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PLOS One logoLink to PLOS One
. 2020 Jul 28;15(7):e0236656. doi: 10.1371/journal.pone.0236656

Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

Yu Mon Saw 1,2,*, Thu Nandar Saw 3, Thet Mon Than 1,4, Moe Khaing 1,4, Pa Pa Soe 5, San Oo 6, Su Myat Cho 1, Ei Mon Win 7, Aye Myat Mon 4, Etsuko Fuchita 8, Tetsuyoshi Kariya 1,2, Shigemi Iriyama 8, Nobuyuki Hamajima 1
Editor: Gianluigi Forloni9
PMCID: PMC7386565  PMID: 32722689

Abstract

Background

Globally, elderly population with impaired cognitive function, such as dementia, has been accelerating, and Myanmar is no exception. However, cognitive function among elderly in Myanmar has rarely been assessed. This study aimed to identify the rate of cognitive impairment and its risk factors among the elderly in Myanmar.

Methods

This cross-sectional study was conducted at rural health centers in Nay Pyi Taw Union Territory, Myanmar, from December 2018 to January 2019. In total, 757 elderly individuals aged 60 years or over (males: 246 [32.5%], females: 511 [67.5%]) were interviewed using a face-to-face method with a pre-tested questionnaire. Descriptive statistics and multivariable logistic regression analyses were performed.

Results

The rate of impaired cognitive function among participants was 29.9% (males: 23.6%; females: 32.9%). The following participants were more likely to present cognitive impairment: those aged 70–79 years (adjusted odds ratio [AOR] = 1.8; 95% confidence interval [CI]: 1.19–2.70) and 80 years or older (AOR = 3.9; 95% CI: 2.25–6.76); those who were illiterate (AOR = 9.1; 95% CI: 3.82–21.51); and those dependent on family members (AOR = 1.6; 95% CI: 1.04–2.44). The elderly livening with their families and those who reported having good health (AOR = 0.7; 95% CI: 0.44–0.99) were less likely to have cognitive impairment.

Conclusion

Using the HDS-R Myanmar version, this study reported that there out of five elderly participants had cognitive impairment, and its risk factors, altering policy makers that Myanmar needs to prepare for adequate healthcare services and social support for elderly with cognitive impairment. Future research should be performed not only to detect general cognitive impairment but also to differentiate specific cognitive domains impairments among Myanmar elderly. Longitudinal studies are needed to observe the causal and protective factors associated with cognitive impairments in Myanmar.

Introduction

The elderly population with impaired cognitive function has been increasing worldwide and is estimated to reach 131.5 million by 2050 [1,2]. Amid the prolonged life expectancy in Asia, the aged population with cognitive impairment, such as dementia, is estimated to be 22.85 million out of 485.83 million elderly people aged 60 years or older [2,3]. Approximately 60% of the global cognitive impairment (dementia) burden is borne by developing countries; China and India contribute more than 25% of the global burden [4,5]. In India, the prevalence of a range of estimated mild cognitive impairment was between 15% and 33% [6]. In low- and middle-income countries, the proportion of people living with dementia is projected to increase from 58% in 2010 to 63% in 2030, and 71% by 2050 [7].

Numerous socio-demographic, physical, and mental conditions have been found to be associated with cognitive impairment. Older age [8,9], being female [1012], poor marital relationship [10,1315], low educational level in earlier life [16,17], solitary living [10,1315], low level of physical activity [10,1821], chronic tobacco smoking [22], alcohol consumption [23], obesity [24,25], visual impairment [26], hypertension [27], and diabetes mellitus [28,29] are important risk factors for cognitive decline. Meanwhile, high socioeconomic status [30,31]; high level of social activities [13,32]; good nutrition [33]; being free from anxiety, stress [14], or depression [15]; as well as high level of physical activity [1821] have been observed to be protective factors against cognitive impairment.

Age and gender are unmodifiable risk factors for cognitive decline. In the normal aging process, brain volume shrinkage, especially in the prefrontal cortex, which is responsible for memory performance, starts after 40 years of age and a rapid decrease in brain volume has been observed in patients over 70 years of age [34]. Nowadays, the world’s population is aging as advanced medical technological advances increase life expectancy, and age-related cognitive declination has become a major issue. Non-communicable diseases (NCDs) such as hypertension, diabetes mellitus, and obesity due to low physical activity accompany aging [24,25,29,35]. These are responsible for rapid brain aging and cerebral-vascular accidents, provoking the action of pro-inflammatory cytokines with the resultant chronic inflammation and cerebral white matter atrophy leading to cognitive impairment [24,25,34]. Cognitive impairment is also influenced by hormonal changes, and females suffer most, especially after menopause, due to decreased estrogen levels [10,12].

Learning or education, especially in childhood, enhances brain structure and development by increasing brain vascularization, synapse number, and connections, which improve cognitive function [36,37]. Higher education levels are associated with lower cognitive decline as learning creates favorable structures and neurochemical alterations in the brain [36,37]. High socioeconomic status, high physical and social activities, and less dependency are protective factors for cognitive impairments [13,3032]. People with high socioeconomic status generally have more social contact and activities that make them more active, less dependent, and perform higher physical activities leading to slower cognitive decline [13,3032]. Moreover, these people can have good nutrition and can easily access the health services they need, maintaining their health in a good state that can delay cognitive declination [3032].

On the contrary, elderly people living a solitary life and with failed marital status or unhealthy behaviors such as chronic smoking or alcohol consumption had a higher risk of developing cognitive impairments [10,13,15,22]. Elderly individuals who live alone and are widowed, divorced, or separated may have low social contact and activities that can initiate or exacerbate lower mood or depression, the high-risk factor for cognitive impairment [10,1315]. Elderly people leading a lonely life may also harbor risky behaviors such as chronic alcohol drinking or smoking, as there is no family member to control them, which can increase cognitive impairment [10,13,15,22].

The average life expectancy in Myanmar, a Southeast Asian country with a multi-ethnic population of 51.5 million, was 64.7 years, and elderly people aged 65 years and above accounted for 5.6% of the country’s population [38]. Compared with the census data in 1973 and 1983, Myanmar had a larger proportion of an aging population in the 2014 census data. Moreover, the population pyramid is changing from an expanding type to a stationary one [38]. The number of elderly individuals is estimated to increase annually [38]. Meanwhile, the prevalence of non-communicable diseases (NCDs) is increasing, accounting for the major causes of death in 2013 [39]. Health care for the elderly, including a social welfare system, is underdeveloped, and half of the primary caregivers for the elderly are daughters [40]. In addition to the significant impact on society, cognitive impairment is associated with poor prognosis and other comorbidities, such as hypertension and diabetes mellitus [27,28].

Few studies have been performed on the cognitive function assessment among elderly in Myanmar. Assessing cognitive impairment among the Myanmar elderly using the Myanmar-translated version of the Revised Hasegawa’s Dementia Scale (HDS-R) is still lacking. The HDS-R Myanmar version was officially translated by Myanmar and Japanese scientists, and some modifications were made according to the local context [41]. The scale does not include questions assessing the reading and writing ability of the respondents, making it convenient to use for illiterate people and every ethnic group using different languages in Myanmar. Therefore, it can be used as a screening tool to easily detect cognitive impairment among communities even by the basic health staff, which could be quite helpful in Myanmar with limited human resources for health. Age- and sex-specific cognitive functions, as well as the influencing factors, have not yet been reported. This kind of information is extremely useful to plan programs for elderly care, treatment, and prevention of dementia strategies. Therefore, the present study aimed to identify the rate of cognitive impairment and its risk factors among the elderly in Myanmar.

Methods

Study area and participants

This cross-sectional study was conducted at rural health centers (RHCs) in Nay Pyi Taw Union Territory, Myanmar, from December 2018 to January 2019. Nay Pyi Taw Union Territory has two districts, namely, Ottara (North) and Dekkhina (South), each of which has eight townships. The total population of Nay Pyi Taw Union Territory was 1,160,242 in 2014. Of them, 83,747 were aged at least 60 years. Elderly individuals who lived in the study area less than six months, those who were diagnosed with cognitive impairments along with mental and physical disorders (seriously ill), those who did not understand the Myanmar language, and those who were unable to perform simple arithmetic calculation were excluded from the study.

Sampling procedure and data collection

The study was conducted at four townships of Nay Pyi Taw Union Territory, selected by simple random sampling using a lottery method. In total, 11 out of 26 RHCs were selected for data collection from the eight townships, depending on RHC accessibility and availability. The participants were interviewed using a face-to-face method with a pre-tested questionnaire. The questionnaire pre-test was conducted among 150 elderly individuals in Yangon Region. The questionnaire was structured into four sections: 1) socio-demographic characteristics, 2) substance use behaviors, 3) health problems, and 4) assessment of cognitive function. The participants’ height and weight were measured, and body weight was recorded up to the first decimal point. Blood pressure was assessed three times, 15 minutes after interviewing, using the OMRON M6 automated blood pressure monitor. Random blood sugar testing was performed using a glucometer (Medisafe Fit Smile, MS-FR501W, TERUMO). In total, 971 elderly people were invited to participate in this survey. Of them, 811 elderly participants (males: 264 [32.6%], females: 547 [67.4%]) provided written informed consent and agreed to participate in this study. The response rate was 92.5%. After cleaning the data and removing those with missing responses to the dependent and independent variables, 757 elderly participants (males: 246 [32.5%], females: 511 [67.5%]) were considered for the final data analysis.

Study measures

Dependent variable

The Revised Hasegawa’s Dementia Scale (HDS-R) Myanmar version [41] was used to assess the participants’ cognitive impairment. The HDS-R consists of nine questions: Q1, age (1 point); Q2, the date of interview (4 points); Q3, the place of interview (2 points); Q4, ability to repeat three familiar words (3 points); Q5, subtracting 7 from 100 for twice (2 points); Q6, backward repetition of three and four digits (2 points); Q7, recall of the three words memorized in Q4 (6 points); Q8, immediate recall of five objects in pictures shown and hidden (5 points); and Q9, listing of 10 vegetable names (5 points) [41]. The perfect score on the HDS-R is 30 points and a score of 20 points or lower is considered as an indicator of reduced cognitive function. The dependent variable was cognitive impairment, which was dichotomized into “≤20 points” (presence of cognitive impairment) and “≥21 points” (absence of cognitive impairment). The cut-off point, 20/21, was applied based on the evaluation study of HDS-R test reporting 0.90 for sensitivity and 0.82 for specificity [42].

Independent variables

Socio-demographic characteristics, substance use behaviors, and health problems were considered as independent variables. The current age was categorized into three groups (60–69, 70–79, and ≥80) based on the 10-year age intervals. Marital status was categorized into three groups (single, married, and separated/divorced/windowed). Education was divided into three groups according to the educational background of respondents of the elderly: middle school and above, primary school, and only read and write, and illiterate. Family type was categorized into five groups: living alone, nuclear, extended, three generations, and skip generation to learn how family structures affect the cognitive functions of the elderly.

Substance use behaviors were grouped into the following categories: non-users (never use), ex-users, occasional users, and daily users to see the effect on the cognitive functions of respondents. Self-rated health, physical activities, and vision status were divided into two categories. The nutritional status of the elderly may play an important role in impairment of cognitive function. Therefore, body mass index (BMI) was categorized as underweight, normal, overweight, and obese. Hypertension and diabetes mellitus were grouped into two categories according to self-reported and measurement results. The measurement cutoff point of blood pressure was 140/90 mmHg (hypertension: ≥140/90 mmHg) and random blood sugar was 200 mg/dL (diabetes mellitus: ≥ 200 mg/dL).

Statistical analysis

Data analyses were conducted using SPSS 25.0 (IBM SPSS Inc.). Descriptive and chi-squared tests were conducted to examine the socio-demographic status, health problems, and cognitive function scores according to sex. Logistic regression was performed for the association between cognitive impairment and its risk factors. Adjusted odds ratios (AORs) were estimated to assess the strength of the associations using 95% confidence intervals (CIs) for significance testing. In all analyses, the significance level was set at p <0.05 (two-tailed).

Ethical considerations

This study was approved by the Institutional Technical and Ethical Review Board, University of Public Health, Yangon, Myanmar (letter number: UPH-IRB 2018/Research/48, issued on November 30, 2018) and the Ethical Review Committee of Nagoya University Graduate School of Medicine (approval number: 2018–0436, issued on March 3, 2019). The objectives of the study and the questionnaire contents were explained to the participants before their written informed consent was obtained. Research team members helped illiterate participants read the informed consent form. These participants were requested to mark their fingerprint if they understood the content of the informed consent form and agreed to participate in the study. If participants were incompetent to consent, consent was taken from their legal proxies or advance directives. The data were anonymous; data collection and confidentiality of all data were also carefully maintained. A number of study participants were referred to the nearest public hospitals for further investigation and treatment as needed. Furthermore, this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (S1 Appendix).

Results

Table 1 presents the socio-demographic characteristics of the participants. Of the total 757 participants, 246 (32.5%) were males and 511 (67.5%) females, with a mean age of 71.2 (standard deviation [SD] = 7.59) and 69.7 years (SD = 7.30), respectively. More than one-fourth of them were between 60 and 64 years old (20.7% in males and 29.7% in females), whereas only 1.2% (2% in males and 0.8% in females) were aged 90 years and older (p = 0.020). The majority (64.3%) of the participants completed primary education (p <0.001). More than half of the participants were married (51.9%) and lived with their extended families (57.8%), whereas 7.5% (4.1% in males and 9.0% in females) lived alone (p = 0.014). More than two-thirds of the participants (69.4%) reported high levels of physical activities.

Table 1. Socio-demographic characteristic of participants.

Characteristics Total (N = 757) Male (n = 246) Female (n = 511) P-value
N % n % n %
Age 0.020
    60–64 203 26.8 51 20.7 152 29.7
    65–69 185 24.4 63 25.6 122 23.9
    70–74 170 22.5 65 24.4 105 20.5
    75–79 95 12.5 24 9.8 71 13.9
    80–84 68 9.0 26 106 42 8.3
    85–89 27 3.6 12 4.9 15 2.9
    ≥ 90 9 1.2 5 2.0 4 0.8
Education <0.001
    Illiterate 165 21.8 11 4.5 154 30.1
    Primary school 487 64.3 173 70.3 314 61.4
    Middle school 72 9.5 41 16.7 31 6.1
    High school 22 2.9 16 6.5 6 1.2
    University and above 11 1.5 5 20.0 6 1.2
Marital status <0.001
    Single 49 6.5 13 5.3 36 7.0
    Married 393 51.9 183 74.4 210 41.1
    Others 315 41.6 50 20.3 265 51.9
Family type 0.014
    Living alone 56 7.5 10 4.1 46 9.0
    Nuclear 108 14.3 47 19.1 61 11.9
    Extended 438 57.8 144 58.5 294 57.5
    Three generation 113 14.9 32 13.0 81 15.9
    Skip generation 42 5.5 13 5.3 29 5.7
Low physical activities 0.034
    No 232 69.4 158 64.2 367 71.8
    Yes 525 30.6 88 35.8 144 28.2
Place of interview 0.412
    Ngan Sat RHC 60 7.9 26 10.6 34 6.7
    Tha Pyay Pin RHC 97 12.8 26 10.6 71 13.9
    Zee Kone RHC 81 10.7 29 11.8 52 10.2
    Nat Tha Ye RHC 92 12.2 30 12.2 62 12.1
    Taung Po Thar RHC 54 7.2 18 7.3 36 7.0
    Ma Dot Pin RHC 45 5.9 12 4.9 33 6.5
    Baw Di Gone RHC 60 7.9 19 7.7 41 8.0
    Tha Wut Hti RHC 70 9.2 27 11.0 43 8.4
    Nyaung Lont RHC 87 11.5 31 12.6 56 11.0
    Pyi San Aung RHC 49 6.5 11 4.5 38 7.4
    Si Pin Thar Yar RHC 62 8.2 17 6.8 45 8.8  

A chi-square test for the different between males and females. RHC: rural health center.

Table 2 shows the substance use behaviors and health-related characteristics of the participants. Of all the respondents, 13.8% (22% of males and 10% of females) were daily smokers (p <0.001), and 26% (28.9% of males and 24.7% of females) used smokeless tobacco daily (p = 0.024). Among the males, 17.9%, 6.9%, and 1.6% were former, occasional or social, and heavy drinkers (p <0.001), respectively. Approximately one-third of the participants (30.9% of the males and 37.4% of the females) reported that their health was in very poor or poor condition, whereas 34.9% (28.8% of the males and 37.8% of the females) had two or more comorbid diseases. Regarding vision status, 7.3% of the participants (5.3% of the males and 8.2% of the females) reported having poor vision. In assessing the BMI of the participants, 29.1% (28% of the males and 29.5% of the females) were underweight, and 19.6% (17.1% of the males and 20.7% of the females) were obese. Among the males, 67.9% had hypertension, and 19.9% had diabetes mellitus. In females, 57.3% had hypertension, and 21.3% had diabetes mellitus.

Table 2. Substance use behaviors and health-related characteristic of participants.

Characteristics Total (N = 757) Male (n = 246) Female (n = 511) P-value
N % n % n %
Smoking <0.001
    Never smoke 516 68.2 125 50.8 391 76.5
    Ex-smoker 102 13.5 50 20.3 52 10.2
    Occasional smoker 34 4.5 17 6.9 17 3.3
    Daily smoker 105 13.8 54 22.0 51 10.0
Smokeless tobacco use 0.024
    Never use 457 60.4 139 56.5 318 62.2
    Ex-user 27 3.6 15 6.1 12 2.3
    Occasional user 76 10.0 21 8.5 55 10.8
    Daily user 197 26.0 71 28.9 126 24.7
Alcohol drinking <0.001
    Never Drink 684 90.4 181 73.6 503 98.4
    Ex-drinker 52 6.9 44 17.9 8 1.6
    Occasional/social drinker 17 2.2 17 6.9 0 0
    Heavy drinker 4 0.5 4 1.6 0 0
Self-rated health 0.105
    Very poor/poor 267 35.3 76 30.9 191 37.4
    Fair 237 31.3 76 30.9 161 31.5
    Good/very good 253 33.4 94 38.2 159 31.1
No. of comorbidity 0.055
    No. disease 151 19.9 54 22.0 97 19.0
    At least one disease 342 45.2 121 49.2 221 43.2
    Two or more diseases 264 34.9 71 28.8 193 37.8
Vision status 0.254
    Good 371 49.0 128 52.0 243 47.6
     Fair 331 43.7 105 42.7 226 44.2
    Poor 55 7.3 13 5.3 42 8.2
BMI 0.126
    Under weight (11.9–18.4) 220 29.1 69 28.0 151 29.5
    Normal (18.5–22.9) 283 37.3 106 43.1 177 34.6
    Overweight (23.0–24.9) 106 14.0 29 11.8 77 15.2
    Obese (≥25) 148 19.6 42 17.1 106 20.7
Hypertension 0.005
    No 297 39.2 79 32.1 218 42.7
    Yes 460 60.8 167 67.9 293 57.3
Diabetes mellitus 0.654
    No 599 79.1 197 80.1 402 78.7
    Yes 158 20.9 49 19.9 109 21.3  

A chi-square test for the different between males and females. BMI: body mass index

Table 3 presents the HDS-R individual item scores for dementia by age group. The total mean score was 22.4. The highest mean score was found in the age group of 60–64 years (mean = 24.0) followed by 65–69 years (mean = 23.3). The lowest mean score was found in the ≥ 90 years age group (mean = 17.6). The mean scores for temporal orientation, spatial orientation, registration (words), attention/calculation, digit span backward, recall (words), registration (objects), and word fluency were highest in the 60–64 years age group followed by the 65–69 years group.

Table 3. Revised Hasegawa’s Dementia individual item score by age group.

Items Total (N = 757) 60–64 (n = 203) 65–69 (n = 185) 70–74 (n = 170) 75–79 (n = 95) 80–84 (n = 68) 85–89 (n = 27) ≥ 90 (n = 9)
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
Total score 22.4(4.4) 24.0 (3.5) 23.3 (3.9) 22.3 (4.4) 22.3 (4.1) 20.4 (5.0) 19.0 (5.0) 17.6 (4.7)
Age 1.0 (0.2) 0.99 (1.0) 1.0 (0.2) 0.2 (0.2) 1.0 (0.2) 1.0 (0.1) 1.0 (0.1) 1.0 (0.1)
Temporal orientation 2.5 (1.3) 2.83(1.2) 2.7 (1.3) 2.5 (1.4) 2.0 (1.4) 2.3 (1.4) 1.7 (1.3) 2.3 (1.6)
Spatial orientation 1.7 (0.41) 1.9 (0.3) 1.9 (0.2) 1.9 (0.4) 1.7 (0.5) 1.8 (0.6) 1.7 (0.6) 1.9 (0.3)
Registration (words) 2.3 (1.0) 2.3 (1.0) 2.3 (1.0) 2.3 (1.0) 2.2 (1.1) 2.2 (1.1) 1.9 (1.2) 1.9 (1.3)
Attention/Calculation 0.8 (0.9) 0.9 (0.9) 0.9 (0.9) 0.8 (0.9) 0.4 (0.7) 0.6 (0.8) 0.6 (0.8) 0.7 (0.9)
Digit span backward 0.5 (0.7) 0.6 (0.8) 0.5 (0.8) 0.4 (0.7) 0.3 (0.5) 0.3 (0.5) 0.2 (0.5) 0.2 (0.7)
Recall (words) 4.4 (1.8) 4.9 (1.5) 4.6 (1.6) 4.3 (1.9) 4.2 (1.9) 4.0 (2.1) 3.3 (2.0) 2.2 (1.7)
Registration (objects) 4.5 (0.8) 4.6 (0.6) 4.6 (0.8) 4.6 (0.8) 4.3 (0.9) 4.2 (1.1) 4.2 (0.8) 3.4 (1.4)
Word fluency 4.6 (0.9) 4.8 (0.6) 4.7 (0.8) 4.6 (0.9) 4.3 (1.1) 4.1 (1.3) 4.4 (1.3) 4.0 (1.0)

Table 4 lists the multivariate logistic regression analysis results of factors associated with cognitive impairment in both male and female. In bivariate analysis, the following characteristics were positively associated with cognitive impairment: being older than 70 years, female (unadjusted odds ratio [UOR] = 1.6; 95% CI: 1.12–2.25), separated or divorced or widowed (UOR = 2.7; 95% CI: 1.30–5.61), illiterate (UOR = 14.2; 95% CI: 6.45–31.08) or having the ability to only read and write (UOR = 4.4; 95%: CI 2.07–9.24), dependent (UOR = 2.5; 95% CI: 1.78–3.63), and a former substance user (UOR = 1.4; 95% CI: 1.01–1.95). Meanwhile, the following characteristics were negatively associated with cognitive impairment: belonging to any type of nuclear (UOR = 0.3; 95% CI: 0.13–0.52) or extended (UOR = 0.4; 95% CI: 0.25–0.76) or three-generation (UOR = 0.4; 95% CI: 0.20–0.77) or skip-generation family (UOR = 0.4; 95% CI: 0.17–0.94); and being either underweight (UOR = 0.7; 95% CI: 0.45–0.95) or obese (UOR = 0.4; 95% CI: 0.26–0.70).

Table 4. Multivariable logistic regression analysis of factors associated with cognitive impairment among Myanmar elderly (N = 757).

Characteristics OR 95% CI AOR 95% CI
Age
    60–69
    70–79 2.3 (1.63–3.33)*** 1.8 (1.19–2.70)**
    ≥80 4.9 (3.07–7.72)*** 3.9 (2.25–6.76)***
Gender
    Male
    Female 1.6 (1.12–2.25)** 1.1 (0.69–1.73)
Marital status
    Single
    Married 1.1 (0.53–2.31) 1.1 (0.48–2.46)
    Separated/Divorced/Windowed 2.7 (1.30–5.61)**
Education
    Middle school and above
    Only read and write /Primary school 4.4 (2.07–9.24)*** 3.4 (1.56–7.52)**
    Illiterate 14.2 (6.45–31.08)*** 9.1 (3.82–21.51)***
Dependent
    No
    Yes 2.5 (1.78–3.63)*** 1.6 (1.04–2.44)*
Family type
    Living alone
    Nuclear 0.3 (0.13–0.52)*** 0.4 (0.18–0.97)*
    Extended 0.4 (0.25–0.76)** 0.5 (0.27–0.97)*
    Three generation 0.4 (0.20–0.77)** 0.4 (0.21–0.94)*
    Skip generation 0.4 (0.17–0.94)* 0.6 (0.22–1.45)
Alcohol, smoking and smokeless tobacco use
    Non-user (Never use)
    Ex-user 1.4 (1.01–1.95)* 1.3 (0.89–1.88)
    Occasional user 1.6 (0.88–2.89) 1.6 (0.81–3.30)
    Daily user 1.1 (0.27–4.02) 1.2 (0.25–5.47)
Self-rated health
    Very poor/poor/fair
    Good/very good 0.7 (0.53–1.03) 0.7 (0.44–0.99)*
No. of comorbidity
    No. diseases
    At least one disease 1.0 (0.65–1.49) 0.8 (0.49–1.34)
    Two or more diseases 0.9 (0.61–1.45) 0.9 (0.50–1.57)
Low physical activities
    No
    Yes 0.9 (0.66–1.29) 1.3 (0.88–1.90)
Vision status
    Good
    Fair/poor 1.2 (0.85–1.58) 0.8 (0.58–1.21)
BMI §
    Underweight
    Normal 0.7 (0.45–0.95)* 0.9 (0.60–1.41)
    Overweigh 0.8 (0.51–1.35) 1.4 (0.77–2.24)
    Obese 0.4 (0.26–0.70)* 0.8 (0.44–1.40)
Hypertension
    No
    Yes 0.7 (0.54–1.02) 0.9 (0.58–1.29)
Diabetes mellitus
    No
    Yes 0.8 (0.55–1.21) 0.9 (0.57–1.41)

* p<0.05

**p<0.01, p<0.001

§BMI: Underweight (11.9–18.4), Normal (18.5–22.9), Overweigh (23.0–24.9), and Obese (≥25).

†Adjusted for age, gender, marital status, education, dependent, family type, alcohol, smoking and smokeless tobacco use, self-rated health, no. of comorbidity, low physical activities, vision status, BMI, hypertension, and diabetes mellitus.”

According to adjusted analysis, participants who were in the age group of 70–79 (AOR = 1.8; 95% CI: 1.19–2.70) and 80 years or older (AOR = 3.9; 95% CI: 2.25–6.76); who were illiterate (AOR = 9.1; 95% CI: 3.82–21.51) or completed only primary level education (AOR = 3.4; 95% CI: 1.56–7.52), and dependent on family members (AOR = 1.6; 95% CI: 1.04–2.44) were more likely to have cognitive impairment. Meanwhile, participants who belonged to a nuclear (AOR = 0.4; 95% CI: 0.18–0.97), extended (AOR = 0.5; 95% CI: 0.27–0.97), or three-generation family (AOR = 0.4; 95% CI: 0.21–0.94), and who reported being in good health (AOR = 0.7; 95% CI: 0.44–0.99) were less likely to have cognitive impairment (Table 4).

Discussion

This study is the first to examine the rate of impaired cognitive function using the HDS-R and related comorbidities among the elderly in Myanmar. The rate of impaired cognitive function among participants was 29.9% (males: 23.6%, females: 32.9%). The results revealed that female were significantly more likely to develop cognitive impairment than male participants. Participants, 70 years or older, who had a low education level (i.e., who had primary level education or who could only read and write), and who were dependent on their family members were found to be at higher odds of developing cognitive impairment. Meanwhile, participants who lived with their families and who reported being in good health were less likely to develop cognitive impairment.

In this study, the participants older than 70 years had a higher odds of developing cognitive impairment compared with the 60–69 years old age group. This finding is consistent with those of other studies [8,9,27,28]. The rate of cognitive impairment is the highest in the age group of 85 years and older, ranging from 16.7% in China [8] to 43% in Germany [9]. Studies have also estimated that elderly aged 75 years or older account for 80% of patients with dementia [27,28]. Aging is associated with several changes in brain structure and function. Brain volume shrinkage started around or after 40 years, and the shrinkage rate increased especially for those over 70, even in the normal aging process [34]. The most affected area is the prefrontal cortex, which is responsible for memory performance. Reduction in cortical volume associated with increased white matter lesions in the elderly leads to executive function declination and cognitive impairment [34]. Moreover, aging is usually associated with NCDs such as hypertension and type 2 diabetes mellitus [29,35]. Hypertension and diabetes mellitus account for small or large vascular changes leading to cerebral-vascular accidents, strokes, cerebral hemorrhage or micro-cerebral infarcts. As a result, cognitive function impairment is inevitable due to brain volume reduction [29,34,35]. Older age is the greatest unmodifiable risk factor for cognitive impairment [16], and should be taken into consideration in cognitive impairment prevention, as life expectancy is increasing worldwide. Aging can also combine with other comorbidities and can exacerbate the situation [16]. As such, health policymakers and stakeholders in Myanmar should initiate community preventive measures or strategies for cognitive impairment as early as possible to mitigate its adverse consequences.

Participants who had a low educational level (i.e., those who could only read and write or only had primary-level education) were found to be associated with a higher odds of developing cognitive impairment. Numerous studies have pointed out that education has a strong correlation with cognitive impairment; a low educational level in early life is associated with poor cognitive function in both cohort and cross-sectional studies worldwide [1617]. Several mechanisms have been suggested for this correlation. One is that learning or education in early life may affect brain development and structure by enhancing synapse number and connections, as well as by increasing brain blood flow or vascularization, which could enhance cognitive function [36]. Another mechanism is that continuous mental stimulation through learning or education may increase favorable structural or neurochemical alterations in the brain, which in turn improve cognitive function [37]. However, a number of cohort studies did not find associations between low education and cognitive decline [43,44].

Participants who were dependent were more likely to have cognitive impairment. One explanation is that they may have no formal job, leading to a low level of daily physical activities, which is considered to worsen the cognitive performance of the individual [10,1821]. In addition, participants who were dependent were more likely to be cared for by their daughters; half of the caregivers in Myanmar were elderly’ daughters [40]. These participants were considered to have a low level of physical activities; in Myanmar, daughters’ care of their parents are commonly of an over-protective nature. The elderly are considered to be vulnerable to slips and falls owing to aging, and the daughters are more likely to take care of all the daily chores, which may lead to the elderly being physically less active than their independent counterparts, which in turn results in their cognitive decline [10,1821]. Therefore, educational programs in Myanmar for daily physical exercises or activities targeting not only the elderly but also the caregivers will be beneficial.

Participants who lived with their families, either in a nuclear, extended, or three-generation type, were found to have a lower odds of developing cognitive impairment. Studies have also found that elderly who live alone have a much higher risk for developing cognitive impairment compared with elderly living with their families [10,1315]. The elderly living alone are considered to have less social contact, which is associated with increased cognitive decline owing to lower mood and depression, compared with elderly living with family [14,15]. Notably, such a protective association was not observed in the participants who belonged to the skip generation family type in this study. One of the possible reasons is that the elderly experienced much worry and anxiety taking care of their grandchildren when their children were away, especially migrant workers, thereby leading to cognitive decline attributable to stress [14]. As such, a strong social support system that meets the needs of the elderly should be formulated, assessed, and implemented in Myanmar.

Participants who rated their health status as in good or very good condition were also less likely to develop cognitive impairment, compared with those who rated their health status as poor. One explanation may be that these elderly individuals may have a high socio-economic status and easy access to the health services they need, both of which are strong protective factors against cognitive impairment [30,31]. High socio-economic status also means having a high nutritious food intake [31], as well as a high level of social activities or communication in their lives, which have been proven to improve cognitive function [13,32]. Another alternative explanation according to the local context is that the elderly never may have done the necessary health check-up, as they appeared to be healthy, and therefore, they rated their health status as in good condition.

Among the participants, female participants and those either separated, divorced, or widowed had a higher odds of developing cognitive impairment in the unadjusted analysis. Studies have noted that sex plays a role in cognitive functioning [10,11], and females are found to have higher cognitive impairment compared with males [10], or decreased cognitive performance in patients with Alzheimer’s disease [12]. A possible reason may be the hormonal difference and influence between the sexes; the decreased estrogen level in later life has a negative effect on cognitive function in females [12]. Females tend to have a longer life expectancy than males in Myanmar, but this does not necessarily apply for healthy life expectancy [45]. A longer life expectancy with high co-morbidities (i.e., aging with unproductive life) will result in a greater burden for the patient and the caregivers. Therefore, preventive strategies that account for sex differences are highly recommended to reduce the burden of cognitive impairment among Myanmar elderly. In addition, among all participants, those who were either separated, divorced, or widowed had a higher odds of developing cognitive impairment as they may have less social contact or fewer activities within the community, leading to social isolation, which is the greatest risk factor for cognitive impairment [10,1315].

Participants whose BMI was in the normal or obese category were observed to have a lower odds of developing cognitive impairment in this study. Many studies agree that maintaining normal body weight throughout the life span is considered to be a protective factor for cognitive impairment, which is consistent with this study [24,25]. Increased BMI associated with central obesity in the middle years of life has been observed as one of the risk factors for cognitive decline in older age by recent systematic reviews and meta-analyses [24,25]. Obesity in the middle years of life is usually related to hypertension, stroke, diabetes mellitus, and dyslipidemia [24,25,29,35]. Moreover, middle-age obesity is more likely to be associated with rapid brain aging and cerebral white matter atrophy due to the action of pro-inflammatory cytokines causing chronic inflammation and metabolic diseases [24,25,34]. Pathophysiological changes in obesity are considered to be related mainly to adiposity distribution, which cannot be measured directly by BMI as it fails to differentiate muscles from adipose tissues [24,25]. This study used BMI to categorize underweight, normal, overweight, and obese among the participants. This is one of the possible reasons why obese participants in this study had a lower odds of cognitive impairment. Another reason for the lower odds of cognitive impairment among obese participants in this study is that their obesity may start in their late-life as obesity in the later years of life (over 76 years of age) is found to be associated with slower cognitive decline in some studies [24,25].

In this study, 13.8% of the participants were daily smokers and 0.5% were heavy drinkers. Chronic smokers were more likely to be alcohol drinkers, and chronic tobacco smoking is associated with cognitive decline and the development of neurocognitive diseases in later life [22]. However, this association was not found in this study. This may be due to the limited number of study participants and the study conducted in the same demographic area in Myanmar.

This study has several strengths and limitations. This is the first study to investigate the prevalence of impaired cognitive function using the Myanmar-translated version of the HDS-R and its related comorbidities among Myanmar elderly. It was observed that 23.6% of males and 32.9% of females in this study had cognitive impairment detected by the HDS-R. The HDS-R has its own advantages. As it does not include questions assessing the reading and writing ability of respondents, it is convenient to use in illiterate people or in minor ethnic groups who cannot read and write the Myanmar language. Cognitive impairment could be checked easily by basic health staff using the HDS-R. However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist. Therefore, cognitive impairment in specific domains such as executive function, spatial working memory, processing speed, attention, and verbal memory or verbal fluency could not be ruled out regardless of HDS-R allowance to assess cognitive impairment. Furthermore, the fairly wide confidence intervals were observed for some predictors despite the large sample size.

The study was conducted in one region in the central part of Myanmar, which limited the generalizability of the results, given that different socio-demographic features are represented across Myanmar. The causal relationship between cognitive impairment and different risk factors could not be explored clearly owing to the cross-sectional design of the study.

Conclusion

Three out of five elderly participants reported having cognitive impairment and female participants were significantly more likely to develop cognitive impairment. Being over 70 years old, a low educational level, dependency, solitary living, and poor self-rated health were associated with a higher odds of developing cognitive impairment. Meanwhile, living with one’s family and having good self-rated health were protective factors. Based on scientific evidence, policymakers need to consider implementing community preventive measures or strategies regarding cognitive impairment and gender differences as early as possible to mitigate its adverse consequences among Myanmar elderly. Screening for cognitive impairment using the Myanmar language version of the HDS-R should be confirmed by the clinical diagnosis in the further studies so that even the basic health staff can screen for cognitive impairment among the general population at the most basic lever. Therefore, it could be helpful in limited health workforce settings. Future research should be performed not only to detect general cognitive impairment but also to differentiate specific cognitive domains impairments among the Myanmar elderly. Longitudinal studies are needed to observe the causal and protective factors associated with cognitive impairments and associated comorbidities in Myanmar.

Supporting information

S1 Appendix. STROBE (Strengthening the reporting of observational studies in Epidemiology) checklist.

(PDF)

Acknowledgments

The authors would like to express our sincere appreciation to all the health staff from rural health center, Nay Pyi Taw Union Territory and staff from dept. of Medical Services, Ministry of Health and Sports, Nay Pyi Taw, Myanmar for their kind support and active cooperation in this study.

Data Availability

Data are available upon request as a requirement of the Institutional Review Board, University of Public Health, Yangon, Myanmar for researchers who meet the criteria for access to confidential data. Researchers who would like to access to the data must contact Medical Care Division, Department of Medical Services, Office no. (47),Ministry of Health and Sports, Ottara Thiri Township, Ministry Zone, Nay Pyi Taw 15011, Myanmar. Tel: 95-673-411002, Fax: 95-673-411002. Email: medicalcare@mohs.gov.mm.

Funding Statement

This work was supported by Grants‐in‐Aid for Scientific Research (No. 19K19703) from the Ministry of Education, Science, Sports, and Culture of Japan. The funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Decision Letter 0

Gianluigi Forloni

27 Apr 2020

PONE-D-20-03550

Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

PLOS ONE

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Reviewer #1: Summary: The current manuscript investigated the prevalence of cognitive impairment and related comorbidities among Myanmar elderly. The authors show that the prevalence of impaired cognitive functions among participants was from 23% in males to 32 % in females. Authors also evidence that cognitive impairment was associated with age, illiterate, and general health.

Although authors present exciting findings and I would read the final manuscripts, some aspects could be improved.

Please consider the following suggestions for revision:

Introduction: Overall, the introduction provides a broad background and rationale for the research. However, it lacks information on the area of the background relative to the numerous socio-demographic, physical, and mental conditions associated with cognitive impairment. Moreover, the rationale regarding the choice to use the revised Hasegawa's dementia scales for the assessment of cognitive impairment is not clear. More studies evidence that this general test does not always lead to a clear definition of the prevalence. Therefore, it would be appropriate to justify the choice. Finally, the researchers' hypotheses are unclear.

Methods: The method is succinct and comprehensive.

Analysis: the analyses are well conducted. However, it could be useful to define the confounding variables controlled with AORs.

Results: The summary of the study provided is well-defined and fits according to the analysis plan provided. Could it be useful for reporting X2 in the table?

Discussion: This section could be improved, also introducing the specific comments included below.

Some explanations about brain change in the elderly could be helpful to define better why the elderly are more vulnerable to cognitive impairment.

The explanation about BMI is not correct. Recent studies reported a higher risk of occurrence of cognitive impairment in individuals with excessive body weight and high BMI; it could be useful to report these studies and hypothesize a different explanation for this (e.g., non-linear relationship). It is reporting these results to provide a complete view.

Some aspects could be discussed, such as hypertension, behavioral risk factors (alcohol, cigarettes, etc.), and diabetes. All of these are considered as risk factors for cognitive impairment from a lot of studies (and systematic reviews). In particular, to consider that in all samples, 57% of females and 67% of the male are hypertensive.

I suggest the reading of the following systematic review:

“Favieri, F., Forte, G. & Casagrande M. (2019). The executive functions in overweight and obesity: a systematic review of neuropsychological cross-sectional and longitudinal studies. Frontiers in Psychology, 10, 1-27, DOI: 10.3389/fpsyg.2019.02126”;

“Forte, G., De Pascalis, V., Favieri, F., & Casagrande, M. (2020). Effects of Blood Pressure on Cognitive Performance: A Systematic Review. Journal of Clinical Medicine, 9(1), 34” ;

“Cuevas, H. E. (2019). Type 2 diabetes and cognitive dysfunction in minorities: a review of the literature. Ethnicity & health, 24(5), 512-526.”

“Conti, A. A., McLean, L., Tolomeo, S., Steele, J. D., & Baldacchino, A. (2019). Chronic tobacco smoking and neuropsychological impairments: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 96, 143-154.”

“Dye, L., Boyle, N. B., Champ, C., & Lawton, C. (2017). The relationship between obesity and cognitive health and decline. Proceedings of the nutrition society, 76(4), 443-454”.

Regarding limitations, It could be useful reporting the percentage of participants in whom an impairment has been confirmed.

Conclusion: the conclusions appear to be a summary of the results, I suggest reporting the usefulness of this study and further perspective.

General comment: I would also encourage the authors to check all references and to proofread the manuscript to improve the English language.

Reviewer #2: 1. p. 4 - bottom: clarify what you mean by ‘unable to sum the value’.

2. P. 5: please identify how many people were approached to participate in the study, and whether people who refused participation were different from individuals who agreed to participate.

3. Please provide a theoretical justification for choosing the covariates set. Explain why you chose the existing set of covariates instead of other covariates.

4. Justify the decision to stratify the HDS-R instead of treating it as a continuous variable.

5. Cognitive function and impairment can differ across various domains such as working memory, executive function, psychomotor speed, etc. In a study to identify factors associated with cognitive impairment, the examination of specific cognitive domains should be essential. The omission of such an examination is a limitation of a study that purports to seek out risk factors for cognitive impairment.

6. Ethical considerations: please explain how you ensured that study participants with cognitive impairment were capable of providing informed consent.

7. The findings are not novel or surprising, and the choice of variables was not anchored in any sort of theory. As such, the article seemed to be a fishing expedition to find statistically significant results. This is a problem because the wide confidence intervals in the regression analyses suggest the study was underpowered to detect certain effects.

8. Please report the manuscript in accordance with the STROBE guidelines for reporting observational research.

9. Abstract methods: you conducted a ‘multivariable’, not ‘multivariate’, logistic regression analysis.

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2020 Jul 28;15(7):e0236656. doi: 10.1371/journal.pone.0236656.r002

Author response to Decision Letter 0


4 Jun 2020

Response letter (Response to Reviewers)

PONE-D-20-03550: Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

Thank you very much editor and reviewer for your valuable comments and suggestions. We have revised the manuscript according to your suggestions. The revised and edited sentences (and words) are mentioned using a track-changes function in the revised manuscript. We also submitted a clean version of revised manuscript as a separate file. In below responses, we noted reviewer’s comments in black color and our responses in blue color.

Reviewer #1:

Summary: The current manuscript investigated the prevalence of cognitive impairment and related comorbidities among Myanmar elderly. The authors show that the prevalence of impaired cognitive functions among participants was from 23% in males to 32 % in females. Authors also evidence that cognitive impairment was associated with age, illiterate, and general health. Although authors present exciting findings and I would read the final manuscripts, some aspects could be improved. Please consider the following suggestions for revision:

Q-1: Introduction: Overall, the introduction provides a broad background and rationale for the research. However, it lacks information on the area of the background relative to the numerous socio-demographic, physical, and mental conditions associated with cognitive impairment. Moreover, the rationale regarding the choice to use the revised Hasegawa's dementia scales for the assessment of cognitive impairment is not clear. More studies evidence that this general test does not always lead to a clear definition of the prevalence. Therefore, it would be appropriate to justify the choice. Finally, the researchers' hypotheses are unclear.

A-1: Authors’ response: Thank you very much for the comments. As suggested, the information on the area of background relative to the numerous socio-demographic, physical, and mental conditions associated with cognitive impairment were added in the introduction section. The previous second paragraph in the introduction section, “Numerous socio-demographic, physical, and mental conditions have been found to be associated with cognitive impairment. Older age [8,9], being female [10-12], poor marital relationship [10,13-15], low educational level in earlier life [16,17], solitary living [10,13-15], low level of physical activities [10,18-21], underweight [10,22], hypertension [23], and diabetes mellitus [24] are important risk factors for cognitive decline. Meanwhile, high socio-economic status [25,26]; high level of social activities [13,27]; good nutrition [28]; being free from anxiety, stress [14], or depression [15]; as well as high level of physical activities [18–22] have been observed to be protective factors against cognitive impairment.” is revised and read as follows: “Numerous socio-demographic, physical, and mental conditions have been found to be associated with cognitive impairment. Older age [8,9], being female [10-12], poor marital relationship [10,13-15], low educational level in earlier life [16,17], solitary living [10,13-15], low level of physical activity [10,18-21], chronic tobacco smoking [22], alcohol consumption [23], obesity [24,25], visual impairment [26], hypertension [27], and diabetes mellitus [28,29] are important risk factors for cognitive decline. Meanwhile, high socioeconomic status [30,31]; high level of social activities [13,32]; good nutrition [33]; being free from anxiety, stress [14], or depression [15]; as well as high level of physical activity [18–21] have been observed to be protective factors against cognitive impairment.

Age and gender are unmodifiable risk factors for cognitive decline. In the normal aging process, brain volume shrinkage, especially in the prefrontal cortex, which is responsible for memory performance, starts after 40 years of age and a rapid decrease in brain volume has been observed in patients over 70 years of age [34]. Nowadays, the world’s population is aging as advanced medical technological advances increase life expectancy, and age-related cognitive declination has become a major issue. Non-communicable diseases (NCDs) such as hypertension, diabetes mellitus, and obesity due to low physical activity accompany aging [24,25,29,35]. These are responsible for rapid brain aging and cerebral-vascular accidents, provoking the action of pro-inflammatory cytokines with the resultant chronic inflammation and cerebral white matter atrophy leading to cognitive impairment [24,25,34]. Cognitive impairment is also influenced by hormonal changes, and females suffer most, especially after menopause, due to decreased estrogen levels [10,12].

Learning or education, especially in childhood, enhances brain structure and development by increasing brain vascularization, synapse number, and connections, which improve cognitive function [36,37]. Higher education levels are associated with lower cognitive decline as learning creates favorable structures and neurochemical alterations in the brain [36,37]. High socioeconomic status, high physical and social activities, and less dependency are protective factors for cognitive impairments [13,30-32]. People with high socioeconomic status generally have more social contact and activities that make them more active, less dependent, and perform higher physical activities leading to slower cognitive decline [13,30-32]. Moreover, these people can have good nutrition and can easily access the health services they need, maintaining their health in a good state that can delay cognitive declination [30-32].

On the contrary, elderly people living a solitary life and with failed marital status or unhealthy behaviors such as chronic smoking or alcohol consumption had a higher risk of developing cognitive impairments [10,13,15,22]. Elderly individuals who live alone and are widowed, divorced, or separated may have low social contact and activities that can initiate or exacerbate lower mood or depression, the high-risk factor for cognitive impairment [10,13-15]. Elderly people leading a lonely life may also harbor risky behaviors such as chronic alcohol drinking or smoking, as there is no family member to control them, which can increase cognitive impairment [10,13,15,22].” [Introduction, Line 63-102, Page 3-5]

Moreover, the rationale regarding the choice to use the revised Hasegawa’s dementia scale for the assessment of cognitive impairment was also added in the introduction section of the revised manuscript. The last paragraph of the previous introduction section “Few studies have been performed on the cognitive function assessment among elderly in Myanmar. The age- and sex-specific cognitive functions, as well as the influencing factors, are not yet reported. This kind of information is extremely useful to the planning of programs for elderly care, treatment, and prevention of dementia strategies. Therefore, the present study aimed to identify the rate of cognitive impairment and related comorbidities among Myanmar elderly.” was revised as follows: “Few studies have been performed on the cognitive function assessment among elderly in Myanmar. Assessing cognitive impairment among the Myanmar elderly using the Myanmar-translated version of the Revised Hasegawa’s Dementia Scale (HSR-D) is still lacking. The HSR-D Myanmar version was officially translated by Myanmar and Japanese scientists, and some modifications were made according to the local context [41]. The scale does not include questions assessing the reading and writing ability of the respondents, making it convenient to use for illiterate people and every ethnic group using different languages in Myanmar. Therefore, it can be used as a screening tool to easily detect cognitive impairment among communities even by the basic health staff, which could be quite helpful in Myanmar with limited human resources for health. Age- and sex-specific cognitive functions, as well as the influencing factors, have not yet been reported. This kind of information is extremely useful to plan programs for elderly care, treatment, and prevention of dementia strategies. Therefore, the present study aimed to identify the rate of cognitive impairment and its risk factors among the elderly in Myanmar.” [Introduction, Line 114-127, Page 5-6]

To reflect the reviewer’s comments, the previous usage “the prevalence of the cognitive impairment” revised and read as follows: “the rate of cognitive impairment” throughout the revised manuscript.

Q-2: Methods: The method is succinct and comprehensive. Analysis: the analyses are well conducted. However, it could be useful to define the confounding variables controlled with AORs.

A-2: Authors’ response: Thank you very much for your valuable suggestion. As suggested, we added the definition of confounding variables one of the sub-section of methods “Independent variables

Socio-demographic characteristics, substance use behaviors, and health problems were considered as independent variables. The current age was categorized into three groups (60-69, 70-79, and ≥80) based on the 10-year age intervals. Marital status was categorized into three groups (single, married, and separated/divorced/windowed). Education was divided into three groups according to the educational background of respondents of the elderly: middle school and above, primary school, and only read and write, and illiterate. Family type was categorized into five groups: living alone, nuclear, extended, three generations, and skip generation to learn how family structures affect the cognitive functions of the elderly.

Substance use behaviors were grouped into the following categories: non-users (never use), ex-users, occasional users, and daily users to see the effect on the cognitive functions of respondents. Self-rated health, physical activities, and vision status were divided into two categories. The nutritional status of the elderly may play an important role in impairment of cognitive function. Therefore, Body mass index (BMI) was categorized as underweight, normal, overweight, and obese. Hypertension and diabetes mellitus were grouped into two categories according to self-reported and measurement results. The measurement cutoff point of blood pressure was 140/90 mmHg (hypertension: ≥140/90 mmHg) and random blood sugar was 200 mg/dL (diabetes mellitus: ≥ 200 mg/dL).” [Methods, Line 114-127, Page 7-8]

In addition, we also amended the previous footnote of Table 4 “Adjusted for the variables listed in the table.” to read as follows: “Adjusted for age, gender, marital status, education, dependent, family type, alcohol, smoking and smokeless tobacco use, self-rated health, no. of” comorbidity, low physical activities, vision status, BMI, hypertension, and diabetes mellitus. [Results-Table 4, Line 33-36, Page 16]

Q-3: Results: The summary of the study provided is well-defined and fits according to the analysis plan provided. Could it be useful for reporting X2 in the table?

A-3: Authors’ response: Thank you very much for your valuable suggestion. As suggested, we reported Pearson's chi-square test value in the table 1 and 2. [Results Table 1 and 2, Line 217 and 230, Page 11-12]

Table 1 Socio-demographic characteristic of participants

Characteristics Total (N=757) Male (n=246) Female (n=511) X2 ‡

N % n % n %

Age 15.01*

60-64 203 26.8 51 20.7 152 29.7

65-69 185 24.4 63 25.6 122 23.9

70-74 170 22.5 65 24.4 105 20.5

75-79 95 12.5 24 9.8 71 13.9

80-84 68 9.0 26 106 42 8.3

85-89 27 3.6 12 4.9 15 2.9

≥ 90 9 1.2 5 2.0 4 0.8

Education 88.91***

Illiterate 165 21.8 11 4.5 154 30.1

Primary school 487 64.3 173 70.3 314 61.4

Middle school 72 9.5 41 16.7 31 6.1

High school 22 2.9 16 6.5 6 1.2

University and above 11 1.5 5 20.0 6 1.2

Marital status 75.94***

Single 49 6.5 13 5.3 36 7.0

Married 393 51.9 183 74.4 210 41.1

Others 315 41.6 50 20.3 265 51.9

Family type 12.43*

Living alone 56 7.5 10 4.1 46 9.0

Nuclear 108 14.3 47 19.1 61 11.9

Extended 438 57.8 144 58.5 294 57.5

Three generation 113 14.9 32 13.0 81 15.9

Skip generation 42 5.5 13 5.3 29 5.7

Low physical activities 4.50*

No 232 69.4 158 64.2 367 71.8

Yes 525 30.6 88 35.8 144 28.2

Place of interview 10.33

Ngan Sat RHC 60 7.9 26 10.6 34 6.7

Tha Pyay Pin RHC 97 12.8 26 10.6 71 13.9

Zee Kone RHC 81 10.7 29 11.8 52 10.2

Nat Tha Ye RHC 92 12.2 30 12.2 62 12.1

Taung Po Thar RHC 54 7.2 18 7.3 36 7.0

Ma Dot Pin RHC 45 5.9 12 4.9 33 6.5

Baw Di Gone RHC 60 7.9 19 7.7 41 8.0

Tha Wut Hti RHC 70 9.2 27 11.0 43 8.4

Nyaung Lont RHC 87 11.5 31 12.6 56 11.0

Pyi San Aung RHC 49 6.5 11 4.5 38 7.4

Si Pin Thar Yar RHC 62 8.2 17 6.8 45 8.8

RHC: Rural Health Center. ‡Pearson's chi-square test. *p<0.05, **p<0.01, ***p<0.001

Table 2 Substance use behaviors and health-related characteristic of participants

Characteristics Total (N=757) Male (n=246) Female (n=511) X2‡

N % n % n %

Smoking 50.69***

Never smoke 516 68.2 125 50.8 391 76.5

Ex-smoker 102 13.5 50 20.3 52 10.2

Occasional smoker 34 4.5 17 6.9 17 3.3

Daily smoker 105 13.8 54 22.0 51 10.0

Smokeless tobacco use 9.40*

Never use 457 60.4 139 56.5 318 62.2

Ex-user 27 3.6 15 6.1 12 2.3

Occasional user 76 10.0 21 8.5 55 10.8

Daily user 197 26.0 71 28.9 126 24.7

Alcohol drinking 119.37***

Never Drink 684 90.4 181 73.6 503 98.4

Ex-drinker 52 6.9 44 17.9 8 1.6

Occasional/social drinker 17 2.2 17 6.9 0 0

Heavy drinker 4 0.5 4 1.6 0 0

Self-rated health 4.50

Very poor/poor 267 35.3 76 30.9 191 37.4

Fair 237 31.3 76 30.9 161 31.5

Good/very good 253 33.4 94 38.2 159 31.1

Comorbidity 5.81

No disease 151 19.9 54 22.0 97 19.0

At least one disease 342 45.2 121 49.2 221 43.2

Two or more diseases 264 34.9 71 28.8 193 37.8

Vision status 2.74

Good 371 49.0 128 52.0 243 47.6

Fair 331 43.7 105 42.7 226 44.2

Poor 55 7.3 13 5.3 42 8.2

BMI 5.72

Under weight (11.9-18.4) 220 29.1 69 28.0 151 29.5

Normal (18.5-22.9) 283 37.3 106 43.1 177 34.6

Overweight (23.0-24.9) 106 14.0 29 11.8 77 15.2

Obese (=>25) 148 19.6 42 17.1 106 20.7

Hypertension 7.75*

No 297 39.2 79 32.1 218 42.7

Yes 460 60.8 167 67.9 293 57.3

Diabetes mellitus 0.20

No 599 79.1 197 80.1 402 78.7

Yes 158 20.9 49 19.9 109 21.3

‡Pearson's chi-square test. *p<0.05, **p<0.01, ***p<0.001

Q-4: Discussion: This section could be improved, also introducing the specific comments included below. Some explanations about brain change in the elderly could be helpful to define better why the elderly are more vulnerable to cognitive impairment.

A-4: Authors’ response: Thank you very much for the comments. As suggested, we revised the pervious sentences “In this study, the participants who were older than 70 years had a higher risk for developing cognitive impairment compared with the 60–69 years old age group. This finding is consistent with other studies [8,9,23,24]. The rate of cognitive impairment is the highest in the age group of 85 years and older, ranging from 16.7% in China [8] to 43% in Germany [9]. Studies have also estimated that elderly aged 75 years or older account for 80% of patients with dementia [23,24]. Older age is the greatest unmodifiable risk factor for cognitive impairment [16], and should be taken into consideration in cognitive impairment prevention, as life expectancy is increasing worldwide [16]. Aging can also combine with other comorbidities and can exacerbate the situation [16]. As such, health policymakers and stakeholders in Myanmar should initiate community preventive measures or strategies for cognitive impairment as early as possible to mitigate its adverse consequences.” to add more explanations about brain change in the elderly and read as follows: “In this study, the participants older than 70 years had a higher risk of developing cognitive impairment compared with the 60–69 years old age group. This finding is consistent with those of other studies [8,9,27,28]. The rate of cognitive impairment is the highest in the age group of 85 years and older, ranging from 16.7% in China [8] to 43% in Germany [9]. Studies have also estimated that elderly aged 75 years or older account for 80% of patients with dementia [27,28]. Aging is associated with several changes in brain structure and function. Brain volume shrinkage started around or after 40 years, and the shrinkage rate increased especially for those over 70, even in the normal aging process [34]. The most affected area is the prefrontal cortex, which is responsible for memory performance. Reduction in cortical volume associated with increased white matter lesions in the elderly leads to executive function declination and cognitive impairment [34]. Moreover, aging is usually associated with NCDs such as hypertension and type 2 diabetes mellitus [29,35]. Hypertension and diabetes mellitus account for small or large vascular changes leading to cerebral-vascular accidents, strokes, cerebral hemorrhage or micro-cerebral infarcts. As a result, cognitive function impairment is inevitable due to brain volume reduction [29,34,35]. Older age is the greatest unmodifiable risk factor for cognitive impairment [16], and should be taken into consideration in cognitive impairment prevention, as life expectancy is increasing worldwide. Aging can also combine with other comorbidities and can exacerbate the situation [16]. As such, health policymakers and stakeholders in Myanmar should initiate community preventive measures or strategies for cognitive impairment as early as possible to mitigate its adverse consequences.” [Discussion, Line 287-307, Page 17]

Furthermore, the brain changes associated with obesity (BMI and cognitive impairment) was mentioned in the revised paragraph of discussion section as follows: “Moreover, middle-age obesity is more likely to be associated with rapid brain ageing and cerebral white matter atrophy due to the action of pro-inflammatory cytokines causing chronic inflammation and metabolic diseases [23,24,32].” [Discussion, Line 377-379, Page 20]

Q-5: The explanation about BMI is not correct. Recent studies reported a higher risk of occurrence of cognitive impairment in individuals with excessive body weight and high BMI; it could be useful to report these studies and hypothesize a different explanation for this (e.g., non-linear relationship). It is reporting these results to provide a complete view.

Some aspects could be discussed, such as hypertension, behavioral risk factors (alcohol, cigarettes, etc.), and diabetes. All of these are considered as risk factors for cognitive impairment from a lot of studies (and systematic reviews). In particular, to consider that in all samples, 57% of females and 67% of the male are hypertensive.

I suggest the reading of the following systematic review:

“Favieri, F., Forte, G. & Casagrande M. (2019). The executive functions in overweight and obesity: a systematic review of neuropsychological cross-sectional and longitudinal studies. Frontiers in Psychology, 10, 1-27, DOI: 10.3389/fpsyg.2019.02126”;

“Forte, G., De Pascalis, V., Favieri, F., & Casagrande, M. (2020). Effects of Blood Pressure on Cognitive Performance: A Systematic Review. Journal of Clinical Medicine, 9(1), 34” ;

“Cuevas, H. E. (2019). Type 2 diabetes and cognitive dysfunction in minorities: a review of the literature. Ethnicity & health, 24(5), 512-526.”

“Conti, A. A., McLean, L., Tolomeo, S., Steele, J. D., & Baldacchino, A. (2019). Chronic tobacco smoking and neuropsychological impairments: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 96, 143-154.”

“Dye, L., Boyle, N. B., Champ, C., & Lawton, C. (2017). The relationship between obesity and cognitive health and decline. Proceedings of the nutrition society, 76(4), 443-454”.

A-5: Authors’ response: Thank you for your comments. The systematic reviews mentioned by the reviewer were thoroughly read and cited in the revised manuscript. As suggested, the previous paragraph explaining about obesity in the discussion section “Among all participants, those whose BMI was in the normal or obese category were observed to have a lower risk for developing cognitive impairment. A high BMI reflects good nutrition [40] as well as high body fat, which is favorable for increased glucose metabolism, especially cerebral glucose metabolism, which enhanced cognitive performance [41,42]. Studies have also observed that individuals with a low BMI have a higher risk for developing cognitive impairment compared with those with a high BMI [10,22].” was revised and some aspects regarding hypertension, behavioral risk factors (alcohol, cigarettes, etc.), and diabetes were added and to read as follows: “Participants whose BMI was in the normal or obese category were observed to have a lower risk of developing cognitive impairment in this study. Many studies agree that maintaining normal body weight throughout the life span is considered to be a protective factor for cognitive impairment, which is consistent with this study [24,25]. Increased BMI associated with central obesity in the middle years of life has been observed as one of the risk factors for cognitive decline in older age by recent systematic reviews and meta-analyses [24,25]. Obesity in the middle years of life is usually related to hypertension, stroke, diabetes mellitus, and dyslipidemia [24,25,29,35]. Moreover, middle-age obesity is more likely to be associated with rapid brain aging and cerebral white matter atrophy due to the action of pro-inflammatory cytokines causing chronic inflammation and metabolic diseases [24,25,34]. Pathophysiological changes in obesity are considered to be related mainly to adiposity distribution, which cannot be measured directly by BMI as it fails to differentiate muscles from adipose tissues [24,25]. This study used BMI to categorize underweight, normal, overweight, and obese among the participants. This is one of the possible reasons why obese participants in this study had a lower risk of cognitive impairment. Another reason for the lower risk of cognitive impairment among obese participants in this study is that their obesity may start in their late-life as obesity in the later years of life (over 76 years of age) is found to be associated with slower cognitive decline in some studies [24,25].

In this study, 13.8% of the participants were daily smokers and 0.5% were heavy drinkers. Chronic smokers were more likely to be alcohol drinkers, and chronic tobacco smoking is associated with cognitive decline and the development of neurocognitive diseases in later life [22]. However, this association was not found in this study. This may be due to the limited number of study participants and the study conducted in the same demographic area in Myanmar.” [Discussion, Line 370-393, Page 20-21]

Q-6: Regarding limitations, it could be useful reporting the percentage of participants in whom an impairment has been confirmed. Conclusion: the conclusions appear to be a summary of the results, I suggest reporting the usefulness of this study and further perspective.

A-6: Authors’ response: Thank you very much for your comments. As suggested, the percentage of the participants with cognitive impairment was reported in the limitations. The previous limitations sentence, “This study has a number of strengths and limitations. This is the first study to investigate the rate of impaired cognitive function using the Myanmar-translated version of HDS-R and its related comorbidities among Myanmar elderly. HDS-R has its own advantages. As it does not include questions assessing the reading and writing ability of respondents, it is convenient to use in illiterate people or in minor ethnic groups who cannot read and write the Myanmar language. Cognitive impairment could be checked easily by basic health staff using HDS-R. However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist. The study was conducted in one region in the central part of Myanmar, which limited the generalizability of the results, given that different socio-demographic features are represented across Myanmar. The causal relation between cognitive impairment and different risk factors could not be explored clearly owing to the cross-sectional design of the study.” was revised as follows: “This study has several strengths and limitations. This is the first study to investigate the prevalence of impaired cognitive function using the Myanmar-translated version of the HDS-R and its related comorbidities among Myanmar elderly. It was observed that 23.6% of males and 32.9% of females in this study had cognitive impairment detected by the HDS-R. The HDS-R has its own advantages. As it does not include questions assessing the reading and writing ability of respondents, it is convenient to use in illiterate people or in minor ethnic groups who cannot read and write the Myanmar language. Cognitive impairment could be checked easily by basic health staff using the HDS-R. However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist; therefore, cognitive impairment in specific domains such as executive function, spatial working memory, processing speed, attention, verbal memory, or verbal fluency could not be ruled out. The study was conducted in one region in the central part of Myanmar, which limited the generalizability of the results, given that different socio-demographic features are represented across Myanmar. The causal relationship between cognitive impairment and different risk factors could not be explored clearly owing to the cross-sectional design of the study.” [Discussion, Line 394-408, Page 21]

According to the reviewer’s comments, the usefulness of this study and further perspective was reported in the conclusion of the revised manuscript. The previous paragraph in the conclusion section “About 30% of the participants had cognitive impairment and female participants were significantly more likely to develop cognitive impairment compared to male. Being over 70 years old, a low educational level, dependency, solitary living, and poor self-rated health were associated with a higher risk for developing cognitive impairment. Meanwhile, living with one’s family and good self-rated health were protective factors. Policymakers need to consider implementing community preventive measures or strategies regarding cognitive impairment as early as possible to mitigate its adverse consequences.” was revised as follows: “Three out of five elderly participants reported having cognitive impairment and female participants were significantly more likely to develop cognitive impairment. Being over 70 years old, a low educational level, dependency, solitary living, and poor self-rated health were associated with a higher risk of developing cognitive impairment. Meanwhile, living with one’s family and having good self-rated health were protective factors. Based on scientific evidence, policymakers need to consider implementing community preventive measures or strategies regarding cognitive impairment and gender differences as early as possible to mitigate its adverse consequences among Myanmar elderly. Screening for cognitive impairment using the Myanmar language version of the HDS-R should be confirmed by the clinical diagnosis in the further studies so that even the basic health staff can screen for cognitive impairment among the general population at the most basic lever. Therefore, it could be helpful in limited health workforce settings. Future research should be performed not only to detect general cognitive impairment but also to differentiate specific cognitive domains impairments among the Myanmar elderly. Longitudinal studies are needed to observe the causal and protective factors associated with cognitive impairments and associated comorbidities in Myanmar.” [Conclusion: Line 410-424, Page 22]

Furthermore, the previous conclusion section in the abstract “Conclusion: About 30% of participants had cognitive impairment, and female participants were significantly more likely to develop cognitive impairment compared to male participants. Being over 70 years old, having a low educational level, dependency, solitary living, and poor self-rated health were associated with a higher risk for cognitive impairment. Meanwhile, living with families and self-reported good health were protective factors against cognitive impairment.” was also revised into as follows: “Conclusion: Using the HDS-R Myanmar version, this study reported that there out of five elderly participants had cognitive impairment, and its risk factors, altering policy makers that Myanmar needs to prepare for adequate healthcare services and social support for elderly with cognitive impairment. Future research should be performed not only to detect general cognitive impairment but also to differentiate specific cognitive domains impairments among Myanmar elderly. Longitudinal studies are needed to observe the causal and protective factors associated with cognitive impairments in Myanmar.” [Abstract, Line 44-50, Page 2]

Q-7: General comment: I would also encourage the authors to check all references and to proofread the manuscript to improve the English language.

A-7: Authors’ response: Thank you very much for your comments. As suggested, we checked all the references and revised it accordingly. Our manuscript is proofreader by the professional proofreaders with public health experience to improve the language quality of the revised manuscript.

Reviewer #2:

Q-1: p. 4 - bottom: clarify what you mean by ‘unable to sum the value’.

A-1: Authors’ response: Thank you for your question. We corrected the previous word ‘unable to sum the value’ into ‘unable to subtract the value’. We also revised the previous sentence from Materials and Methods section “Elderly individuals who lived in the study area less than six months, who were diagnosed with cognitive impairments along with mental and physical disorders (seriously ill), and who did not understand the Myanmar language and were unable to sum the value were excluded from the study.” to read as follows: “Elderly individuals who lived in the study area less than six months, who were diagnosed with cognitive impairments along with mental and physical disorders (seriously ill), and who did not understand the Myanmar language and were unable to subtract the value were excluded from the study.” [Methods, Line 135-138, Page 6]

Q-2: P. 5: please identify how many people were approached to participate in the study, and whether people who refused participation were different from individuals who agreed to participate.

A-2: Authors’ response: In total, 971 elderly people approached to participate in this study. Elderly individuals who lived in the study area less than six months, who were diagnosed with cognitive impairments along with mental and physical disorders (seriously ill), and who did not understand the Myanmar language and were unable to subtract the value were excluded. As the data collection was collected at rural health centers, the elderly people who would like to voluntarily participate this study came to the rural health centers. The elderly who lived quite far from rural health centers with transportation difficulties, those who were out of town at the time of data collection, and those who had to attend their personal or familial events at the time of data collection refused to participate in this study. As suggested, we added response rate of the survey as follows: “In total, 971 elderly people were invited to participate in this survey. Of them, 811 elderly participants (males: 264 [32.6%], females: 547 [67.4%]) provided written informed consent and agreed to participate in this study. The response rate was 92.5%.” [Methods, Line 150-155, Page 7]

Q-3: Please provide a theoretical justification for choosing the covariates set. Explain why you chose the existing set of covariates instead of other covariates.

A-3: Authors’ response: Thanks for your suggestions. We chose the covariates in our study after thorough literature reviews reporting the risk factors for cognitive impairment, and found those covariates were applicable to study design, local context and the community setting of this study. As suggested, the theoretical justification for choosing the covariates set was mentioned in the revised manuscript as follows: “Numerous socio-demographic, physical, and mental conditions have been found to be associated with cognitive impairment. Older age [8,9], being female [10-12], poor marital relationship [10,13-15], low educational level in earlier life [16,17], solitary living [10,13-15], low level of physical activity [10,18-21], chronic tobacco smoking [22], alcohol consumption [23], obesity [24,25], visual impairment [26], hypertension [27], and diabetes mellitus [28,29] are important risk factors for cognitive decline. Meanwhile, high socioeconomic status [30,31]; high level of social activities [13,32]; good nutrition [33]; being free from anxiety, stress [14], or depression [15]; as well as high level of physical activity [18–21] have been observed to be protective factors against cognitive impairment.

Age and gender are unmodifiable risk factors for cognitive decline. In the normal aging process, brain volume shrinkage, especially in the prefrontal cortex, which is responsible for memory performance, starts after 40 years of age and a rapid decrease in brain volume has been observed in patients over 70 years of age [34]. Nowadays, the world’s population is aging as advanced medical technological advances increase life expectancy, and age-related cognitive declination has become a major issue. Non-communicable diseases (NCDs) such as hypertension, diabetes mellitus, and obesity due to low physical activity accompany aging [24,25,29,35]. These are responsible for rapid brain aging and cerebral-vascular accidents, provoking the action of pro-inflammatory cytokines with the resultant chronic inflammation and cerebral white matter atrophy leading to cognitive impairment [24,25,34]. Cognitive impairment is also influenced by hormonal changes, and females suffer most, especially after menopause, due to decreased estrogen levels [10,12].

Learning or education, especially in childhood, enhances brain structure and development by increasing brain vascularization, synapse number, and connections, which improve cognitive function [36,37]. Higher education levels are associated with lower cognitive decline as learning creates favorable structures and neurochemical alterations in the brain [36,37]. High socioeconomic status, high physical and social activities, and less dependency are protective factors for cognitive impairments [13,30-32]. People with high socioeconomic status generally have more social contact and activities that make them more active, less dependent, and perform higher physical activities leading to slower cognitive decline [13,30-32]. Moreover, these people can have good nutrition and can easily access the health services they need, maintaining their health in a good state that can delay cognitive declination [30-32].

On the contrary, elderly people living a solitary life and with failed marital status or unhealthy behaviors such as chronic smoking or alcohol consumption had a higher risk of developing cognitive impairments [10,13,15,22]. Elderly individuals who live alone and are widowed, divorced, or separated may have low social contact and activities that can initiate or exacerbate lower mood or depression, the high-risk factor for cognitive impairment [10,13-15]. Elderly people leading a lonely life may also harbor risky behaviors such as chronic alcohol drinking or smoking, as there is no family member to control them, which can increase cognitive impairment [10,13,15,22].” [Introduction, Line 63-102, Page 3-5]

Q-4: Justify the decision to stratify the HDS-R instead of treating it as a continuous variable.

A-4: Authors’ response: Thank you for your question. We treated HDS-R as continuous variable because of the following literature, which stating as follows: “The most common application of the HDS-R is its use as a screening test for dementia. Using the cut-off point of 20/21, we obtained the sensitivity of 0.90 and the specificity of 0.82 in our subject. Those optimum sensitivity and specificity were achieved by regarding a score of 20 or less as suggestive of dementia”. Reference: Imai Y, Hasegawa K. The revised Hasegawa’s Dementia Scale (HDS-R)- Evaluation of its usefulness as a screening test for dementia. J Hong Kong Coll Psychiatr. 1994;4:20-24. Available: https://easap.asia/index.php/find-issues/past-issue/item/503-v4n2-9402-p20-24.

Q-5: Cognitive function and impairment can differ across various domains such as working memory, executive function, psychomotor speed, etc. In a study to identify factors associated with cognitive impairment, the examination of specific cognitive domains should be essential. The omission of such an examination is a limitation of a study that purports to seek out risk factors for cognitive impairment.

A-5: Authors’ response: Thank you very much for your comments. As suggested, the examination of specific cognitive domains should be essential in a study to identify factors associated with cognitive impairment but this study was limited to do so. Therefore, this limitation was added and the previous paragraph of limitation “This study has a number of strengths and limitations. This is the first study to investigate the rate of impaired cognitive function using the Myanmar-translated version of HDS-R and its related comorbidities among Myanmar elderly. HDS-R has its own advantages. As it does not include questions assessing the reading and writing ability of respondents, it is convenient to use in illiterate people or in minor ethnic groups who cannot read and write the Myanmar language. Cognitive impairment could be checked easily by basic health staff using HDS-R. However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist. The study was conducted in one region in the central part of Myanmar, which limited the generalizability of the results, given that different socio-demographic features are represented across Myanmar. The causal relation between cognitive impairment and different risk factors could not be explored clearly owing to the cross-sectional design of the study.” was revised to read as follows: “This study has several strengths and limitations. This is the first study to investigate the prevalence of impaired cognitive function using the Myanmar-translated version of the HDS-R and its related comorbidities among Myanmar elderly. It was observed that 23.6% of males and 32.9% of females in this study had cognitive impairment detected by the HDS-R. The HDS-R has its own advantages. As it does not include questions assessing the reading and writing ability of respondents, it is convenient to use in illiterate people or in minor ethnic groups who cannot read and write the Myanmar language. Cognitive impairment could be checked easily by basic health staff using the HDS-R. However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist; therefore, cognitive impairment in specific domains such as executive function, spatial working memory, processing speed, attention, verbal memory, or verbal fluency could not be ruled out. The study was conducted in one region in the central part of Myanmar, which limited the generalizability of the results, given that different socio-demographic features are represented across Myanmar. The causal relationship between cognitive impairment and different risk factors could not be explored clearly owing to the cross-sectional design of the study.” [Discussion, Line 394-408, Page 21]

Q-6: Ethical considerations: please explain how you ensured that study participants with cognitive impairment were capable of providing informed consent.

A-6: Authors’ response: Authors’ response: Thank you for your question. If the patient is deemed incompetent to consent, consent based on legal proxies or advance directives were obtained. We revised the previous sentence from Methods section, “Research team members helped illiterate participants read the informed consent form. These participants were requested to mark their fingerprint if they understood the content of the informed consent form and agreed to participate in the study.” to read as follows: “Research team members helped illiterate participants read the informed consent form. These participants were requested to mark their fingerprint if they understood the content of the informed consent form and agreed to participate in the study. If participants were incompetent to consent, consent was taken from their legal proxies or advance directives.” [Methods, Line 200-204, Page 9]

Q-7: The findings are not novel or surprising, and the choice of variables was not anchored in any sort of theory. As such, the article seemed to be a fishing expedition to find statistically significant results. This is a problem because the wide confidence intervals in the regression analyses suggest the study was underpowered to detect certain effects.

A-7: Authors’ response: Thank you for your comment. I think you are pointing out the education variable confidence intervals in the regression analyses for UOR results “Illiterate (UOR = 14.2; 95% CI: 6.45–31.08) and AOR results “Illiterate (AOR = 9.1; 95% CI: 3.82–21.51)”. Following your suggestion, we categorized education variable to two categories (Middle school and above vs. Only read and write/primary school/illiterate) instead of three (Middle school and above, Only read and write/primary school, and Illiterate) and re-analyzed it. We found that the confidence intervals in the regression analyses becomes narrow: UOR results “Illiterate (UOR = 6.1; 95% CI: 2.91–12.75) and AOR results “Illiterate (AOR = 3.9; 95% CI: 1.77–8.42)”. The re-categorization of variable hasn’t effect the results of other variables. Other AOR results are remained the similar to our pervious analysis. Please refer below “Re-analysis Table 4”

Re-analysis Table 4 Multivariable logistic regression analysis of factors associated with cognitive impairment among Myanmar elderly (N=757)

Characteristics OR 95% CI AOR† 95% CI

Age

60-69

70-79 2.3 (1.63-3.33)*** 1.8 (1.19-2.70)**

≥80 4.9 (3.07-7.72)*** 3.9 (2.25-6.76)***

Gender

Male

Female 1.6 (1.12-2.25)** 1.1 (0.69-1.73)

Marital status

Single

Married 1.1 (0.53-2.31) 1.1 (0.48-2.46)

Separated/Divorced/Windowed 2.7 (1.30-5.61)** 1.4 (0.63-3.27)

Education

Middle school and above

Only read and write /Primary school 4.4 (2.07-9.24)*** 3.4 (1.56-7.52)**

Illiterate 14.2 (6.45-31.08)*** 9.1 (3.82-21.51)***

Dependent

No

Yes 2.5 (1.78-3.63)*** 1.6 (1.04-2.44)*

Family type

Living alone

Nuclear 0.3 (0.13-0.52)*** 0.4 (0.18-0.97)*

Extended 0.4 (0.25-0.76)** 0.5 (0.27-0.97)*

Three generation 0.4 (0.20-0.77)** 0.4 (0.21-0.94)*

Skip generation 0.4 (0.17-0.94)* 0.6 (0.22-1.45)

Alcohol, smoking and smokeless tobacco use

Non-user (Never use)

Ex-user 1.4 (1.01-1.95)* 1.3 (0.89-1.88)

Occasional user 1.6 (0.88-2.89) 1.6 (0.81-3.30)

Daily user 1.1 (0.27-4.02) 1.2 (0.25-5.47)

Self-rated health

Very poor/poor/fair

Good/very good 0.7 (0.53-1.03) 0.7 (0.44-0.99)*

Comorbidity

No. diseases

At least one disease 1.0 (0.65-1.49) 0.8 (0.49-1.34)

Two or more diseases 0.9 (0.61-1.45) 0.9 (0.50-1.57)

Low physical activities

No

Yes 0.9 (0.66-1.29) 1.3 (0.88-1.90)

Vision status

Good

Fair/poor 1.2 (0.85-1.58) 0.8 (0.58-1.21)

BMI §

Underweight

Normal 0.7 (0.45-0.95)* 0.9 (0.60-1.41)

Overweigh 0.8 (0.51-1.35) 1.4 (0.77-2.24)

Obese 0.4 (0.26-0.70)* 0.8 (0.44-1.40)

Hypertension

No

Yes 0.7 (0.54-1.02) 0.9 (0.58-1.29)

Diabetes mellitus

No

Yes 0.8 (0.55-1.21) 0.9 (0.57-1.41)

*p<0.05, **p<0.01, ***p<0.001; §BMI: Underweight (11.9-18.4), Normal (18.5-22.9), Overweigh (23.0-24.9), and Obese (≥25). † Adjusted for age, gender, marital status, education, dependent, family type, alcohol, smoking and smokeless tobacco use, self-rated health, no. of comorbidity, low physical activities, vision status, BMI, hypertension, and diabetes mellitus.”

However, our team are more interested to see how educational background of elderly effect the cognitive impairment especially among Myanmar elderly those who live in rural areas. Based on our findings, the policy makers can consider an appropriate intervention program for illiterate elderly population in rural areas those who are not getting much attention. More importantly, this study is the very first study reporting rate of cognitive impairments and its risks factors from Myanmar, a developing country with limited health resources. The previous studies also reported that low educational level in earlier life [16,17] was one of the important risk factors for cognitive decline among elderly. Regard to measurements, we carefully construct the survey questionnaire and chose variables based on literature review and reflecting the current situation rural elderly and applicable to the local community setting. To make it clear, we newly added independent variables categorization in the methods section as follow: “Independent variables

Socio-demographic characteristics, substance use behaviors, and health problems were considered as independent variables. The current age was categorized into three groups (60-69, 70-79, and ≥80) based on the 10-year age intervals. Marital status was categorized into three groups (single, married, and separated/divorced/windowed). Education was divided into three groups according to the educational background of respondents of the elderly: middle school and above, primary school, and only read and write, and illiterate. Family type was categorized into five groups: living alone, nuclear, extended, three generations, and skip generation to learn how family structures affect the cognitive functions of the elderly.

Substance use behaviors were grouped into the following categories: non-users (never use), ex-users, occasional users, and daily users to see the effect on the cognitive functions of respondents. Self-rated health, physical activities, and vision status were divided into two categories. The nutritional status of the elderly may play an important role in impairment of cognitive function. Therefore, Body mass index (BMI) was categorized as underweight, normal, overweight, and obese. Hypertension and diabetes mellitus were grouped into two categories according to self-reported and measurement results. The measurement cutoff point of blood pressure was 140/90 mmHg (hypertension: ≥140/90 mmHg) and random blood sugar was 200 mg/dL (diabetes mellitus: ≥ 200 mg/dL).” [Methods, Line 114-127, Page 7-8]

Q-8: Please report the manuscript in accordance with the STROBE guidelines for reporting observational research.

A-8: Authors’ response: Thank you for your comment. We reported the STROBE guideline for reporting observation research as follow:

STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies

Item no. Recommendation Page no. Line no.

Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract 1

2 1-3

26-50

(b) Provide in the abstract an informative and balanced summary of what was done and what was found 2 26-50

Introduction

Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 3-5 63-113

Objectives 3 State specific objectives, including any prespecified hypotheses 5-6 114-127

Methods

Study design 4 Present key elements of study design early in the paper 6 131

Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection 6-7 131-155

Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of participants 6 135-138

Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable 7-8 156-186

Data sources/ measurement 8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group 6

7

145-151

158-168

Bias 9 Describe any efforts to address potential sources of bias 21 394-408

Study size 10 Explain how the study size was arrived at 7 151-155

Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why 7-8 170- 168

Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 8 190-193

(b) Describe any methods used to examine subgroups and interactions - -

(c) Explain how missing data were addressed 7 153-155

(d) If applicable, describe analytical methods taking account of sampling strategy - -

(e) Describe any sensitivity analyses - -

Results

Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed 7 150-155

(b) Give reasons for non-participation at each stage 7 152-153

(c) Consider use of a flow diagram - -

Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders 9-12 209-239

Table 1 Table 2

Table 3

(b) Indicate number of participants with missing data for each variable of interest 7 153-155

Outcome data 15* Report numbers of outcome events or summary measures 12 233-239

Table 3

Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included 14-16 248-275

Table 4

(b) Report category boundaries when continuous variables were categorized 7 158-168

(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period - -

Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses

Discussion

Key results 18 Summarise key results with reference to study objectives 16 278-286

Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias 21 394-408

Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence 17-21 287-408

Generalisability 21 Discuss the generalisability (external validity) of the study results 21 404-406

Other information

Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based We included funding information in the editorial system.

Q-9: Abstract methods: you conducted a ‘multivariable’, not ‘multivariate’, logistic regression analysis.

A-9: Authors’ response: Thank you for your question. We corrected the error as you commented. To reflect the reviewer’s comment,, we revised the previous sentence from Abstract, “Descriptive statistics were prepared and multivariate logistic regression analysis performed.” to read as follows: “Descriptive statistics and multivariable logistic regression analyses were performed.” [Abstract, Line 34-35, Page 2]

Newly added references

22. Conti AA, McLean L, Tolomeo S, Steele JD, Baldacchino A. Chronic tobacco smoking and neuropsychological impairments: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2019; 96:143‐154. pmid:30502351

23. Evert, D.L., and Oscar-Berman, M. Alcohol-related cognitive impairments: An overview of how alcoholism may affect the workings of the brain. Alcohol Health Res World. 19(2):89-96, 1995.

24. Favieri F, Forte G, Casagrande M. The Executive Functions in Overweight and Obesity: a Systematic Review of Neuropsychological Cross-Sectional and Longitudinal Studies. Front Psychol. 2019; 10:2126. pmid: 31616340

25. Dye L, Boyle NB, Champ C, Lawton C. The relationship between obesity and cognitive health and decline. Proc Nutr Soc. 2017; 76(4):443‐454. pmid:28889822

26. Uhlmann RF, Larson EB, Koepsell TD, Rees TS, Duckert LG. Visual impairment and cognitive dysfunction in Alzheimer’s Disease. J Gen Intern Med. 1991;6(2):126-132. https://doi.org/10.1007/bf02598307.

29. Cuevas HE. Type 2 diabetes and cognitive dysfunction in minorities: a review of the literature. Ethn Health. 2019; 24(5):512‐526. pmid:28658961

34. Peters R. Ageing and the brain. Postgrad Med J. 2006; 82(964):84-8. pmid: 16461469

35. Forte G, De Pascalis V, Favieri F, Casagrande M. Effects of Blood Pressure on Cognitive Performance: a Systematic Review. J Clin Med. 2019; 9(1):34. pmid: 31877865

41. Saw YM, Than TM, Win EM, et al. Myanmar language version of the Revised Hasegawa’s Dementia Scale. Nagoya J Med Sci. 2018; 80(4):435-450. pmid:30587859

Additional revision

1. To reflect the reviewers’ comments, we revised the references by adding 9 new references and removing 6 old references. The total number of the references in the revised manuscript becomes 44. [References: Page 23-27]

2. We revised the abstract as follows: “Abstract

Background: Globally, elderly population with impaired cognitive function, such as dementia, has been accelerating, and Myanmar is no exception. However, cognitive function among elderly in Myanmar has rarely been assessed. This study aimed to identify the rate of cognitive impairment and its risk factors among the elderly in Myanmar.

Methods: This cross-sectional study was conducted at rural health centers in Nay Pyi Taw Union Territory, Myanmar, from December 2018 to January 2019. In total, 757 elderly individuals aged 60 years or over (males: 246 [32.5%], females: 511 [67.5%]) were interviewed using a face-to-face method with a pre-tested questionnaire Descriptive statistics and multivariable logistic regression analyses were performed.

Results: The rate of impaired cognitive function among participants was 29.9% (males: 23.6%; females: 32.9%). The following participants were more likely to present cognitive impairment: those aged 70–79 years (adjusted odds ratio [AOR] = 1.8; 95% confidence interval [CI]: 1.19–2.70) and 80 years or older (AOR = 3.9; 95% CI: 2.25–6.76); those who were illiterate (AOR = 9.1; 95% CI: 3.82–21.51); and those dependent on family members (AOR = 1.6; 95% CI: 1.04–2.44). The elderly livening with their families and those who reported having good health (AOR = 0.7; 95% CI: 0.44–0.99) were less likely to have cognitive impairment.

Conclusion: Using the HDS-R Myanmar version, this study reported that there out of five elderly participants had cognitive impairment, and its risk factors, altering policy makers that Myanmar needs to prepare for adequate healthcare services and social support for elderly with cognitive impairment. Future research should be performed not only to detect general cognitive impairment but also to differentiate specific cognitive domains impairments among Myanmar elderly. Longitudinal studies are needed to observe the causal and protective factors associated with cognitive impairments in Myanmar.” [Abstract, Line 27-50, Page 2]

3. In the fifth paragraph of the Results section describing for Table 4, three-generation family (UOR = 0.4; 95% CI: 0.17–0.94) was changed into skip-generation family (UOR = 0.4; 95% CI: 0.17–0.94). [Results, Line 257-258, Page 14]

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Gianluigi Forloni

22 Jun 2020

PONE-D-20-03550R1

Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

PLOS ONE

Dear Dr. Saw,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses all the points raised during the review process.

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Reviewers' comments:

Reviewer's Responses to Questions

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Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: (No Response)

Reviewer #2: Yes

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Reviewer #1: (No Response)

Reviewer #2: The manuscript is much improved from the first round, though the authors still need to address a few issues.

1. I am still unclear by what the authors mean when they write 'unable to subtract the value'. Please explain, in the manuscript, what you mean by 'value'. Are you referring to the ability to perform simple arithmetic?

2. The authors' response to my question about why they stratified the HDS-R should be added to the manuscript.

3. The chi-square critical values in Table 2 do not communicate useful information. Please report the exact p-values instead.

4. Since the study is cross-sectional, the authors cannot write about 'risk'. In the second paragraph of the discussion, they should replace 'risk' with 'odds'. The same edit should be made in other areas of the manuscript where the term risk may occur.

5. Please explain how missing data were handled in the regression analysis.

6. In the limitations section, the authors write that domain-specific cognitive impairment could not be assessed because a psychiatrist did not assess the participants. However, various cognitive tests exist to permit the assessment of specific cognitive domains, so the authors should say that the HDS-R allowed them to assess global cognitive impairment, and they were unable to measure impairment in specific domains.

7. I am uncertain of the value of figure 1 - suggest deletion.

8. many of the odds ratios in Table 4 are still fairly wide, despite the large sample size. The authors should add mention of this fact to the limitations.

9. At the end of the Ethical considerations section, the authors should mention that they reported their study in conjunction with the STROBE guidelines. Please cite the guidelines and include the STROBE checklist as an appendix.

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PLoS One. 2020 Jul 28;15(7):e0236656. doi: 10.1371/journal.pone.0236656.r004

Author response to Decision Letter 1


7 Jul 2020

Response letter (Response to Reviewers)

PONE-D-20-03550: Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

Thank you very much editor and reviewers for your valuable comments and suggestions. We have revised the manuscript accordingly. The revised and edited sentences (and words) are mentioned using a track-changes function in the revised manuscript. We also submitted a clean version of revised manuscript as a separate file. In below responses, we noted reviewer’s comments in black color and our responses in blue color.

Reviewer #1:

Reviewer #1: All comments have been addressed.

Authors’ response: Thank you very much for your insightful comments and suggestions on our manuscript, which has significantly improved by your constructive comments and suggestions.

Reviewer #2:

Reviewer #2: The manuscript is much improved from the first round, though the authors still need to address a few issues.

Authors’ response: Thank you very much for your careful reading of our manuscript and providing valuable comments and suggestions, which have been very helpful in improving our manuscript. We have revised our manuscript according to your comments and suggestions point by point.

Q-1. I am still unclear by what the authors mean when they write 'unable to subtract the value'. Please explain, in the manuscript, what you mean by 'value'. Are you referring to the ability to perform simple arithmetic?

A-1: Authors’ response: Thank you very much for your comments. Yes, we would like to mention the ability to perform simple arithmetic calculation. The participant needs perform serial subtractions of 7s. The question is "subtract 7 from 100". As suggested, we revised our previous sentences “Elderly individuals who lived in the study area less than six months, who were diagnosed with cognitive impairments along with mental and physical disorders (seriously ill), and who did not understand the Myanmar language and were unable to subtract the value were excluded from the study.” to read as follows: “Elderly individuals who lived in the study area less than six months, those who were diagnosed with cognitive impairments along with mental and physical disorders (seriously ill), those who did not understand the Myanmar language, and those who were unable to perform simple arithmetic calculation were excluded from the study.” [Methods, Line 135-139, Page 6]

Q-2. The authors' response to my question about why they stratified the HDS-R should be added to the manuscript.

A-2: Authors’ response: Thank you very much for your comments. As suggested, we added information of why we stratified the HDS-R in the manuscript as follows: “The dependent variable was cognitive impairment, which was dichotomous into “≤20 points” (presence of cognitive impairment) and “≥21 points” (absence of cognitive impairment). The cut-off point, 20/21, was applied based on the evaluation study of HDS-R test reporting 0.90 for sensitivity and 0.82 for specificity [42]. [Methods, Line 168-171, Page 7-8]

Q-3. The chi-square critical values in Table 2 do not communicate useful information. Please report the exact p-values instead.

A-3: Authors’ response: Thank you very much for your comments. We have reported exact p-values in the Table 1 and Table 2. [Results: Table 1, Page 10-11; Table 2, Page 12]

Q-4. Since the study is cross-sectional, the authors cannot write about 'risk'. In the second paragraph of the discussion, they should replace 'risk' with 'odds'. The same edit should be made in other areas of the manuscript where the term risk may occur.

A-4: Authors’ response: Thank you very much for your valuable comments. We have replaced 'risk' with 'odds' throughout the revised manuscript. [Discussion, Line 279, Page 17; Line 301, Page 18; Line 325, Page 19; Line 347, 358, Page 20; Line 363, Page 21]

Q-5. Please explain how missing data were handled in the regression analysis.

A-5: Authors’ response: Thank you very much for your comments. During data cleaning stage, we excluded 54 participants/cases those who missed to answer the dependent and independent variables. As suggested, we amended previous sentence “After cleaning the data and removing those with missing responses to the main outcome variables, 757 elderly participants (males: 246 [32.5%], females: 511 [67.5%]) were considered for the final data analysis.” to read as follows: “After cleaning the data and removing those with missing responses to the dependent and independent variables, 757 elderly participants (males: 246 [32.5%], females: 511 [67.5%]) were considered for the final data analysis.” [Methods, Line 154-157, Page 7]

Q-6. In the limitations section, the authors write that domain-specific cognitive impairment could not be assessed because a psychiatrist did not assess the participants. However, various cognitive tests exist to permit the assessment of specific cognitive domains, so the authors should say that the HDS-R allowed them to assess global cognitive impairment, and they were unable to measure impairment in specific domains.

A-6: Authors’ response: Thank you very much for your comments. As suggested, we revised the previous sentence from limitation section “However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist; therefore, cognitive impairment in specific domains such as executive function, spatial working memory, processing speed, attention, verbal memory, or verbal fluency could not be ruled out.” to read as follows: “However, cognitive impairment among the participants in this study was not confirmed by a psychiatrist. Therefore, cognitive impairment in specific domains such as executive function, spatial working memory, processing speed, attention, and verbal memory or verbal fluency could not be ruled out regardless of HDS-R allowance to assess cognitive impairment.” [Discussion-limitation, Line 393-397, Page 22]

Q-7. I am uncertain of the value of figure 1 - suggest deletion.

A-7: Authors’ response: Thank you very much for your comments. As suggested, we deleted figure 1.

Q-8. many of the odds ratios in Table 4 are still fairly wide, despite the large sample size. The authors should add mention of this fact to the limitations.

A-8: Authors’ response: Thank you very much for your valuable comments. As suggested, we have added below sentence to limitation “Furthermore, the fairly wide confidence intervals were observed for some predictors despite the large sample size.” [Discussion-limitation, Line 397-398, Page 22]

Q-9. At the end of the Ethical considerations section, the authors should mention that they reported their study in conjunction with the STROBE guidelines. Please cite the guidelines and include the STROBE checklist as an appendix.

A-9: Authors’ response: Thank you very much for your valuable suggestion. As suggested, at the end of the Ethical consideration section, we added STROBE checklist information as follows: “Furthermore, this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Appendix 1).” [Methods, Line 212-213, Page 9]

Newly added reference

1. Imai Y, Hasegawa K. The revised Hasegawa’s Dementia Scale (HDS-R)- Evaluation of its usefulness as a screening test for dementia. J Hong Kong Coll. Psychiatr .1994; 4:20-24.

Additional revision

1. We have corrected HSR-D to HDS-R in introduction section. [Introduction, Line 116-117, Page 5]

2. We amended the journal title abbreviations of reference no. 10,12,13, and 16.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Gianluigi Forloni

13 Jul 2020

Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

PONE-D-20-03550R2

Dear Dr. Saw,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Gianluigi Forloni

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Gianluigi Forloni

16 Jul 2020

PONE-D-20-03550R2

Cognitive impairment and its risk factors among Myanmar elderly using the Revised Hasegawa’s Dementia Scale: A cross-sectional study in Nay Pyi Taw, Myanmar

Dear Dr. Saw:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Gianluigi Forloni

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Appendix. STROBE (Strengthening the reporting of observational studies in Epidemiology) checklist.

    (PDF)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    Data are available upon request as a requirement of the Institutional Review Board, University of Public Health, Yangon, Myanmar for researchers who meet the criteria for access to confidential data. Researchers who would like to access to the data must contact Medical Care Division, Department of Medical Services, Office no. (47),Ministry of Health and Sports, Ottara Thiri Township, Ministry Zone, Nay Pyi Taw 15011, Myanmar. Tel: 95-673-411002, Fax: 95-673-411002. Email: medicalcare@mohs.gov.mm.


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