Effect of Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Plus Forest Bathing (FB) on Blood Pressure and Cognitive Health for Those Who Are Aged 50 and Above With Hypertension
Phase: NA
Conditions: High Blood Pressure
Sponsor: Hong Kong Metropolitan University

Document updated date: 20/04/2022 
Cover letter: 
 
Official project title:  
Efficacy of Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Plus Forest 
Bathing (FB) on blood pressure and cognitive health for those who are aged 50 and above with 
hypertension  
 
Funding source: N&HS Mini Grant 
 
Project ethical approval number: HE-NHS2021/02  
 
Document updated date: 20/04/2022 
 

Document updated date: 20/04/2022 
HONG KONG METROPOLITAN UNIVERSITY  
 
Study protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1: A flow diagram of the study 
 
 
An invitation poster will be displayed in the center or on the web page of the centers and 
Participants fitting the inclusion criteria will be selected by convenience sampling 
(T0) 
Arm 1: 
MIND diet (n= 16) 
Arm 2: 
MIND-FB (n= 16) 
3-month nutrition 
programme, 4 face-to-face 
nutrition counselling sessions  
(one session per week) 
3-month MIND-plus-FB 
programme,  
8 face-to-face sessions, 
nutrition and FB 
The outcome measurements will be collected immediately after the 4-week face-to-face 
intervention (T1), and thereafter at 12-week (T2)  
Eligible participants will be randomly assigned in a 1:1:1 ratio 
Arm 3: 
Control (n= 16) 
 
 
Usual care for 12 
weeks 
Participants will be recruited from local community elderly center 
e.g., PaK Tin Baptist Church Neighborhood Center 

Document updated date: 20/04/2022 
Work done by others 
Nonpharmacological interventions are effective in controlling BP with weight loss, the Dietary 
Approaches to Stop Hypertension diet (DASH), increase physical activity and a reduction in alcohol 
consumption (1;2).  
 
Dietary Intervention  
DASH diet is combination of high intake of whole-grain cereals, low-fat dairy products, fish, 
chicken and lean meats, with moderately high in protein and high in mineral and dietary fibre (3:4). 
The bioactive compounds of DASH are high in minerals (magnesium, potassium, calcium and 
phosphorus), vitamins (vitamin C and folate) and other phytochemicals including flavonoids and 
inorganic nitrate, which have antioxidant properties (4;5;6). The protective effects of DASH diet 
may be due to the multiple physiological mechanisms including anti-inflammatory effect (8), 
antioxidant capacity (9), generation of nitric oxide (10), sympathetic activation (11). Recent 
systematic review and meta-analysis of RCT (30 RCTs, n=5545 participants) showed that 
moderately strong evidence that DASH diet reduced both SBP and DBP [difference in means (MD): 
-3.2 mmHg and -2.5 mmHg] compared with a control diet (12). Adherence to DASH diet was 
inversely associated with odds of cardiovascular disease (RR, 0.80), diabetes (0.80) in prospective 
cohort studies; decrease systolic BP (MD, -5.2 mmHg) and diastolic BP (MD, -2.6 mmHg), HbA1c (-
0.53%) and body weight (-1.42 kg) in controlled trials (9). Mediterranean diet (MedDi) refers to 
high intake of olive oil, rich in green leafy vegetables and fruits, cereals, nuts, and legumes/pluses, 
moderate amount of fish and other meat, dairy products, red wine and low intake of eggs and 
sweets (10). Five potential metabolic and molecular mechanisms of high intake of flavonoids are 
lipid-lowering effect, protective against oxidative stress, inflammation and platelet aggregation, 
modification of hormones and growth factors involved in the pathogenesis of cancer, inhibition of 
nutrient sensing pathways by specific amino acid restriction and gut-microbiota-mediated 
production of metabolites influencing metabolic health (10;11;12).  
 
Two recent systematic reviews and meta-analyses showed that MedDi play a significant role in 
prevention of cardiovascular disease incidence (RR: 0.62), mortality (RR: 0.79) and stroke (RR: 0.73) 
(14;15). Although DASH and MedDi have shown plausible prospective evidence to support the 
benefits on cardiovascular health, it is necessary to be adapted to different geographic settings 
and cultural preferences and health conditions. The Mediterranean-DASH Intervention for 
Neurodegenerative Delay (MIND) diet (16;17) is a hybrid of the MedDi and DASH diet. Unlike DASH 
or MedDi, MIND diet emphasizes 10 brain-healthy foods including green leafy vegetables, other 
vegetables, berries, nuts, beans, whole grains, seafood, poultry, olive oil and wine) and 5 
unhealthy food groups (red meats, butter and stick margarine, cheese, pastries and sweets, and 
fried/fast food). Evidence from epidemiologic studies (1 cross-sectional and 5 longitudinal) 
observed that adherence to MIND dietary pattern is associated with better cognitive performance 
and lower risk of cognitive performance in older adults but inconsistently with cognitive decline 
(17). Several biological mechanisms of MIND may influence cognitive function (18;19). The blood 
brain barrier guards the brain from environmental insults that leads to oxidative stress and 
inflammation. Accumulation of amyloid-beta (Aβ) leads to neuritis plaques within neuron cells 
and finally induces brain atrophy. Limiting intake of butter, margarine, pastries and sweets, low 
consumption of saturated fats and trans-fat may result in improving the blood-brain barrier 
function and decreasing amyloid-beta (Aβ) aggregation (19). Long-chain n-3 fatty acids from fish 
may reduce Aβ formation and oxidative damage (20). The components of berries and green leafy 
vegetables are rich in flavonoids, folate and vitamin E and carotenoids and it have been shown to 
be antioxidant and anti-inflammatory effect in inhibition of formation of Aβ (21;22). These 
mechanisms directly impact brain health and may be indirectly via cardioprotective effects of the 

Document updated date: 20/04/2022 
related food components. Recent cross-sectional study found that MIND diet score is inversely 
associated with odds of reduced HDL cholesterol and general obesity (23). Comparing to DASH 
and MedDi, it does not include the consumption of fast foods, fried foods, butter, margarine and 
pastries and sweets. These foods are common in urban cities like HK. To our best knowledge, the 
cognitively protective or cardioprotective effects of the MIND diet has not been tested or 
compared in Asian. Cross-country variation in food supply, dietary behaviour and lifestyle are 
different from western and Asian, studies of the MIND are required in Asian and Chinese 
population.  
 
FB intervention  
Shinrin-Yoku, known as Forest Bathing (FB), it is a traditional Japanese practice of mindfully usage of 
five senses by immersing into nature. Recent review, 11 of 14 RCT and experimental studies 
measured blood pressure as the primary outcome. Six of the studies reported FB significant 
decreases in SBP (5.4 – 24.6%) and DBP (7 – 29.5%) among the participants after the intervention 
(24). Another meta-analysis included 20 trials with 732 participants shown that SBP and DBP of the 
forest environment was significantly lower (MD -3.15 mmHg and -1.75 mmHg) than that of the non-
forest environment (25). The possible therapeutic effects on FB including increasing in natural killer 
cells in cancer prevention, improvement in hypertension/coronary artery disease, improve allergies 
and respiratory conditions, improvement in mood disorders and stress and mental relaxation. The 
hypothesis mechanism is originally from concept of nature therapy, FB has a direct effect on 
increasing the parasympathetic nervous system by exposing to naturally occurring stimuli of five 
senses. Increasing the parasympathetic nervous system in turns to decreasing sympathetic nervous 
activity, cortisol levels and salivary amylase activity and leads to a stage of relaxation (24;25;26). 
These results indicated that FB is effective at reducing the blood pressure of participants, suggesting 
that they can potentially be used to manage hypertension. A feasibility study was conducted to 
measure and compare the psychological and physiological benefits of FB and DDBE among 
community middle-aged hypertensive adults. The intervention was conducted over four weeks to 
establish its feasibility and logistics, and the effects were measured pre-intervention (as the baseline) 
and immediately after completion of intervention at 4 weeks. The sustained effect of interventions 
was measured at eight weeks after the intervention. The findings of this feasibility study provided a 
preliminary evidence that, after 4-week intervention, FB was more effective than DDBE in lowering 
SBP of 7.45 mmHg (t=2.44; p<0.05) and the score of state anxiety level of 11.5 (t=5.12, p<0.001), 
trait anxiety levels of 6.4 (t=3.21, p<0.01), the total mood states of 14.8 (t=4.93, p<0.001), in the 
study population (30). Also, FB have been tested out in China and Taiwan and showed that FB 
enhanced heart rate and blood pressure functions. This relaxation strategy is suitable for middle-
aged and elderly individuals (27;28).  
 
MIND plus FB intervention  
MIND diet has been tested the enhancing cognitive function on western hypertensive population, 
but it has not been tested in Asian prehypertensive and hypertensive population. We hypothesis 
that MIND diet has effective of lower BP and maintain/enhance cognitive function on Chinese 
populations. FB is the additional effects of MIND in this proposed study. To the best of our 
knowledge, there is no study related to the effect of MIND plus FB in non-Chinese and Chinese 
studies. Thus, a pilot study to test out the effects of MIND and MIND plus FB is necessary.  
1. 
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Document updated date: 20/04/2022 
2. 
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https://doi.org/10.1093/advances/nmaa041 
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review. Nutrients, 7(11), 9139–9153. https://doi.org/10.3390/nu7115459 
11. Tosti, V., Bertozzi, B., & Fontana, L. (2018). Health Benefits of the Mediterranean Diet: Metabolic and 
Molecular Mechanisms. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 73(3), 
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12. Rosato et al. (2019). Mediterranean diet and cardiovascular disease: a systematic review and meta-analysis of 
observational studies. European Journal of Nutrition, 58(1), 173–191.  
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observational studies. European Journal of Nutrition, 58(1), 173–191.  
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review and meta-analysis of prospective cohort studies and randomized clinical trials. Critical Reviews in Food 
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15. Van Den Brink, et al. (2019). The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and 
Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less 

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Cognitive Decline and a Lower Risk of Alzheimer’s Disease-A Review. Advances in Nutrition, 10(6), 1040-
1065. https://doi.org/10.1093/advances/nmz054 
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https://doi.org/10.1016/j.jalz.2015.04.011 
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https://doi.org/10.1007/s12603-017-0909-0 
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an aged Alzheimer mouse model. Journal of Neuroscience, 25(12), 3032–3040.  
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in relation to cognitive decline. Annals of Neurology, 72(1), 135–143.  
23. Mohammadpour, S., Ghorbaninejad, P., Janbozorgi, N., & Shab-Bidar, S. (2020). Associations between 
adherence to MIND diet and metabolic syndrome and general and abdominal obesity: a cross-sectional study. 
Diabetology and Metabolic Syndrome, 12(1).  
24. Arjmand, G., Abbas-Zadeh, M., & Eftekhari, M. H. (2020). Effect of MIND diet intervention on cognitive 
performance and brain structure in healthy obese women: A randomized controlled trial. In bioRxiv. bioRxiv. 
https://doi.org/10.1101/2020.04.28.065813 
25. Ideno et al. (2017). Blood pressure-lowering effect of Shinrin-yoku (Forest bathing): A systematic review and 
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Cambridge, UK, 1989. 
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4.  Project plan and methodology: (max. 3 pages) 
 
Quantitative arm – Setting and Participants: A block randomization, single-blind design will be used. 
A three-arm RCT with equal allocation between the intervention and control groups (1:1:1) will be 
used; only the assessors will be blinded to the treatment assignment. Convenience sampling with 

Document updated date: 20/04/2022 
fitting the inclusion criteria will be selected as subjects.  Potential participants will be screened for 
blood pressure and health history at baseline assessment. The potential participants who meet the 
inclusion criteria will be asked to sign a consent form before participation in this study.  
 
Primary and secondary outcomes 
The primary outcomes will be systolic BP and the secondary outcomes will be point of care test 
(POCT) of lipid panel (HDL-cholesterol, triglycerides and LDL-cholesterol), cognitive function, waist-
to-hip ratio, body fat percentages and body mass index.  
 
Systolic BP will be determined by digital automatic device, Omron M6 Comfort (HEM-7221-E), for 
BP measurement (29). BP will be obtained in sitting position after enough rest (at least 10-15 min) 
and based on the mean of two measurements of participant. The POCT of lipid panel (HDL-
cholesterol, triglycerides and LDL-cholesterol) will be measured by the Food and Drug 
Administration (FDA) cleared and Centers for Disease Control and Prevention, Cholesterol Reference 
Method Laboratory Network (CRMLN) certified CardioChek PA (30). Body fat percentages and body 
mass index will be measured via bioelectrical impedance analysis (BIA) (31).  Cognitive function 
will be assessed via Hong Kong version of the Montreal Cognitive Assessment (HK-MoCA) (Cronbach 
alpha: 0.767; high sensitivity rate: 92.3% and good specific of 91.8%) for global cognition testing at 
baseline and each measurement. A cut-off score of 21/22 after adjustment of education level is 
recommended as indication for further evaluation of cognitive impairment and dementia (32). Waist 
circumference will be measured between the lower rib and iliac crest by tape meter. Waist to hip 
ratio will be calculated as waist circumference (cm) divided by hip circumference (cm) (33).  The 
outcome measurements will be recorded before the intervention (T0), immediately after the 4-week 
face-to-face intervention (T1) and 12 (T2) post-intervention to determine its short-term effects. 
 
Demographic and other covariates 
In addition to sociodemographic data (age, marital status, sex and education attainment), we will 
also collect data on physical activity, alcohol consumption, self-reported medical diagnosis, current 
use of medications, number of chronic diseases and cognitive levels.  
 
Diet scores 
Dietary intake will be assessed by using a validated 163-item semi-quantitative Harvard Food 
Frequency Questionnaire (FFQ) (50;51). There is no FFQ specifically for MIND diet. Morris’s group, 
the origin of MIND diet, is used Harvard FFQ to assess diet scores. Although it has not been used in 
Hong Kong Chinese population, the food list is user-friendly to Chinese culture with common food 
groups of green leafy vegetables, rice, fruits etc. Adherence to MIND dietary pattern will be assessed 
by calculating summation scores using predefined criteria (19:20). MIND score consists of 15 dietary 
components, namely 10 brain healthy food groups (green leafy vegetables, other vegetables, berries, 
nuts, beans, whole grains, seafood, poultry, olive oil and wine) and 5 unhealthy food groups (red 
meats, butter and stick margarine, cheese, pastries and sweets, and fried/fast food). A value of 0.0. 
0.5 or 1.0 has been assigned to each group. For high intake of brain healthy food group, participants 
will receive a score of 1 and the score is reversed for unhealthy food group. The total MIND diet 
score will be computed by summing all food groups, with a maximum score of 15 representing the 
highest adherence to the MIND diet.  
 
Inclusion and exclusion criteria 
A total of 48 those who are aged 50 and above and meet the inclusion criteria will be asked to 
sign a consent form before participation in this study. The inclusion criteria are (i) aged 50 and 
above; (ii) Chinese ethnicity; (iii) ability to speak and understand Chinese; (iv)fulfilment of the AHA 

Document updated date: 20/04/2022 
criteria for stage 1 and stage 2 hypertension; and (v) physical fitness to take part in mild-intensity 
exercises e.g. slow walking, standing light work etc. The exclusion criteria are (i) poorly controlled 
chronic disease, including chronic obstructive pulmonary disease, cardiovascular disease, kidney 
disease and diabetes, (ii) have allergy to more than one type of food (nuts, berries, olive oil, or 
fish), (iii) Use of medications to treat Alzheimer’s disease or Parkinson’s disease, (iv) pregnant, (v) 
participation in any dietary or relaxation programme within the past 3 months, (vi) experienced 
chronic pain and muscle weakness, and (vii) were unable to walk independently were excluded. 
All screening tests will be carried out by a trained research assistant. Based on AHA criteria, stage 
1 hypertension is suggested to be defined as SBP 130-130 mmHg or DBP 80-89 mmHg, and stage 
2 is suggested to be defined as SBP ≥140 mmHg or DBP ≥ 90 mmHg. 
 
Interventions 
MIND diet group 
The MIND diet intervention used for this study is based on the MIND diet developed by Morris 
and colleagues in 2015 (16;17). We adapted Arjmand group’s 3-month MIND diet intervention (24). 
MIND diet intervention will be a 3-month nutrition programme consisting of 4 face-to-face 
nutrition counselling sessions (one session per week, 60 min per session) in the activity room of 
each participating community centre. All intervention sessions will be conducted by a registered 
nutritionist and trained student helpers. In the nutrition sessions, the participants will learn to 
modify their diet to meet MIND diet guidelines. MIND diet promotes 10 healthy foods and limits 
5 unhealthy food groups. A 7-day sample menu is developed, meeting the required number of 
servings per day every week, as reference. Each intervention session will be conducted by a 
nutritionist with the help of a research assistant. To maintain consistency, one nutritionist, with 
one research assistant (with a degree in nursing or nutrition), will deliver all the interventions. 
Topics covered during the programme including how to promote behaviour change strategies; 
overview of MIND diet; discussion of establishing rapport with participants and instruction 
regarding dietary adoption and adherence checks using logbook to enable informed decision 
making and adherence to nutritional recommendations.  
 
MIND-plus-FB intervention 
The MIND-plus-FB intervention will last 4 weeks, consisting of 8 sessions (two sessions per week). 
The MIND diet will follow the steps mentioned in the previous section. MIND diet intervention 
will be one session per week, 60 min per session, in the activity room of each participating 
community centre. FB will be another session per week, 2 hours forest bathing sessions on 4-
consecutive weekends in a country park at daytime with sunny, cloudy or drizzling conditions. The 
walking distance for each forest bathing is one to two kilometres. The session will be rescheduled 
to the next weekend if there is heavy rainy day. The best temperatures for forest bathing session 
are ranging from 11 to 25 °C. In view of humidity and temperatures in HK, FB is suitable to be 
conducted between January to June, and September to December respectively. On the day of FB, 
participants will gather at the entrance of the country park for briefing and measuring physical 
parameters e.g., BP and pluses.  
 
FB coach will begin the FB intervention by a set of experiential thresholds, called Standard 
Sequence (25;26) to facilitate participants’ deeper connection to the nature via sensory activity 
along the path. Each intervention session will follow an identical invitation: (i) sharing experience 
for the forest (20 minutes) (ii) center yourself at the pleasure of moment using five senses (20 
minutes), (iii) wander down the designed forest path to slow down both physically and mentally 
(20 minutes) and (iv) build up a deeper connection to forest by alertness what happen of the 
surrounding (20 minutes). Participants will be given around 20 minutes of rest and sharing time 

Document updated date: 20/04/2022 
between each activity change. The tea Ceremony, as second threshold, is incorporated at the end of 
each session. All intervention sessions will be conducted by a certified FB coach with wilderness 
first aid certificate by the Association of Nature & Forest therapy (ANFT). The FB coach will 
ensure safety during FB. The coach-to-participant ratio is approximately 1:16. Participants will 
then be required to self-practice 2h FB in the country park at daytime at the weekends of 8th week 
and 12th week of the intervention. 
 
Control group 
A control group with routine care will be added to illuminate the effect of MIND and MIND-plus-
FB.  
 
29. Topouchian et al. (2014). Validation of four devices: Omron M6 Comfort, Omron HEM-7420, Withings BP-
800, and Polygreen KP-7670 for home blood pressure measurement according to the European society of 
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Handheld Point of Care Testing Devices : Elemark TM and Cardiochek PA Results. Annals of Clinical and 
Laboratory Research, 7(1), 290.  
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weight loss in overweight and obese women. British Journal of Nutrition, 99(2), 432–441. 
https://doi.org/10.1017/S0007114507815789 
32. Yeung et al. (2014). A validation study of the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) 
in Chinese older adults in Hong Kong. Hong Kong Medical Journal, 20, 504-510.  
33. Department of Health. (2016). Non-Communicable Diseases Watch March 2016 – Keep a Healthy Waistline. 
https://www.chp.gov.hk/files/pdf/ncd_watch_mar2016.pdf 
34. Rimm et al. (1992). Reproducibility and validity of an expanded self-administered semiquantitative food 
frequency questionnaire among male health professionals. American Journal of Epidemiology, 135(10), 1114–
1126.  
35. Feskanich et al. (1993). Reproducibility and validity of food intake mesurements from a semiquantitative food 
frequency questionnaire. Journal of the American Dietetic Association, 93(7), 790–796. 
https://doi.org/10.1016/0002-8223(93)91754-E 
 
Sample size 
There is no previous RCT on the MIND diet intervention. We first calculate the effect size (f=0.43) 
by using results from the DASH trial using systolic BP as a primary outcome variable (50); we 
consider the type I error of 5% (α = 0.05), type II error of 20% (β = 0.2, power = 80%). A total of 48 
participants will be required (i.e., 16 per group) for this pilot study. The sample size calculation 
was based on the F test using G*Power 3.1.9.4.