

36.7

677

41.3

393

38.0

Ever

262

4.3

282

5.2

113

6.9

74

7.2

Never

3720

60.8

3163

58.1

849

51.8

567

54.8

<0.001aAc

Alcohol Intake<0.001a

Family structure
Alone

679

11.1

890

16.4

314

19.2

261

25.2

>2 without partner

793

13.0

722

13.3

189

11.5

147

14.2

>2 with partner>2 without information
about marital status
Social participation

4608

75.3

3787

69.6

1118

68.2

614

59.4

40

0.7

41

0.8

18

1.1

12

1.2

Active<0.001a

46.7

14.8

Never

<0.0010.537

ce

Current827

pt

Diagnosed

45.4

262

ed

Diagnosed

28.6

Ve
r

65-69

p for
trend

n

1-5 days perweek(n = 5440)

si
o

Women

Almost everyday(n = 6120)<0.001
2186

35.7

1816

33.4
21

368

22.5

151

14.6

Depressive symptoms<0.001

Depressed

872

14.2

1416

26.0

672

41.0

618

59.8

Cognitive function<0.001
1871

30.6

1905

35.0

690

51.1

16.2

1018

18.7

391

3835

62.7

3288

60.4

23.9

1004

23.5

1476

27.1

520

1.50-1.99

1285

21.0

1296

23.8

2.00-2.49

1181

19.3

979

2.50-2.99

364

5.9

3.00-3.49643

3.50-3.99398

4.00-4.49

156

4.50-4.99

193> 5.00

461

61.3

332

32.1

538

425

41.1

406

24.8

228

22.1

18.0

303

18.5

158

15.3

330

6.1

72

4.4

49

4.7

10.5

506

9.3

107

6.5

51

4.9

6.5

308

5.7

93

5.7

43

4.2

2.5

99

1.8

27

1.6

17

1.6

3.2

148

2.7

33

2.0

22

2.1

7.5

298

5.5

78

4.8

41

4.0

ed

pt

Tested using chi-square test.

Ac
22<0.001

52.0

31.7

Ve
r

1439

n

993

ce

a

528

<0.001

Attainment of education> 10 years
Equivalent income(10,000$, 1$ = 100yen)< 1.4942.1

sioDeclineInstrumental activities ofdaily living
Dependent<0.001aTable 2. Likelihood of onset of functional disability and all-cause mortality according to thefrequency of laughternNever or
Almost never(n = 1034)
98
2.98(2.34-3.79)
2.14(1.68-2.74)
1.42(1.10-1.85)85
2.29(1.79–2.94)
1.52(1.18-1.96)
1.08(0.83-1.41)sio

1-3 days permonth(n = 1639)
78
1.45(1.12-1.88)
1.22(0.94-1.59)
0.97(0.74-1.27)
104
1.75(1.38–2.20)
1.35(1.07-1.70)
1.13(0.89-1.44)

p for
trend

<0.001<0.001
0.039<0.001<0.001
0.389

ed

Ve
r

Almost every 1-5 days perday
week(n = 6120)(n = 5440)
Functional disability, n
206
223
1.00
1.23
Crude HR (95% CI)(reference)(1.02-1.49)
Adjusted HR (95%
1.00
1.13
CI)a
(reference)(0.94-1.37)
Adjusted HR (95%
1.00
1.04
CI)b
(reference)(0.86-1.26)
All-cause mortality, n
226
244
1.00
1.22
Crude HR (95% CI)(reference)(1.02–1.47)
Adjusted HR (95%
1.00
1.10
a
CI)
(reference)(0.92-1.32)
Adjusted HR (95%
1.00
1.03
b
CI)
(reference)(0.86-1.24)
HR = hazard ratio; CI = confidence interval.
Adjusted for sex, age.

b

Adjusted for sex, age, hypertension, diabetes mellitus, smoking, alcohol intake, family structure,

pt

a

ce

social participation, depressive symptoms, cognitive function, instrumental activities of daily living,Ac

educational attainment, equivalent income.

23

Figure legends
Figure 1. Kaplan-Meier curves showing cumulative incidence of functional disability (A) and

Ac

ce

pt

ed

Ve
r

si
o

n

all-cause mortality (B) according to the frequency of laughter24Figure 1.

ed

pt

ce

Ac

on

si

Ve
r