Short Daytime Napping Reduces the Risk of Cognitive Decline in Community-Dwelling Elderly Individuals: a 5-Year Longitudinal Study

Short Daytime Napping Reduces the Risk of Cognitive Decline in Community-Dwelling Elderly Individuals: a 5-Year Longitudinal Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Short Daytime Napping Reduces the Risk of Cognitive Decline in Community-Dwelling Elderly Individuals: a 5-Year Longitudinal Study Kaori Kitamura, Yumi Watanabe, Kazutoshi Nakamura, Chikako Takano, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-208747/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Beneficial effects of napping on cognition have been suggested in cross-sectional studies. This study aimed to clarify longitudinal associations between cognitive decline and sleep characteristics, particularly daytime napping, over a 5-year period in older adults. Methods: Study participants were 389 community-dwelling individuals aged ≥65 years living in Ojiya City, Niigata, Japan. Baseline and follow-up examinations were conducted in 2011-2013 and 2016-2018, respectively. Trained nurses visited and interviewed participants to collect the following information: demographic characteristics, disease history, lifestyle habits including sleep and daytime napping, and cognitive function at baseline; and cognitive function at follow-up. The assessment of cognitive function was performed using the revised Hasegawa’s dementia scale (HDS-R), with cognitive decline defined as a 5-year change in HDS-R of ≤–3. Odds ratios (ORs) for cognitive decline were calculated using multiple logistic regression analysis. Results: Mean age of participants was 74.6 years (SD 6.4), and the cumulative incidence of cognitive decline was 106/389 (27.3%). The multivariable-adjusted OR for 1-29 min daytime napping was significantly lower compared to that for no napping (OR=0.47, 95%CI: 0.23-0.96). Bedtime was inversely associated with cognitive decline (multivariable-adjusted P for trend=0.0480). Conclusion: Short daytime napping (<30 min) reduces the risk of 5-year cognitive decline in community-dwelling older people. A future study will be necessary to confirm the effect of short napping on the reduction of risk for clinically diagnosed dementia. Geriatrics & Gerontology cohort studies napping sleep cognitive decline dementia epidemiology preventive medicine Figures Figure 1 Figure 2 Background Dementia places a tremendous burden on society worldwide. The total number of people with dementia in the world was estimated to be 35.6 million in 2010, and this number is projected to increase to 115.4 million in 2050 [1]. The total cost of dementia is also enormous, estimated at US$ 604 billion in 2010 [1]. Under these circumstances, the prevention of dementia and dementia-related disorders is one of the highest priority issues. The role of sleep in cognitive function and dementia has drawn attention, although evidence is still insufficient [2]. According to recent reviews and meta-analyses, sleep duration and sleep disturbance are determinants of cognitive decline and dementia [3-7]. Moreover, daytime napping is reportedly associated with cognitive function in older adults [8-11]. However, previous study findings have been somewhat inconsistent; some reported possible adverse effects of napping, especially long napping, on cognitive function [9,11], whereas others reported possible beneficial effects of napping, especially short napping [8,10]. Furthermore, except for one longitudinal study [8], only cross-section studies [9-11] have been conducted. More longitudinal studies are awaited to accumulate evidence of higher levels. We previously conducted an epidemiologic study to investigate associations between cognitive impairment and lifestyle factors, including sleep characteristics and daytime napping, in community-dwelling older adults [12]. The present study aimed to clarify longitudinal associations between cognitive decline and sleep characteristics, in particular daytime napping, based on 5-year follow-up data from the participants of study mentioned above. Methods Design and Participants This study was a 5-year follow-up cohort study. Participants at baseline were community-dwelling older adults living in three areas of Ojiya City, Niigata, Japan. Among 592 residents aged ≥65 years receiving no long-term care insurance services who were invited to participate in the study, 535 (90.4%) underwent baseline examination. Of these, 509 participants who were considered cognitively normal were invited to participate in the present 5-year follow-up study, and 371 underwent follow-up examination. We also included 18 individuals who did not participate in the follow-up examination, but were diagnosed with dementia at medical facilities. The final study cohort thus comprised 389 individuals. Figure 1 shows the flow of participant enrollment. Informed consent was obtained from all participants. The consent was verbal because, according to the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan [13], investigators are not required to obtain informed consent in writing for human studies which are not invasive or do not involve interventions. The protocol of this study was approved by the Ethics Committee of Niigata University. Baseline examination The baseline examination was conducted in three areas of Ojiya city in 2011 (Heisei-cho), 2012 (Matto), and 2013 (Katakai). Trained nurses visited and interviewed participants to collect the following information: demographic characteristics, health status (including cognitive function) and lifestyle, family environment (living with family or alone), current occupational status (unemployed or employed), and histories of hypertension, cerebrovascular disease, and diabetes. Cognitive function was assessed using the revised Hasegawa’s dementia scale (HDS-R) [14]. We also collected information regarding alcohol consumption (classified into five categories: 1) non-drinker, 2) <7 gou (1 gou is equivalent to 180 mL of Japanese sake ), 3) 7-13 gou , 4) 14-20 gou , and 5) ≥21 gou per week) and smoking status (classified into three categories: 1) non-smoker, 2) past smoker, and 3) current smoker). Usual bedtime and sleeping hours were asked and recorded, and the duration of daytime nap was recorded as 1) none, 2) <30 min, 3) 30-59 min, and 4) ≥60 min. The presence of current sleep disturbance and use of sleeping pills were also asked. Details of the baseline examination have been described previously [ 12 ]. Five-year follow-up examination The follow-up examination, including the HDS-R test, was conducted in 2016 (Heisei-cho), 2017 (Matto in), and 2018 (Katakai), in the same manner as in the baseline examination. Assessment of cognitive function The HDS-R, a 30-point test, was used to assess general cognitive function, with a score ≤20 defined as cognitive impairment at baseline. The HDS-R was developed to screen for dementia (sensitivity: 0.90, specificity: 0.82) with a cut-off point of 20/21 [ 1 4]. The HDS-R has been used in East Asian populations [ 1 5, 1 6] and demonstrated to have a diagnostic accuracy similar to that of the MMSE [ 1 7]. One advantage of using the HDS-R over the MMSE is its diagnostic accuracy regardless of education level [ 1 7]. The HDS-R was administered during baseline and follow-up examinations, and change in HDS-R (DHDS-R = [score at follow-up] – [score at the baseline]) was calculated. We used a cutoff of DHDS-R ≤-3 to detect the presence of cognitive decline, referring to the cutoff of DMMSE ≤-3 (30-point test) used in previous studies [ 1 8, 1 9], based on the fact that longitudinal scores of HDS-R and MMSE change in the same direction in community-dwelling individuals [20]. We also considered 18 individuals who had normal cognitive function at baseline and did not participate in the follow-up examination, but were diagnosed with dementia at medical facilities, as having cognitive decline. Statistical methods The χ 2 test was used to test for independence of categorical data for participant characteristics. Cumulative incidence of cognitive decline was calculated and compared according to levels of potential predictor variables by odds ratios (ORs) computed using simple and multiple logistic regression analysis. First, unadjusted, and age- and baseline-HDS-R-adjusted ORs for cognitive decline according to potential predictors were calculated. Second, ORs for cognitive decline according to bedtime, duration of sleep, and duration of nap were calculated, adjusted for age, baseline HDS-R, sex, region (dummy variables), family environment, job status, histories of hypertension, cerebrovascular diseases, and diabetes, alcohol consumption, smoking status, bedtime, duration of sleep, duration of nap (0, 1-29 min and 1, others), presence of sleep disturbance, and use of sleeping pills. SAS statistical software (release 9.1.3, SAS Institute Inc., Cary, NC, USA) was used for data analysis. P<0.05 was considered statistically significant. Results The mean age of participants was 74.6 years (SD 6.4). Table 1 shows the baseline characteristics of participants by sex. Significant sex-based differences were observed in family environment, job status, alcohol consumption, bedtime, and duration of daytime nap. The overall cumulative incidence of cognitive decline was 106/389 (27.3%). Table 2 shows the cumulative incidence, unadjusted ORs, and age- and baseline-HDS-R-adjusted ORs for cognitive decline according to levels of predictor variables. Age was robustly associated with unadjusted ORs for cognitive decline. The age- and baseline-HDS-R-adjusted OR was significantly lower for “1-29 (min)” daytime napping relative to no napping (reference). The multivariable-adjusted OR (adjusted for all other predictors) was significantly lower for “1-29 (min)” daytime napping relative to no napping (OR=0.47, 95%CI: 0.23-0.96) (Figure 2). Bedtime was inversely associated with cognitive decline (multivariable-adjusted P for trend=0.0480), and multivariable-adjusted ORs were 1.29 (95%CI: 0.55-3.04) for “9:00-9:59 p.m.,” 0.80 (95%CI: 0.32-2.00) for “10:00-10:59,” and 0.50 (95%CI: 0.18-1.39) for “11:00 p.m.-,” relative to “-8:59 p.m.” (reference). The duration of nighttime sleep was not associated with cognitive decline (multivariable-adjusted P for trend=0.7540), and multivariable-adjusted ORs were 1.33 (95%CI: 0.61-2.88) for “<6 hours,” 1.13 (95%CI: 0.57-2.24) for “6-6.9 hours,” 1.55 (95%CI: 0.74-3.26) for “8-8.9 hours,” and 1.47 (95%CI: 0.50-4.35) for “≥9 hours,” relative to “7-7.9 hours” (reference). Sleep disturbance and use of sleeping pills were not associated with cognitive decline (multivariable-adjusted P = 0.8585 and 0.7712, respectively). Discussion This study is the first to report a significant decrease in cognitive decline in older adults who habitually take short daytime naps (<30 min). Cross-sectional studies previously showed associations between daytime napping and cognitive impairment. Cross et al. [ 9 ] reported that longer napping is significantly correlated with increased levels of cognitive deficits in 133 adults aged >50 years. Similarly, Owusu et al. [ 11 ] showed that unintentional, longer naps were correlated with poorer performance on cognitive tests in 2,549 community-dwelling adults aged ≥65 years. While these studies suggested the unfavorable effect of longer napping, shorter napping reportedly had a favorable effect on cognitive performance [ 2 1]. In a cross-sectional study in clinical settings, Asada et al. [ 2 1] found that napping for up to 60 min, but not more than 60 min, was protective against the development of Alzheimer’s disease. Lin et al. [ 10 ] conducted a large-scale cross-sectional study in 10,740 Chinese older adults (≥60 years) and found that short nappers (<30 min) had a significantly lower prevalence of cognitive impairment as assessed by the MMSE compared to no nappers and long nappers (≥30 min). Our findings are consistent with this report. To date, only one longitudinal study of up to 10 years has been conducted [ 8 ], which reported that the risk of MMSE-assessed cognitive impairment was significantly lower in those who habitually take naps, regardless of duration, in a UK cohort. The discrepancy between their findings and ours may be due to the different definitions of cognitive impairment; the present study used a decrease in HDS-R score of ≤3 points to define cognitive impairment, whereas Keage et al. [ 8 ] used newly diagnosed cognitive impairment according to MMSE scores. It is also possible that factors such as the difference in ethnicity might have played a role. A number of studies have reported on the physiologically beneficial effects of napping on cognitive performance in adults [ 2 2, 2 3]. One study even suggested that napping leads to improved cognitive performance in older adults [ 2 4]. However, specific effects of short naps are not fully understood. Short naps (<30 min) reportedly improved cognitive performance and alertness and were associated with less sleep inertia [ 2 2, 2 4]. Moreover, an epidemiologic study has shown that short naps, but not long naps, had a protective effect against cardiovascular risk [ 2 3], suggesting that short naps have stress-releasing effects. These findings suggest that short naps might also be beneficial for cognitive function, since cognitive decline and dementia are considered stress-related conditions/diseases [2 5 , 2 6]. The present study did not find a significant association between the duration of night sleep and the risk of cognitive decline, although longer sleep groups (“8-8.9-hour” and “≥9-hour” groups) tended to have a higher risk of cognitive decline. These findings are in line with the current knowledge [ 3-7 ]. In the present study, earlier bedtime was associated with a higher risk of cognitive decline (multivariable-adjusted P for trend=0.0480). While evidence is scarce, a large cohort study [27] found no association between bedtime and the risk of dementia, although that study only classified bedtime as early or later than 11 PM. Dementia patients reportedly go to bed early [28], and thus, the effect of bedtime on cognition warrants further examination. The present study has several strengths. First, we used a cohort study design, which is preferable for detecting a causal association. Second, this study had a high participation rate at baseline (90.4%) and an acceptable follow-up rate (72.9%). Finally, the information regarding participant lifestyle was obtained and confirmed through interviews during home visits by experienced nurses. There are also some limitations in this study. First, we obtained the participants’ sleep-related information through interviews by trained nurses, but the information was based on their self-report. Therefore, there is a possible misclassification bias, which might have led to underestimation of associations between predictors and outcomes. Second, we did not collect information on naptime, although the timing of naps is also an important factor related to cognitive function [ 2 4]. Naptime, as well as nap duration, could influence sleep quality at night, which in turn could affect cognitive function. Conclusion Short daytime napping (<30 min) reduces the risk of 5-year cognitive decline in community-dwelling older adults. A future study will need to determine whether or not short naps decrease the risk of clinically diagnosed dementia. Abbreviations HDS-R : Hasegawa’s dementia scale ORs : Odds Ratios SD : Standard Deviation CI : Confidence interval Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Niigata University. Informed consent was obtained from all participants. Consent for publication Not applicable. Availability of data and material Data are available to researchers who meet the criteria for access to confidential data. We cannot provide individual data because informed consent to provide data to anyone outside the research group was not obtained from participants. Please contact the corresponding author (principal investigator: Dr. K Nakamura) regarding any requests for access to confidential data. Competing interests The authors have no conflicts of interest to report. Funding Initial of author who received the award: KK. Grant number awarded to the author: Grant of the Kimura Foundation for Nursing Education (2018). URL of the funder’s website: http://www.nurseed.jp/projects/research/index.shtml. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors' contributions All authors contributed to the study conception and design. KK contributed to design and conceptualization, analyzing data, drafting the manuscript, and revising the manuscript for intellectual content. KN contributed to design and conceptualization, analyzing data, and revising the manuscript for intellectual content. YW and TS contributed to revising the manuscript for intellectual content. CT, NH, and HS contributed to design and conceptualization and data collection. All authors read and approved the final manuscript. Acknowledgements We thank the staff of Ojiya City Office who helped us with data collection. This work was supported in part by the Niigata Institute for Traumatic Stress (Mental Health and Welfare Association in Niigata Prefecture) and a grant of the Kimura Foundation for Nursing Education. We used the supercomputer at ACCMS, Kyoto University. References International WHOaAsD. (2012). Dementia: a public health priority. World Health Organization. Geneva (Switzerland). Livingston, G., Sommerlad, A., Orgeta, V., et al. (2017). 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Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping. J Sleep Res, 18 (2), 272-281. Machado, A., Herrera, A. J., de Pablos, R. M., et al. (2014). Chronic stress as a risk factor for Alzheimer's disease. Rev Neurosci, 25 (6), 785-804. Greenberg, M. S., Tanev, K., Marin, M. F., & Pitman, R. K. (2014). Stress, PTSD, and dementia. Alzheimers Dement, 10 (3 Suppl), S155-165. Bokenberger, K., Strom, P., Dahl Aslan, A. K., Johansson, A. L., Gatz, M., Pedersen, N. L., & Akerstedt, T. (2017). Association Between Sleep Characteristics and Incident Dementia Accounting for Baseline Cognitive Status: A Prospective Population-Based Study. J Gerontol A Biol Sci Med Sci, 72 (1), 134-139. Harris, M., & Grando, V. (2014). When is nighttime? A description of bedtime in persons with dementia in the nursing home. Geriatr Nurs, 35 (6), 474-478. Tables TABLE 1. Participant characteristics at baseline. Characteristics Men (n=159) Women (n=230) P value Age (years) 65-69 39 -24.50% 58 -25.20% 0.9955 70-79 83 -52.20% 117 -50.90% 80-89 35 -22.00% 52 -22.60% 90-99 2 -1.30% 3 -1.30% Area of residence Heisei-cho 40 -25.20% 63 -27.40% 0.8174 Matto 67 -42.10% 98 -42.60% Katakai 52 -32.70% 69 -30.00% Family environment Living with family 153 -96.20% 206 -89.60% 0.0155 Living alone 6 -3.80% 24 -10.40% Job status Employed 84 -52.80% 52 -22.60% <0.0001 Unemployed 75 -47.20% 178 -77.40% History of hypertension Absent 82 -51.60% 116 -50.40% 0.8254 Present 77 -48.40% 114 -49.60% History of cerebrovascular disease Absent 150 -94.30% 224 -97.40% 0.1244 Present 9 -5.70% 6 -2.60% History of diabetes Absent 146 -91.80% 210 -91.30% 0.8565 Present 13 -8.20% 20 -8.70% Alcohol consumption*( gou /wk) Non-drinker 41 -25.80% 167 -72.60% <0.0001 <7 21 -13.20% 37 -16.10% 7-13 36 -22.60% 22 -9.60% 14-20 41 -25.80% 3 -1.30% ≥21 20 -12.60% 1 -0.40% Smoking Non-smoker 53 -33.30% 224 -97.40% <0.0001 Past smoker 60 -37.70% 2 -0.90% Current smoker 46 -28.90% 4 -1.70% Bedtime -8:59 p.m. 27 -17.00% 18 -7.80% <0.0001 9:00-9:59 p.m. 62 -39.00% 54 -23.50% 10:00-10:59 p.m. 39 -24.50% 79 -34.30% 11:00 p.m.- 31 -19.50% 79 -34.30% Duration of nighttime sleep (hr) <6 23 -14.50% 48 -20.90% 0.1437 6-6.9 38 -23.90% 65 -28.30% 7-7.9 52 -32.70% 73 -31.70% 8-8.9 35 -22.00% 32 -13.90% ≥9 11 -6.90% 12 -5.20% Duration of daytime nap (min) 0 52 -32.70% 101 -43.90% 0.0098 1-29 35 -22.00% 63 -27.40% 30-59 39 -24.50% 35 -15.20% ≥60 33 -20.80% 31 -13.50% * Equivalent to Japanese sake (1 gou of sake is equivalent to 180 mg sake or 27g ethanol) TABLE 2. Cumulative incidence and odds ratios (ORs) for cognitive decline * according to levels of predictor variables Predictors Cumulative incidence Unadjusted OR (95% CI) Adjusted OR ** (95% CI) Age (years) P for trend<0.0001 65-69 12/97 (12.4%) 1 (Ref) - 70-79 46/200 (23.0%) 2.12 (1.06-4.21) - 80-89 45/87 (51.7%) 7.59 (3.63-15.85) - 90-99 3/5 (60.0%) 10.62 (1.61-70.22) - Sex Men 46/159 (28.9%) 1 (Ref) 1 (Ref) Women 60/230 (26.1%) 0.87 (0.55-1.36) 0.80 (0.49-1.29) Area of residence Heisei-cho 30/103 (29.1%) 1 (Ref) 1 (Ref) Matto 37/165 (22.4%) 0.70 (0.40-1.23) 0.70 (0.39-1.27) Katakai 39/121 (32.2%) 1.16 (0.65-2.05) 1.14 (0.62-2.09) Family environment Living with family 94/359 (26.2%) 1 (Ref) 1 (Ref) Living alone 12/30 (40.0%) 1.88 (0.87-4.05) 1.81 (0.81-4.03) Job status Employed 23/136 (16.9%) 1 (Ref) 1 (Ref) Unemployed 83/253 (32.8%) 2.40 (1.43-4.03) 1.78 (1.03-3.07) History of hypertension Absent 44/198 (22.2%) 1 (Ref) 1 (Ref) Present 62/191 (32.5%) 1.68 (1.07-2.64) 1.23 (0.76-1.99) History of cerebrovascular disease Absent 101/374 (27.0%) 1 (Ref) 1 (Ref) Present 5/15 (33.3%) 1.35 (0.45-4.05) 1.23 (0.40-3.80) History of diabetes Absent 99/356 (27.8%) 1 (Ref) 1 (Ref) Present 7/33 (21.2%) 0.70 (0.29-1.66) 0.72 (0.29-1.77) Alcohol consumption *** ( gou /wk) P for trend=0.3590 P for trend=0.7898 Non-drinker 64/208 (30.8%) 1 (Ref) 1 (Ref) <7 13/58 (22.4%) 0.65 (0.33-1.29) 0.71 (0.34-1.45) 7-13 11/58 (19.0%) 0.53 (0.26-1.08) 0.70 (0.33-1.48) 14-20 11/44 (25.0%) 0.75 (0.36-1.58) 0.95 (0.43-2.09) ≥21 7/21 (33.3%) 1.13 (0.43-2.92) 1.88 (0.68-5.18) Smoking P for trend=0.2706 P for trend=0.0563 Non-smoker 72/277 (26.0%) 1 (Ref) 1 (Ref) Past smoker 17/62 (27.4%) 1.08 (0.58-2.00) 1.31 (0.67-2.56) Current smoker 17/50 (34.0%) 1.47 (0.77-2.79) 1.94 (0.97-3.87) Bedtime P for trend=0.0698 P for trend=0.1472 -8:59 p.m. 13/45 (28.9%) 1 (Ref) 1 (Ref) 9:00-9:59 p.m. 38/116 (32.8%) 1.20 (0.57-2.54) 1.28 (0.58-2.85) 10:00-10:59 p.m. 33/118 (28.0%) 0.96 (0.45-2.04) 0.93 (0.42-2.09) 11:00 p.m.- 22/110 (20.0%) 0.62 (0.28-1.36) 0.71 (0.30-1.65) Duration of nighttime sleep (hr) P for trend=0.0284 P for trend=0.2737 <6 17/71 (23.9%) 1.00 (0.50-1.97) 1.16 (0.57-2.36) 6-6.9 24/103 (23.3%) 0.96 (0.52-1.78) 1.03 (0.54-1.94) 7-7.9 30/125 (24.0%) 1 (Ref) 1 (Ref) 8-8.9 26/67 (38.8%) 2.01 (1.06-3.81) 1.67 (0.84-3.32) ≥9 9/23 (39.1%) 2.04 (0.80-5.17) 1.73 (0.63-4.76) Duration of daytime nap (min) P for trend=0.1085 P for trend=0.8387 None 44/153 (28.8%) 1 (Ref) 1 (Ref) 1-29 15/98 (15.3%) 0.45 (0.23-0.86) 0.46 (0.23-0.90) 30-59 21/74 (28.4%) 0.98 (0.53-1.82) 0.83 (0.43-1.59) ≥60 26/64 (40.6%) 1.70 (0.92-3.12) 1.11 (0.57-2.15) Sleep disturbance Absent 91/338 (26.9%) 1 (Ref) 1 (Ref) Present 14/50 (28.0%) 1.06 (0.54-2.05) 1.20 (0.60-2.41) Use of sleeping pills No 81/308 (26.3%) 1 (Ref) 1 (Ref) Yes 25/81 (30.9%) 1.25 (0.73-2.14) 1.13 (0.64-2.00) * DHDS-R ≤3 ** Adjusted for age and baseline HDS-R score *** Equivalent to Japanese sake (1 gou of sake is equivalent to 180 ml sake or 27g ethanol) Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 08 Mar, 2021 Reviewer # 3 agreed at journal 04 Mar, 2021 Review # 3 received at journal 04 Mar, 2021 Review # 2 received at journal 03 Mar, 2021 Reviewer # 2 agreed at journal 17 Feb, 2021 Review # 1 received at journal 17 Feb, 2021 Reviewer # 1 agreed at journal 04 Feb, 2021 Reviewers invited by journal 03 Feb, 2021 Editor assigned by journal 01 Feb, 2021 Submission checks completed at journal 01 Feb, 2021 Editor invited by journal 01 Feb, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-208747","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":10385460,"identity":"30968854-90c8-4303-bae1-63b09b26c118","order_by":0,"name":"Kaori Kitamura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYBACCWYQWQHEB4AoAUmGGbcWkNQZhBYJwlpAUoxtEC0QAUJAsp3/4Keb87bJ8R3gPXjgwS+7Ov4GHgOGHzUM7OY4tEgzMzNL5267bSx5gC/hQGJfsoTEAR4Dxp5jDMyWDdi1yAH9AtKSuAGo8kBiD7MEw/03Bgy8DQzMBgdwamH+nTvndj1US72EPMiWv3i0AB3GJp3bcDvBAKQl4cdhCRCDGZ8tks3MZtY5x24bzjwMsqXhuOTGA2wFh2WOSeD0i8T5g49v59Tcluc73mP88cefan65A8wbH76psUnGFWIIAIo6cAQxgONIItmAoBYw+INg2hGpZRSMglEwCoY/AAC/jVfej5EzrwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-1480-5777","institution":"Niigata University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kaori","middleName":"","lastName":"Kitamura","suffix":""},{"id":10385461,"identity":"4fce348f-7574-4640-91eb-2fbd95d8f831","order_by":1,"name":"Yumi Watanabe","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yumi","middleName":"","lastName":"Watanabe","suffix":""},{"id":10385462,"identity":"1fe77802-1614-4a3e-9789-7ee47c953da8","order_by":2,"name":"Kazutoshi Nakamura","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kazutoshi","middleName":"","lastName":"Nakamura","suffix":""},{"id":10385463,"identity":"80be9b37-7d07-4b12-9ed5-a93f69bebe0b","order_by":3,"name":"Chikako Takano","email":"","orcid":"","institution":"Ojiya City Government","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chikako","middleName":"","lastName":"Takano","suffix":""},{"id":10385464,"identity":"08a2cd5f-aab0-4c50-9a86-220fd05a55c5","order_by":4,"name":"Naomi Hayashi","email":"","orcid":"","institution":"Ojiya Cty Government","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Naomi","middleName":"","lastName":"Hayashi","suffix":""},{"id":10385465,"identity":"b8585541-6c8a-4ddb-aa3c-7f8f48d4884e","order_by":5,"name":"Hisami Sato","email":"","orcid":"","institution":"Ojiya City Government","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hisami","middleName":"","lastName":"Sato","suffix":""},{"id":10385466,"identity":"17b7d463-694f-4bca-b9e9-e7bec1388100","order_by":6,"name":"Toshiyuki Someya","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Toshiyuki","middleName":"","lastName":"Someya","suffix":""}],"badges":[],"createdAt":"2021-02-04 13:04:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-208747/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-208747/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":5916036,"identity":"2b9f684e-1a27-4a88-8b05-4eb40747874a","added_by":"auto","created_at":"2021-02-12 18:45:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60119,"visible":true,"origin":"","legend":"Flow chart of participant enrollment.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-208747/v1/654e9314c79ded00c8cd5a57.png"},{"id":5916035,"identity":"8c6a7f25-82e5-4884-8d16-99db90ca4278","added_by":"auto","created_at":"2021-02-12 18:45:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45136,"visible":true,"origin":"","legend":"Odds ratios (ORs) for cognitive decline (∆HDS-R ≤3) over 5 years according to the duration of daytime nap. Individuals taking naps 1-29 minutes in duration had a significantly lower risk of cognitive decline.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-208747/v1/b007cf36de1e90855b9c42ee.png"},{"id":13659624,"identity":"4fa98b2b-8758-4dd2-9b6a-ed0cde21fa39","added_by":"auto","created_at":"2021-09-17 10:20:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":371414,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-208747/v1/787819cd-63b0-46d5-afc1-8e274eb26264.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eShort Daytime Napping Reduces the Risk of Cognitive Decline in Community-Dwelling Elderly Individuals: a 5-Year Longitudinal Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eDementia places a tremendous burden on society worldwide. The total number of people with dementia in the world was estimated to be 35.6 million in 2010, and this number is projected to increase to 115.4 million in 2050 [1]. The total cost of dementia is also enormous, estimated at US$ 604 billion in 2010 [1]. Under these circumstances, the prevention of dementia and dementia-related disorders is one of the highest priority issues.\u003c/p\u003e\n\u003cp\u003eThe role of sleep in cognitive function and dementia has drawn attention, although evidence is still insufficient [2]. According to recent reviews and meta-analyses, sleep duration and sleep disturbance are determinants of cognitive decline and dementia [3-7]. Moreover, daytime napping is reportedly associated with cognitive function in older adults [8-11]. However, previous study findings have been somewhat inconsistent; some reported possible adverse effects of napping, especially long napping, on cognitive function [9,11], whereas others reported possible beneficial effects of napping, especially short napping [8,10]. Furthermore, except for one longitudinal study [8], only cross-section studies [9-11] have been conducted. More longitudinal studies are awaited to accumulate evidence of higher levels.\u003c/p\u003e\n\u003cp\u003eWe previously conducted an epidemiologic study to investigate associations between cognitive impairment and lifestyle factors, including sleep characteristics and daytime napping, in community-dwelling older adults [12]. The present study aimed to clarify longitudinal associations between cognitive decline and sleep characteristics, in particular daytime napping, based on 5-year follow-up data from the participants of study mentioned above.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eDesign and Participants\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was a 5-year follow-up cohort study. Participants at baseline were community-dwelling older adults living in three areas of Ojiya City, Niigata, Japan. Among 592 residents aged \u0026ge;65 years receiving no long-term care insurance services who were invited to participate in the study, 535 (90.4%) underwent baseline examination. Of these, 509 participants who were considered cognitively normal were invited to participate in the present 5-year follow-up study, and 371 underwent follow-up examination. We also included 18 individuals who did not participate in the follow-up examination, but were diagnosed with dementia at medical facilities. The final study cohort thus comprised 389 individuals. Figure 1 shows the flow of participant enrollment. Informed consent was obtained from all participants. The consent was verbal because, according to the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan [13], investigators are not required to obtain informed consent in writing for human studies which are not invasive or do not involve interventions. The protocol of this study was approved by the Ethics Committee of Niigata University.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBaseline examination\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe baseline examination was conducted in three areas of Ojiya city in 2011 (Heisei-cho), 2012 (Matto), and 2013 (Katakai). Trained nurses visited and interviewed participants to collect the following information: demographic characteristics, health status (including cognitive function) and lifestyle, family environment (living with family or alone), current occupational status (unemployed or employed), and histories of hypertension, cerebrovascular disease, and diabetes. Cognitive function was assessed using the revised Hasegawa\u0026rsquo;s dementia scale (HDS-R) [14]. We also collected information regarding alcohol consumption (classified into five categories: 1) non-drinker, 2) \u0026lt;7 \u003cem\u003egou\u003c/em\u003e (1 \u003cem\u003egou\u003c/em\u003e is equivalent to 180 mL of Japanese \u003cem\u003esake\u003c/em\u003e), 3) 7-13 \u003cem\u003egou\u003c/em\u003e, 4) 14-20 \u003cem\u003egou\u003c/em\u003e, and 5) \u0026ge;21 \u003cem\u003egou\u003c/em\u003e per week) and smoking status (classified into three categories: 1) non-smoker, 2) past smoker, and 3) current smoker). Usual bedtime and sleeping hours were asked and recorded, and the duration of daytime nap was recorded as 1) none, 2) \u0026lt;30 min, 3) 30-59 min, and 4) \u0026ge;60 min. The presence of current sleep disturbance and use of sleeping pills were also asked. Details of the baseline examination have been described previously [\u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFive-year follow-up examination \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe follow-up examination, including the HDS-R test, was conducted in 2016 (Heisei-cho), 2017 (Matto in), and 2018 (Katakai), in the same manner as in the baseline examination.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAssessment of cognitive function\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe HDS-R, a 30-point test, was used to assess general cognitive function, with a score \u0026le;20 defined as cognitive impairment at baseline. The HDS-R was developed to screen for dementia (sensitivity: 0.90, specificity: 0.82) with a cut-off point of 20/21 [\u003ca href=\"#_ENREF_13\"\u003e1\u003c/a\u003e4]. The HDS-R has been used in East Asian populations [\u003ca href=\"#_ENREF_14\"\u003e1\u003c/a\u003e5,\u003ca href=\"#_ENREF_15\"\u003e1\u003c/a\u003e6] and demonstrated to have a diagnostic accuracy similar to that of the MMSE [\u003ca href=\"#_ENREF_16\"\u003e1\u003c/a\u003e7]. One advantage of using the HDS-R over the MMSE is its diagnostic accuracy regardless of education level [\u003ca href=\"#_ENREF_16\"\u003e1\u003c/a\u003e7]. The HDS-R was administered during baseline and follow-up examinations, and change in HDS-R (DHDS-R = [score at follow-up] \u0026ndash; [score at the baseline]) was calculated. We used a cutoff of DHDS-R \u0026le;-3 to detect the presence of cognitive decline, referring to the cutoff of DMMSE \u0026le;-3 (30-point test) used in previous studies [\u003ca href=\"#_ENREF_17\"\u003e1\u003c/a\u003e8,\u003ca href=\"#_ENREF_18\"\u003e1\u003c/a\u003e9], based on the fact that longitudinal scores of HDS-R and MMSE change in the same direction in community-dwelling individuals [20]. We also considered 18 individuals who had normal cognitive function at baseline and did not participate in the follow-up examination, but were diagnosed with dementia at medical facilities, as having cognitive decline.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical methods\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe \u0026chi;\u003csup\u003e2\u003c/sup\u003e test was used to test for independence of categorical data for participant characteristics. Cumulative incidence of cognitive decline was calculated and compared according to levels of potential predictor variables by odds ratios (ORs) computed using simple and multiple logistic regression analysis. First, unadjusted, and age- and baseline-HDS-R-adjusted ORs for cognitive decline according to potential predictors were calculated. Second, ORs for cognitive decline according to bedtime, duration of sleep, and duration of nap were calculated, adjusted for age, baseline HDS-R, sex, region (dummy variables), family environment, job status, histories of hypertension, cerebrovascular diseases, and diabetes, alcohol consumption, smoking status, bedtime, duration of sleep, duration of nap (0, 1-29 min and 1, others), presence of sleep disturbance, and use of sleeping pills. SAS statistical software (release 9.1.3, SAS Institute Inc., Cary, NC, USA) was used for data analysis. P\u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of participants was 74.6 years (SD 6.4). Table 1 shows the baseline characteristics of participants by sex. Significant sex-based differences were observed in family environment, job status, alcohol consumption, bedtime, and duration of daytime nap.\u003c/p\u003e\n\u003cp\u003eThe overall cumulative incidence of cognitive decline was 106/389 (27.3%). Table 2 shows the cumulative incidence, unadjusted ORs, and age- and baseline-HDS-R-adjusted ORs for cognitive decline according to levels of predictor variables. Age was robustly associated with unadjusted ORs for cognitive decline. The age- and baseline-HDS-R-adjusted OR was significantly lower for \u0026ldquo;1-29 (min)\u0026rdquo; daytime napping relative to no napping (reference).\u003c/p\u003e\n\u003cp\u003eThe multivariable-adjusted OR (adjusted for all other predictors) was significantly lower for \u0026ldquo;1-29 (min)\u0026rdquo; daytime napping relative to no napping (OR=0.47, 95%CI: 0.23-0.96) (Figure 2). Bedtime was inversely associated with cognitive decline (multivariable-adjusted P for trend=0.0480), and multivariable-adjusted ORs were 1.29 (95%CI: 0.55-3.04) for \u0026ldquo;9:00-9:59 p.m.,\u0026rdquo; 0.80 (95%CI: 0.32-2.00) for \u0026ldquo;10:00-10:59,\u0026rdquo; and 0.50 (95%CI: 0.18-1.39) for \u0026ldquo;11:00 p.m.-,\u0026rdquo; relative to \u0026ldquo;-8:59 p.m.\u0026rdquo; (reference). The duration of nighttime sleep was not associated with cognitive decline (multivariable-adjusted P for trend=0.7540), and multivariable-adjusted ORs were 1.33 (95%CI: 0.61-2.88) for \u0026ldquo;\u0026lt;6 hours,\u0026rdquo; 1.13 (95%CI: 0.57-2.24) for \u0026ldquo;6-6.9 hours,\u0026rdquo; 1.55 (95%CI: 0.74-3.26) for \u0026ldquo;8-8.9 hours,\u0026rdquo; and 1.47 (95%CI: 0.50-4.35) for \u0026ldquo;\u0026ge;9 hours,\u0026rdquo; relative to \u0026ldquo;7-7.9 hours\u0026rdquo; (reference). Sleep disturbance and use of sleeping pills were not associated with cognitive decline (multivariable-adjusted P = 0.8585 and 0.7712, respectively).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is the first to report a significant decrease in cognitive decline in older adults who habitually take short daytime naps (\u0026lt;30 min). Cross-sectional studies previously showed associations between daytime napping and cognitive impairment. Cross et al. [\u003ca href=\"#_ENREF_9\"\u003e9\u003c/a\u003e] reported that longer napping is significantly correlated with increased levels of cognitive deficits in 133 adults aged \u0026gt;50 years. Similarly, Owusu et al. [\u003ca href=\"#_ENREF_11\"\u003e11\u003c/a\u003e] showed that unintentional, longer naps were correlated with poorer performance on cognitive tests in 2,549 community-dwelling adults aged \u0026ge;65 years. While these studies suggested the unfavorable effect of longer napping, shorter napping reportedly had a favorable effect on cognitive performance [\u003ca href=\"#_ENREF_20\"\u003e2\u003c/a\u003e1]. In a cross-sectional study in clinical settings, Asada et al. [\u003ca href=\"#_ENREF_20\"\u003e2\u003c/a\u003e1] found that napping for up to 60 min, but not more than 60 min, was protective against the development of Alzheimer\u0026rsquo;s disease.\u003c/p\u003e\n\u003cp\u003eLin et al. [\u003ca href=\"#_ENREF_10\"\u003e10\u003c/a\u003e] conducted a large-scale cross-sectional study in 10,740 Chinese older adults (\u0026ge;60 years) and found that short nappers (\u0026lt;30 min) had a significantly lower prevalence of cognitive impairment as assessed by the MMSE compared to no nappers and long nappers (\u0026ge;30 min). Our findings are consistent with this report.\u003c/p\u003e\n\u003cp\u003eTo date, only one longitudinal study of up to 10 years has been conducted [\u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e], which reported that the risk of MMSE-assessed cognitive impairment was significantly lower in those who habitually take naps, regardless of duration, in a UK cohort. The discrepancy between their findings and ours may be due to the different definitions of cognitive impairment; the present study used a decrease in HDS-R score of \u0026le;3 points to define cognitive impairment, whereas Keage et al. [\u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e] used newly diagnosed cognitive impairment according to MMSE scores. It is also possible that factors such as the difference in ethnicity might have played a role.\u003c/p\u003e\n\u003cp\u003eA number of studies have reported on the physiologically beneficial effects of napping on cognitive performance in adults [\u003ca href=\"#_ENREF_21\"\u003e2\u003c/a\u003e2,\u003ca href=\"#_ENREF_22\"\u003e2\u003c/a\u003e3]. One study even suggested that napping leads to improved cognitive performance in older adults [\u003ca href=\"#_ENREF_23\"\u003e2\u003c/a\u003e4]. However, specific effects of short naps are not fully understood. Short naps (\u0026lt;30 min) reportedly improved cognitive performance and alertness and were associated with less sleep inertia [\u003ca href=\"#_ENREF_21\"\u003e2\u003c/a\u003e2,\u003ca href=\"#_ENREF_23\"\u003e2\u003c/a\u003e4]. Moreover, an epidemiologic study has shown that short naps, but not long naps, had a protective effect against cardiovascular risk [\u003ca href=\"#_ENREF_22\"\u003e2\u003c/a\u003e3], suggesting that short naps have stress-releasing effects. These findings suggest that short naps might also be beneficial for cognitive function, since cognitive decline and dementia are considered stress-related conditions/diseases [2\u003ca href=\"#_ENREF_24\"\u003e5\u003c/a\u003e,\u003ca href=\"#_ENREF_25\"\u003e2\u003c/a\u003e6].\u003c/p\u003e\n\u003cp\u003eThe present study did not find a significant association between the duration of night sleep and the risk of cognitive decline, although longer sleep groups (\u0026ldquo;8-8.9-hour\u0026rdquo; and \u0026ldquo;\u0026ge;9-hour\u0026rdquo; groups) tended to have a higher risk of cognitive decline. These findings are in line with the current knowledge [\u003ca href=\"#_ENREF_3\"\u003e3-7\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eIn the present study, earlier bedtime was associated with a higher risk of cognitive decline (multivariable-adjusted P for trend=0.0480). While evidence is scarce, a large cohort study [27] found no association between bedtime and the risk of dementia, although that study only classified bedtime as early or later than 11 PM. Dementia patients reportedly go to bed early [28], and thus, the effect of bedtime on cognition warrants further examination.\u003c/p\u003e\n\u003cp\u003eThe present study has several strengths. First, we used a cohort study design, which is preferable for detecting a causal association. Second, this study had a high participation rate at baseline (90.4%) and an acceptable follow-up rate (72.9%). Finally, the information regarding participant lifestyle was obtained and confirmed through interviews during home visits by experienced nurses. There are also some limitations in this study. First, we obtained the participants\u0026rsquo; sleep-related information through interviews by trained nurses, but the information was based on their self-report. Therefore, there is a possible misclassification bias, which might have led to underestimation of associations between predictors and outcomes. Second, we did not collect information on naptime, although the timing of naps is also an important factor related to cognitive function [\u003ca href=\"#_ENREF_23\"\u003e2\u003c/a\u003e4]. Naptime, as well as nap duration, could influence sleep quality at night, which in turn could affect cognitive function.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eShort daytime napping (\u0026lt;30 min) reduces the risk of 5-year cognitive decline in community-dwelling older adults. A future study will need to determine whether or not short naps decrease the risk of clinically diagnosed dementia.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eHDS-R\u003c/strong\u003e: Hasegawa\u0026rsquo;s dementia scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eORs\u003c/strong\u003e: Odds Ratios\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e: Standard Deviation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI\u003c/strong\u003e: Confidence interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Niigata University. Informed consent was obtained from all participants.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eData are available to researchers who meet the criteria for access to confidential data. We cannot provide individual data because informed consent to provide data to anyone outside the research group was not obtained from participants. Please contact the corresponding author (principal investigator: Dr. K Nakamura) regarding any requests for access to confidential data.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authors have no conflicts of interest to report.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eInitial of author who received the award: KK.\u003c/p\u003e\n\u003cp\u003eGrant number awarded to the author: Grant of the Kimura Foundation for Nursing Education (2018).\u003c/p\u003e\n\u003cp\u003eURL of the funder\u0026rsquo;s website: http://www.nurseed.jp/projects/research/index.shtml.\u003c/p\u003e\n\u003cp\u003eThe funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. KK contributed to design and conceptualization, analyzing data, drafting the manuscript, and revising the manuscript for intellectual content. KN contributed to design and conceptualization, analyzing data, and revising the manuscript for intellectual content. YW and TS contributed to revising the manuscript for intellectual content. CT, NH, and HS contributed to design and conceptualization and data collection. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWe thank the staff of Ojiya City Office who helped us with data collection. This work was supported in part by the Niigata Institute for Traumatic Stress (Mental Health and Welfare Association in Niigata Prefecture) and a grant of the Kimura Foundation for Nursing Education. We used the supercomputer at ACCMS, Kyoto University.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eInternational WHOaAsD. (2012). Dementia: a public health priority. World Health Organization. Geneva (Switzerland).\u003c/li\u003e\n\u003cli\u003eLivingston, G., Sommerlad, A., Orgeta, V., et al. (2017). Dementia prevention, intervention, and care. \u003cem\u003eThe Lancet, 390\u003c/em\u003e(10113), 2673-2734.\u003c/li\u003e\n\u003cli\u003eKim, H. B., Myung, S. K., Lee, S. M., \u0026amp; Park, Y. C. (2016). Longer Duration of Sleep and Risk of Cognitive Decline: A Meta-Analysis of Observational Studies. \u003cem\u003eNeuroepidemiology, 47\u003c/em\u003e(3-4), 171-180.\u003c/li\u003e\n\u003cli\u003eWu, L., Sun, D., \u0026amp; Tan, Y. (2018). 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Diagnostic accuracy of mini-mental status examination and revised hasegawa dementia scale for Alzheimer's disease. \u003cem\u003eDement Geriatr Cogn Disord, 19\u003c/em\u003e(5-6), 324-330.\u003c/li\u003e\n\u003cli\u003eHensel, A., Angermeyer, M. C., \u0026amp; Riedel-Heller, S. G. (2007). Measuring cognitive change in older adults: reliable change indices for the Mini-Mental State Examination. \u003cem\u003eJ Neurol Neurosurg Psychiatry, 78\u003c/em\u003e(12), 1298-1303.\u003c/li\u003e\n\u003cli\u003eTaniguchi, Y., Yoshida, H., Fujiwara, Y., Motohashi, Y., \u0026amp; Shinkai, S. (2012). A prospective study of gait performance and subsequent cognitive decline in a general population of older Japanese. \u003cem\u003eJ Gerontol A Biol Sci Med Sci, 67\u003c/em\u003e(7), 796-803.\u003c/li\u003e\n\u003cli\u003eYamamoto, N., Yamanaka, G., Ishikawa, M., et al. (2009). Cardio-ankle vascular index as a predictor of cognitive impairment in community-dwelling elderly people: four-year follow-up. \u003cem\u003eDement Geriatr Cogn Disord, 28\u003c/em\u003e(2), 153-158.\u003c/li\u003e\n\u003cli\u003eAsada, T., Motonaga, T., Yamagata, Z., Uno, M., \u0026amp; Takahashi, K. (2000). Associations between retrospectively recalled napping behavior and later development of Alzheimer's disease: association with APOE genotypes. \u003cem\u003eSleep, 23\u003c/em\u003e(5), 629-634.\u003c/li\u003e\n\u003cli\u003eLovato, N., \u0026amp; Lack, L. (2010). The effects of napping on cognitive functioning. \u003cem\u003eProg Brain Res, 185\u003c/em\u003e, 155-166.\u003c/li\u003e\n\u003cli\u003eFaraut, B., Andrillon, T., Vecchierini, M. F., \u0026amp; Leger, D. (2017). Napping: A public health issue. From epidemiological to laboratory studies. \u003cem\u003eSleep Med Rev, 35\u003c/em\u003e, 85-100.\u003c/li\u003e\n\u003cli\u003eMilner, C. E., \u0026amp; Cote, K. A. (2009). Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping. \u003cem\u003eJ Sleep Res, 18\u003c/em\u003e(2), 272-281.\u003c/li\u003e\n\u003cli\u003eMachado, A., Herrera, A. J., de Pablos, R. M., et al. (2014). Chronic stress as a risk factor for Alzheimer's disease. \u003cem\u003eRev Neurosci, 25\u003c/em\u003e(6), 785-804.\u003c/li\u003e\n\u003cli\u003eGreenberg, M. S., Tanev, K., Marin, M. F., \u0026amp; Pitman, R. K. (2014). Stress, PTSD, and dementia. \u003cem\u003eAlzheimers Dement, 10\u003c/em\u003e(3 Suppl), S155-165.\u003c/li\u003e\n\u003cli\u003eBokenberger, K., Strom, P., Dahl Aslan, A. K., Johansson, A. L., Gatz, M., Pedersen, N. L., \u0026amp; Akerstedt, T. (2017). Association Between Sleep Characteristics and Incident Dementia Accounting for Baseline Cognitive Status: A Prospective Population-Based Study. \u003cem\u003eJ Gerontol A Biol Sci Med Sci, 72\u003c/em\u003e(1), 134-139.\u003c/li\u003e\n\u003cli\u003eHarris, M., \u0026amp; Grando, V. (2014). When is nighttime? A description of bedtime in persons with dementia in the nursing home. \u003cem\u003eGeriatr Nurs, 35\u003c/em\u003e(6), 474-478.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTABLE 1. Participant characteristics at baseline.\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"184\"\u003e\n\u003cp\u003eMen (n=159)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"64\"\u003e\n\u003cp\u003eWomen (n=230)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;P value\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"222\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 65-69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-24.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-25.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.9955\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 70-79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-52.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e117\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-50.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 80-89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-22.00%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-22.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 90-99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-1.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-1.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"222\"\u003e\n\u003cp\u003eArea of residence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Heisei-cho\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-25.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-27.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.8174\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Matto\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-42.10%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-42.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Katakai\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-32.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-30.00%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"222\"\u003e\n\u003cp\u003eFamily environment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Living with family\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e153\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-96.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e206\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-89.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.0155\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Living alone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-3.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-10.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eJob status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Employed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-52.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-22.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Unemployed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-47.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e178\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-77.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"277\"\u003e\n\u003cp\u003eHistory of hypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e82\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-51.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e116\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-50.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.8254\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-48.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e114\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-49.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"277\"\u003e\n\u003cp\u003eHistory of cerebrovascular disease\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e150\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-94.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e224\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-97.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.1244\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-5.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-2.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"222\"\u003e\n\u003cp\u003eHistory of diabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e146\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-91.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e210\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-91.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.8565\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-8.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-8.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"277\"\u003e\n\u003cp\u003eAlcohol consumption*(\u003cem\u003egou\u003c/em\u003e/wk)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Non-drinker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-25.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e167\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-72.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026lt;7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-13.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-16.10%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 7-13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-22.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-9.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp;14-20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-25.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-1.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026ge;21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-12.60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-0.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eSmoking\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Non-smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-33.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e224\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-97.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Past smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-37.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-0.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; Current smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-28.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-1.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eBedtime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; -8:59 p.m.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-17.00%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-7.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 9:00-9:59 p.m.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-39.00%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-23.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 10:00-10:59 p.m.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-24.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-34.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 11:00 p.m.-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-19.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-34.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"277\"\u003e\n\u003cp\u003eDuration of nighttime sleep (hr)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026lt;6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-14.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-20.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.1437\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 6-6.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-23.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-28.30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 7-7.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-32.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-31.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 8-8.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-22.00%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-13.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026ge;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-6.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-5.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"277\"\u003e\n\u003cp\u003eDuration of daytime nap (min)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-32.70%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e101\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-43.90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e0.0098\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 1-29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-22.00%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-27.40%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; 30-59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-24.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-15.20%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026ge;60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e-20.80%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e-13.50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003eEquivalent to Japanese \u003cem\u003esake\u003c/em\u003e (1 \u003cem\u003egou\u003c/em\u003e of \u003cem\u003esake\u003c/em\u003e is equivalent to 180 mg \u003cem\u003esake\u003c/em\u003e or 27g ethanol)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTABLE 2. Cumulative incidence and odds ratios (ORs) for cognitive decline\u003csup\u003e*\u003c/sup\u003e according to levels of predictor variables\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003ePredictors\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003eCumulative incidence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003eUnadjusted OR\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eAdjusted OR\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e(95% CI)\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"214\"\u003e\n\u003cp\u003eP for trend\u0026lt;0.0001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 65-69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e12/97 (12.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 70-79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e46/200 (23.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e2.12 (1.06-4.21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 80-89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e45/87 (51.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e7.59 (3.63-15.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 90-99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e3/5 (60.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e10.62 (1.61-70.22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Men\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e46/159 (28.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Women\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e60/230 (26.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.87 (0.55-1.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.80 (0.49-1.29)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eArea of residence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Heisei-cho\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e30/103 (29.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Matto\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e37/165 (22.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.70 (0.40-1.23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.70 (0.39-1.27)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Katakai\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e39/121 (32.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.16 (0.65-2.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.14 (0.62-2.09)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eFamily environment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Living with family\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e94/359 (26.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Living alone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e12/30 (40.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.88 (0.87-4.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.81 (0.81-4.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003eJob status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Employed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e23/136 (16.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Unemployed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e83/253 (32.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e2.40 (1.43-4.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.78 (1.03-3.07)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"246\"\u003e\n\u003cp\u003eHistory of hypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e44/198 (22.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e62/191 (32.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.68 (1.07-2.64)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.23 (0.76-1.99)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" width=\"246\"\u003e\n\u003cp\u003eHistory of cerebrovascular disease\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e101/374 (27.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e5/15 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.35 (0.45-4.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.23 (0.40-3.80)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eHistory of diabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e99/356 (27.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e7/33 (21.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.70 (0.29-1.66)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.72 (0.29-1.77)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eAlcohol consumption\u003csup\u003e***\u003c/sup\u003e(\u003cem\u003egou\u003c/em\u003e/wk)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003eP for trend=0.3590\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eP for trend=0.7898\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Non-drinker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e64/208 (30.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026lt;7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e13/58 (22.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.65 (0.33-1.29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.71 (0.34-1.45)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 7-13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e11/58 (19.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.53 (0.26-1.08)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.70 (0.33-1.48)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;14-20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e11/44 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.75 (0.36-1.58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.95 (0.43-2.09)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026ge;21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e7/21 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.13 (0.43-2.92)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.88 (0.68-5.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003eSmoking\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003eP for trend=0.2706\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eP for trend=0.0563\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Non-smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e72/277 (26.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Past smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e17/62 (27.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.08 (0.58-2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.31 (0.67-2.56)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Current smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e17/50 (34.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.47 (0.77-2.79)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.94 (0.97-3.87)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003eBedtime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003eP for trend=0.0698\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eP for trend=0.1472\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; -8:59 p.m.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e13/45 (28.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 9:00-9:59 p.m.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e38/116 (32.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.20 (0.57-2.54)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.28 (0.58-2.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 10:00-10:59 p.m.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e33/118 (28.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.96 (0.45-2.04)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.93 (0.42-2.09)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 11:00 p.m.-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e22/110 (20.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.62 (0.28-1.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.71 (0.30-1.65)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eDuration of nighttime sleep (hr)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003eP for trend=0.0284\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eP for trend=0.2737\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026lt;6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e17/71 (23.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.00 (0.50-1.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.16 (0.57-2.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 6-6.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e24/103 (23.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.96 (0.52-1.78)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.03 (0.54-1.94)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 7-7.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e30/125 (24.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 8-8.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e26/67 (38.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e2.01 (1.06-3.81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.67 (0.84-3.32)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026ge;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e9/23 (39.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e2.04 (0.80-5.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.73 (0.63-4.76)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eDuration of daytime nap (min)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003eP for trend=0.1085\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eP for trend=0.8387\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; None\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e44/153 (28.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 1-29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e15/98 (15.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.45 (0.23-0.86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.46 (0.23-0.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; 30-59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e21/74 (28.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e0.98 (0.53-1.82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0.83 (0.43-1.59)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026ge;60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e26/64 (40.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.70 (0.92-3.12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.11 (0.57-2.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eSleep disturbance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e91/338 (26.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e14/50 (28.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.06 (0.54-2.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.20 (0.60-2.41)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"160\"\u003e\n\u003cp\u003eUse of sleeping pills\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; No\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e81/308 (26.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e1 (Ref)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp; Yes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"77\"\u003e\n\u003cp\u003e25/81 (30.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"86\"\u003e\n\u003cp\u003e1.25 (0.73-2.14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1.13 (0.64-2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003e*\u003c/sup\u003eDHDS-R \u0026le;3\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e**\u003c/sup\u003eAdjusted for age and baseline HDS-R score\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e***\u003c/sup\u003eEquivalent to Japanese \u003cem\u003esake\u003c/em\u003e (1 \u003cem\u003egou\u003c/em\u003e of \u003cem\u003esake\u003c/em\u003e is equivalent to 180 ml \u003cem\u003esake\u003c/em\u003e or 27g ethanol)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cohort studies, napping, sleep, cognitive decline, dementia, epidemiology, preventive medicine","lastPublishedDoi":"10.21203/rs.3.rs-208747/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-208747/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Beneficial effects of napping on cognition have been suggested in cross-sectional studies. This study aimed to clarify longitudinal associations between cognitive decline and sleep characteristics, particularly daytime napping, over a 5-year period in older adults. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Study participants were 389 community-dwelling individuals aged ≥65 years living in Ojiya City, Niigata, Japan. Baseline and follow-up examinations were conducted in 2011-2013 and 2016-2018, respectively. Trained nurses visited and interviewed participants to collect the following information: demographic characteristics, disease history, lifestyle habits including sleep and daytime napping, and cognitive function at baseline; and cognitive function at follow-up. The assessment of cognitive function was performed using the revised Hasegawa’s dementia scale (HDS-R), with cognitive decline defined as a 5-year change in HDS-R of ≤–3. Odds ratios (ORs) for cognitive decline were calculated using multiple logistic regression analysis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Mean age of participants was 74.6 years (SD 6.4), and the cumulative incidence of cognitive decline was 106/389 (27.3%). The multivariable-adjusted OR for 1-29 min daytime napping was significantly lower compared to that for no napping (OR=0.47, 95%CI: 0.23-0.96). Bedtime was inversely associated with cognitive decline (multivariable-adjusted P for trend=0.0480).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Short daytime napping (\u0026lt;30 min) reduces the risk of 5-year cognitive decline in community-dwelling older people. A future study will be necessary to confirm the effect of short napping on the reduction of risk for clinically diagnosed dementia.\u003c/p\u003e","manuscriptTitle":"Short Daytime Napping Reduces the Risk of Cognitive Decline in Community-Dwelling Elderly Individuals: a 5-Year Longitudinal Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-12 18:45:40","doi":"10.21203/rs.3.rs-208747/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-03-09T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-03-05T00:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-03-05T00:00:00+00:00","index":3,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThe results for the bedtime predictor in the full MV model as described in the results section \"Bedtime was inversely associated with cognitive decline (multivariable-adjusted P for trend=0.0480), seem incorrect given that in Table 2 the trend and category OR in the age and baseline score adjusted models (p=0.147) and simple model (p=0.698) OR are not significant. There is not one category (ie 1.29 (95%CI: 0.55-3.04) ; 0.80 (95%CI: 0.32-2.00); 0.50 (95%CI: 0.18-1.39) in the MV model that is significant so I don't see how the trend can possibly be significant.\" Please check these results.\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2021-03-04T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\nPlease overwrite this text when adding your comments to the authors.\n\n\nThis is an interesting study showing that short daytime napping is associated with reduced risk of cognitive impairment. The longitudinal design and low dropout over 5yrs are strengths.\nThere are severall limitation, most of which I think can be addressed.\nMethods\nP5, Please explain from where the 592 were selected, was this an unbiased sample? Was 592 thte totality, or was it a selection? I assume some sort of selection given the very high acceptance rate (90%) after invitation (how were they invited?)\nPlease provide specific inclusion and exclusion criteria\n\"Were considered cognitive normal\"; please describe how this conclusion was made\nP6: Duration of followup, it seems that participants were seen annually. This should be described more clearly; and also if there was variation in the duration of followup (mean, SD).\nResults\n\"Bedtime was associated with inversely with cognitive decline\"; this is a bit complicated way of saying that later bed-time was associated with less cognitive decline.\nThe lack of association with duration of sleep was a bit surprising, wasn't it? This could be commendted. Also, as you suggest, there might be an association between napping and nighttime sleep duration; this can be analysed in the data set I think\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests'**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2021-02-18T00:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-02-18T00:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nCOMMENTS\n\nThe authors present a prospective observational study examining the association of self-reported sleep parameters with cognitive decline in a cohort of ~380 older Japanese adults. They report that short daytime naps were associated with a lower risk of cognitive decline, and that earlier bedtime with a higher risk. These are innately quite interesting results and the study has many merits, including prospective design and impressive rate of followup. There are issues with the current draft that diminish potential impact including:\n\nThe most important issue is that cognitive decline is defined as HDS-R change of 3 points or greater. This is a plausible choice and parallels similar cutoffs often used on the MMSE. But the interpretation of results would be more robust if the associations were in the same direction using different cutoffs. I.e. I strongly encourage the authors to do sensitivity analyses, repeating their analyses with cutoff of, say, 2 and also 4 points. If everything goes in the same direction it would increase confidence in the interpretation.\n\nThis author is not a statistician but my understanding is that if an OR confidence interval includes 1, suggests no statistically significant association. I will suggest statistical review to the journal but the authors should address this.\n\nWhere did the patients come from? I.e., was this a clinical or community-acquired sample? Prevalence of cognitive impairment will different between the two types of samples. The paper suggests that these are community-acquired cases -- \"All persons\" in Figure 1 -- but needs to be clarified.\n\nI encourage the authors to consider possible biological mechanisms. For example, there is a theory with increasing supporting evidence that the brain clears amyloid during sleep through the 'glymphatic' system. Perhaps we clear most efficiently with short daytime naps?\n\nAbstract: Need to clarify that EARLIER bedtime associated with cognitive decline, the abstract just says 'bedtime\".\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. 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