Dementia is a rapidly growing global public health problem. Worldwide, around 50 million people have dementia, with approximately 60% living in low-and middle-income countries (LMIC). Every year, there are nearly 10 million new cases. The total number of people with dementia is projected to reach 82 million in 2030 and 152 million in 2050. Dementia leads to increased costs for governments, communities, families and individuals, and to loss in productivity for economies. In 2015, the total global societal cost of dementia was estimated to be US$ 818 billion, equivalent to 1.1% of global gross domestic product (GDP).
Crucially, while age is the strongest known risk factor for cognitive decline, dementia is not a natural or inevitable consequence of ageing. Several recent studies have shown a relationship between the development of cognitive impairment and dementia with lifestylerelated risk factors, such as physical inactivity, tobacco use, unhealthy diets and harmful use of alcohol.
Certain medical conditions are associated with an increased risk of developing dementia, including hypertension, diabetes, hypercholesterolemia, obesity and depression. Other potentially modifiable risk factors include social isolation and cognitive inactivity.
The existence of potentially modifiable risk factors means that prevention of dementia is possible through a public health approach, including the implementation of key interventions that delay or slow cognitive decline or dementia.
In May 2017, the Seventieth World Health Assembly endorsed the Global action plan on the public health response to dementia -2025(WHO, 2017a

# GUIDELINE DEVELOPMENT METHODS
The process of development of these guidelines followed the WHO handbook for guideline development and involved:
- recruitment of the guideline development group (GDG);
- declaration of interest by GDG members and peer reviewers;
- scoping review to formulate questions and select outcomes;
- identification, appraisal and synthesis of available evidence;
- formulation of recommendations with inputs from a wide range of stakeholders; and 6. preparation of documents and plans for dissemination.
The GDG, an international group of experts, provided input into the scope of the guidelines and assisted the steering group in developing the key questions. A total of 12 PICO (population, intervention, comparison and outcome) questions were developed.
To address the PICO questions, a series of searches for systematic reviews was conducted and Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profiles prepared.
During a meeting at WHO headquarters in Geneva, 2-3 July 2018, the GDG discussed the evidence, sought clarifications and interpreted the findings in order to develop recommendations. The GDG considered the balance of benefit and harm of each intervention; values and preferences; costs and resource use; and other relevant practical issues for providers in LMIC.
When making a strong recommendation, the GDG was confident that the desirable effects of the intervention outweigh any undesirable effects. When the GDG was uncertain about the balance between the desirable and undesirable effects, the GDG issued a conditional recommendation. Strong recommendations imply that most individuals would want the intervention and should receive it, while conditional recommendations imply that different choices may be appropriate for individual patients and they may require assistance at arriving at management decisions.
The GDG members reached a unanimous agreement on all the recommendations and ratings.
xii Risk reduction of cognitive decline and dementia: WHO guidelines

# SUMMARY OF RECOMMENDATIONS

# Physical activity interventions
Physical activity should be recommended to adults with normal cognition to reduce the risk of cognitive decline.

# Quality of evidence: moderate

# Strength of the recommendation: strong
Physical activity may be recommended to adults with mild cognitive impairment to reduce the risk of cognitive decline.

# Quality of evidence: low

# Strength of the recommendation: conditional

# Tobacco cessation interventions
Interventions for tobacco cessation should be offered to adults who use tobacco since they may reduce the risk of cognitive decline and dementia in addition to other health benefits.

# Quality of evidence: low
Strength of the recommendation: strong

# Nutritional interventions
The Mediterranean-like diet may be recommended to adults with normal cognition and mild cognitive impairment to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: moderate

# Strength of the recommendation: conditional
A healthy, balanced diet should be recommended to all adults based on WHO recommendations on healthy diet.

# Quality of evidence: low to high (for different dietary components)
Strength of the recommendation: strong Vitamins B and E, polyunsaturated fatty acids and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: moderate
Strength of the recommendation: strong

# Interventions for alcohol use disorders
Interventions aimed at reducing or ceasing hazardous and harmful drinking should be offered to adults with normal cognition and mild cognitive impairment to reduce the risk of cognitive decline and/or dementia in addition to other health benefits.

# Quality of evidence: moderate (for observational evidence)
Strength of the recommendation: conditional

# Cognitive interventions
Cognitive training may be offered to older adults with normal cognition and with mild cognitive impairment to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: very low to low

# Strength of the recommendation: conditional

# Social activity
There is insufficient evidence for social activity and reduction of risk of cognitive decline/dementia. Social participation and social support are strongly connected to good health and wellbeing throughout life and social inclusion should be supported over the life-course.
xiii Executive Summary

# Weight management
Interventions for mid-life overweight and/or obesity may be offered to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: low to moderate
Strength of the recommendation: conditional

# Management of hypertension
Management of hypertension should be offered to adults with hypertension according to existing WHO guidelines.

# Quality of evidence: low to high (for different interventions)
Strength of the recommendation: strong Management of hypertension may be offered to adults with hypertension to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: very low (in relation to dementia outcomes)
Strength of the recommendation: conditional

# Management of diabetes mellitus
The management of diabetes in the form of medications and/or lifestyle interventions should be offered to adults with diabetes according to existing WHO guidelines.

# Quality of evidence: very low to moderate (for different interventions)

# Strength of the recommendation: strong
The management of diabetes may be offered to adults with diabetes to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: very low

# Strength of the recommendation: conditional

# Management of dyslipidaemia
Management of dyslipidaemia at mid-life may be offered to reduce the risk of cognitive decline and dementia.

# Quality of evidence: low

# Strength of the recommendation: conditional

# Management of depression
There is currently insufficient evidence to recommend the use of antidepressant medicines for reducing the risk of cognitive decline and/or dementia.
The management of depression in the form of antidepressants and/or psychological interventions should be provided to adults with depression according to existing WHO mhGAP guidelines.

# Management of hearing loss
There is insufficient evidence to recommend use of hearing aids to reduce the risk of cognitive decline and/or dementia.
Screening followed by provision of hearing aids should be offered to older people for timely identification and management of hearing loss as recommended in the WHO ICOPE guidelines.

# BACKGROUND AND RATIONALE FOR THESE GUIDELINES
Dementia, a group of disorders characterized by a decline from a previously attained cognitive level that affects activities of daily living (ADL) and social functioning, poses one of the greatest global challenges for health and social care in the 21st century.
In 2015, dementia affected 50 million people worldwide (or roughly 5% of the world's elderly population, i.e. those above the age of 60 years).
The number of people with dementia is expected to increase to 82 million in 2030 and 152 million by 2050 with the estimated proportion of the population aged 60 and over with dementia at a given time between 5 to 8% 1 because dementia rises exponentially during old age and the world's population is ageing. These projections assume constant age-and sex-specific prevalence of dementia over time, and, accordingly, the steepest rises are expected especially in low-and middleincome countries (LMIC), where the demographic changes will be more marked.
Dementia is a major cause of disability and dependency among older people worldwide, and it has a significant impact not only on individuals but also on carers, families, communities and societies.
Dementia accounts for 11.9% of the years lived with disability due to a noncommunicable disease (NCD) worldwide. Dementia leads to increased costs for governments, communities, families and individuals, and to loss in productivity for economies. The annual global cost of dementia is estimated to be US$ 818 billion (OECD, 2015;WHO, 2017b). Nearly 85% of costs are related to family and social, rather than medical, care (GBD 2015Neurological Disorders Collaborator Group, 2017. Most health systems are ill-equipped and under-resourced to respond to the current needs associated with dementia. Thus, societal ageing and the associated increases in dementia prevalence will likely have major health-service implications for the care of people with dementia and support for affected families.
There are many different causes and types of dementia. Primary dementias include: dementia due to Alzheimer disease (AD), vascular dementia, dementia with Lewy bodies and frontotemporal dementia (in which the decline in cognitive abilities itself is mostly due to an underlying neurodegenera-tive process and not directly caused by other etiologies). Alzheimer disease is the most common, followed by vascular dementia and dementia with Lewy bodies. Mixed dementia with features of more than one type is also common, especially in older adults, while frontotemporal dementia is a less common form but relatively more frequent before old age.
Secondary dementias are those caused by, or closely related to, some other recognizable disease, such as HIV, head injury, multiple sclerosis, thyroid disorders or vitamin B12 deficiency. In these secondary dementias, cognitive impairment is typically accompanied by symptoms and signs in other organ systems and the treatment focuses on management of the underlying disease.
For the scope of these guidelines we refer to primary dementias. Though early treatment of some diseases may have the potential to prevent the onset of secondary dementias, we are not including these secondary dementias in the scope of these guidelines since there are prevention or appropriate management and treatment strategies for most of these specific diseases and conditions, which effectively reduce dementia-related signs and symptoms. However, late-onset dementia is a heterogeneous and multifactorial condition and some factors (i.e. head trauma, B12 deficiency earlier in life) may also contribute to the development of dementia later in life (not only secondary dementia).

# RISK FAC TOR S FOR DEMENTIA
Non-modifiable risk factors for dementia include gene polymorphisms, age, gender, race/ethnicity and family history. Crucially, while age is the strongest known risk factor for cognitive decline, dementia is not a natural or inevitable consequence of ageing.  (Kane et al., 2017); the World Alzheimer report 2014 (Prince, et al., 2014) and the report by the Lancet Commission on Dementia Prevention, Intervention, and Care (Livingston et al., 2017). The current focus on modifiable risk factors is justified by their potential to be targeted for prevention of dementia, and/or the delay of the progression of cognitive decline.

# NEED FOR THESE GUIDELINES
The existence of potentially modifiable risk factors means that prevention of dementia is possible through a public health approach, including the implementation of key interventions that delay or slow cognitive decline or dementia.

# RELATED WHO GUIDELINES AND TOOLS
Several existing WHO guidelines and tools designed for the general population are relevant for addressing health conditions that may increase the risk of cognitive decline or dementia in individuals with normal cognition or mild cognitive impairment (MCI).
The following WHO guidelines and tools were consulted when developing the current guidelines:
- mhGAP Intervention guide -Version 2.0 for mental,

# TARGET AUDIENCE
The guidelines are primarily targeted at health care providers working at a first or second level facility or at district level, including basic outpatient and inpatient services. The health care providers could be doctors, nurses or other cadres of health workers.
Quality improvement teams at all levels of the system will benefit from the work.
In addition, the guidelines and their derivative products have implications for policy-makers, health care planners and programme managers at national and international level, as well as the general population.

# GOALS AND OBJECTIVES
- To provide evidence-based recommendations on lifestyle behaviours and interventions to delay or prevent cognitive decline and dementia in the general population.
- To provide evidence-based recommendations on management of specific physical and mental health conditions to delay or prevent cognitive decline and dementia.  9 the Global strategy to reduce harmful use of alcohol, 10 and the Global strategy on diet, physical activity and health. 11

# GUIDING PRINCIPLES
The following principles have informed the development of these guidelines and should guide their implementation:
- The guidelines should expedite the achievement of the goals outlined in the Global action plan on the public health response to dementia 2017-2025, as well as target 3.4 of the Sustainable Development Goals, which focuses on reducing the premature mortality from NCDs and the promotion of mental health and well-being (UN, 2019).
- The process of developing these guidelines, and their subsequent implementation, should concretely foster the right to equal levels of health for people at risk of cognitive decline and dementia and promote their active involvement.
- The recommendations should be implemented with accompanying efforts to safeguard the human rights of persons living with cognitive decline and dementia, including reduction of stigma and discrimination, reducing barriers to seek health and social care services, and ensuring informed decision-making in treatment choices.
Implementation of the recommendations should be tailored to the local context, including the availability of financial and human resources. However, the inequities addressed in these guidelines are common across all countries, and should be made a priority in health services.

# GUIDELINE DEVELOPMENT PROCESS 2
The process of developing these guidelines followed the WHO Handbook for guideline development (2nd edition, / medicinedocs/en/m/abstract/Js22083en/).
It consisted of the following steps.

# GUIDELINE DEVELOPMENT GROUP

# DECLARATIONS OF INTEREST BY THE GDG MEMBERS AND EXTERNAL REVIEWERS
All GDG members, peer reviewers and systematic review team members were requested to complete the DoI prior to the evidence review process for guideline development. Invitations to participate in the GDG meeting were sent only after the DoI had been reviewed and approved. The GDG members were also required to complete a confidentiality undertaking. Once received, the WHO Secretariat reviewed the DoIs, as well as additional information (internet and bibliographic database search), and evaluated if there were any conflicts of interest and if so, whether these required a management plan. The group composition was finalized after this process.
The names and brief biographies of the members being considered for participation in the GDG were disclosed for public notice and comment prior to the meeting.
At the beginning of the GDG meeting, the DoI of each GDG member were presented and GDG members, as well as external partners, were asked to update their DoI with relevant changes by notifying the WHO Secretariat.
Declarations of interest were reassessed for potential conflict before the face-to-face meeting in Geneva.
None of the members had major conflicts of interest.
All decisions were documented (see Annex 2).

# COLLABORATION WITH EXTERNAL PARTNERS

# IDENTIFYING, APPRAISING AND SYNTHESIZING AVAILABLE EVIDENCE
The procedure of the scoping review to identify the draft population, intervention, comparison, The GDG provided input into the scope of the guidelines and assisted the steering group in developing the key questions. Twelve PICO-structured questions were developed (Annex 3).
Outcomes were rated by GDG members according to their importance, as "critical", "important" or "unimportant". Those outcomes rated as critical and important were selected for inclusion into the PICO.
Regular communication and discussions with the GDG were held by email and teleconferences, respectively.
The systematic review team developed protocols to review the evidence that existed for the interventions to reduce the risk of cognitive decline and/ or dementia (as outlined in the PICO questions) for adults with normal cognition or MCI (Annex 4).
Existing relevant systematic reviews were identified for each of the PICO questions. The steering group assessed the quality of existing reviews using the assessment of multiple systematic reviews (AMSTAR) checklist. Systematic reviews found to be of high quality were also assessed for timeliness to ensure that the most current evidence was used.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (Guyatt et al., 2011)

# DECISION-MAKING DURING THE GDG MEETING
The GDG met at the WHO headquarters in Geneva,

# DOCUMENT PREPARATION AND PEER REVIEW
The draft guideline and evidence profiles prepared by WHO staff and the GDG were circulated to the ERG and the steering group. The role of the ERG was to identify any errors or missing data and to comment on clarity, setting-specific issues and implications for implementation rather than changing the recommendations. All inputs and remarks were discussed and agreed with the GDG by email.
This section provides an overview of each PICO question described under the following headings: background; recommendations and additional considerations; supporting evidence for the recommendations and the rationale for the recommendations based on the evidence synthesized as well as criteria listed in the EtD tables. Complete evidence profiles for each PICO question including the GRADE tables and the EtD tables are included in the Web Annex.

# EVIDENCE AND RECOMMENDATIONS

# PHYSICAL ACTIVITY INTERVENTIONS BACKGROUND
A physically active lifestyle is linked to brain health.
In large observational studies with follow-up periods extending decades, physically active people seem less likely to develop cognitive decline, all-cause dementia, vascular dementia and Alzheimer disease when compared with inactive people (Gallaway et al., 2017;Hamer & Chida, 2009;Sofi et al., 2011;Stephen et al., 2017). Especially, the highest levels of physical exercise seem to be most protective (Hamer & Chida, 2009;Sofi et al., 2011). Physical activity seems to have beneficial effects on brain structures, which may underlie this association (Rovio et al., 2010

# RECOMMENDATIONS AND CONSIDERATIONS RECOMMENDATION 1:
Physical activity should be recommended to adults with normal cognition to reduce the risk of cognitive decline. Below is an extract from these recommendations for adults 65 years and above:
For adults 65 years and above, physical activity includes recreational or leisure-time physical activity, transportation (e.g. walking or cycling), occupational (if the person is still engaged in work), household chores, play, games, sports or planned exercise, in the context of daily, family, and community activities. In order to improve cardiorespiratory and muscular fitness, bone and functional health, and reduce the risk of NCDs, depression and cognitive decline, the following are recommended:
- Adults aged 65 years and above should do at least 150 minutes of moderate-intensity aerobic physical activity throughout the week, or do at least 75 minutes of vigorous-intensity aerobic physical activity throughout the week, or an equivalent combination of moderateand vigorous-intensity activity.
- Aerobic activity should be performed in bouts of at least 10 minutes' duration.
For additional health benefits, adults aged 65 years and above should increase their moderateintensity aerobic physical activity to 300 minutes per week, or engage in 150 minutes of vigorous-intensity aerobic physical activity per week, or an equivalent combination of moderateand vigorous-intensity activity.
- Adults of this age group with poor mobility should perform physical activity to enhance balance and prevent falls on 3 or more days per week.
Muscle-strengthening activities should be done involving major muscle groups, on 2 or more days per week.
- When adults of this age group cannot do the recommended amounts of physical activity due to health conditions, they should be as physically active as their abilities and conditions allow.
Overall, across all the age groups, the benefits of implementing the above recommendations, and of being physically active, outweigh the harms. At the recommended level of 150 minutes per week of moderate-intensity activity, musculoskeletal injury rates appear to be uncommon. In a populationbased approach, in order to decrease the risks of musculoskeletal injuries, it would be appropriate to encourage a moderate start with gradual progress to higher levels of physical activity.

# Additional considerations include:
- Physical activity is easily available for everybody and has a large range of beneficial effects.
- Aerobic activity plays a key role in the beneficial effect of physical activity.

# SUPPORTING EVIDENCE AND RATIONALE
For physical activity interventions (e.g. aerobic,
resistance training or multicomponent physical activity) compared with usual care or no intervention, four systematic reviews were identified for six different physical activity interventions (Barha et al., 2017;Barreto et al., 2017;Northey et al., 2018;Song et al., 2018). These were:
- Aerobic exercise intervention versus usual care or no intervention in adults with normal cognition.

# Training exercise intervention versus usual care or
no intervention in adults with normal cognition.

# Multimodal exercise intervention versus usual
care or no intervention in adults with normal cognition.

# Aerobic exercise intervention versus usual care or
no intervention in adults with MCI.

# Training exercise intervention versus usual care or
no intervention in adults with MCI.

# Multimodal exercise intervention versus usual
care or no intervention in adults with MCI.

# TOBACCO CESSATION INTERVENTIONS
Tobacco dependence is the leading cause of preventable death globally, causing an estimated 5 million deaths per year (WHO, 2011) and worldwide medical costs ranging in billions of US dollars (Lightwood et al., 2000). Tobacco is the major risk factor for a number of conditions, including many types of cancers, cardiovascular diseases (CVDs) and risk factors, and respiratory disorders (US Department of Health Human Services, 2004), and tobacco cessation has been demonstrated to significantly reduce these health risks (Pirie et al., 2013). Tobacco cessation has also been associated with reduced depression, anxiety and stress, and improved mood and quality of life compared with continuing to smoke (Taylor et al., 2014).
Tobacco dependence is also associated with other disorders and age-related conditions, such as frailty and work ability in older people (Amorim et al., 2014;Kojima et al., 2015), as well as dementia and cognitive decline (Durazzo et al., 2014).
Interventions to treat tobacco dependence can be very diverse, based on either or both behavioural/ psychological strategies and various pharmacological treatments. Non-pharmacological interventions can have mixed results (Niaura, 2008). Counselling is the most frequently used approach, but others have also

# SUPPORTING EVIDENCE AND RATIONALE
No systematic reviews comparing tobacco cessation interventions with no intervention were identified.
A large body of observational evidence is available on tobacco smoking as a risk factor for cognitive impairment and dementia. These studies show an association between tobacco smoking (including in mid-life) and dementia, or cognitive decline, in later life (Beydoun et al., 2014;Di Marco et al., 2014;Lafortune et al., 2016;North et al., 2015;Xu et al., 2015;Zhong et al., 2015). Only limited adverse events have been reported and only for pharmacological interventions (Motooka et al., 2018). Therefore, any type of intervention aimed at tobacco cessation is likely to be more beneficial than detrimental.
The GDG made a strong recommendation although evidence from experimental intervention trials is not available, since tobacco use has substantial established harm and the epidemiological/ observational evidence on tobacco use and increased risk of dementia fulfils most of the Bradford-Hill's criteria for causation (Lafortune et al., 2016). The evidence is strong, the population attributable risk is high, reproducible in different settings and with different study designs, specific, and indicates a doseresponse effect. In addition, criteria such as temporality (mid-life smoking is correlated to a higher risk of late life dementia) (Lafortune et al., 2016), coherence (experimental laboratory results are in keeping with the observational evidence) (Durazzo et al., 2014) and mechanistic evidence suggest that smoking causes brain damage, underpinning subsequent cognitive decline.

# RECOMMENDATIONS AND CONSIDERATIONS
Interventions for tobacco cessation should be offered to adults who use tobacco since they may reduce the risk of cognitive decline and dementia in addition to other health benefits.

# Quality of evidence: low
Strength of recommendation: strong

# NUTRITIONAL INTERVENTIONS
Adults with normal cognition or MCI
Dietary supplements (e.g. B vitamins, antioxidants, omega-3 and ginkgo)
Care as usual/placebo or one treatment versus another
Healthy dietary pattern (e.g. the Mediterranean diet)
Care as usual or no intervention
-  (Swaminathan & Jicha, 2014). Therefore, dietary factors may be involved in the development of dementia, both directly and through their role on other risk factors, and a healthy diet may have a great preventive potential for cognitive impairment.
The Mediterranean diet is the most extensively studied dietary approach, in general as well as in relation to cognitive function. Several systematic reviews of observational studies have concluded that high adherence to the Mediterranean diet is associated with decreased risk of MCI and AD, but modest adherence is not (Singh et al., 2014;. Moreover, among participants with normal cognition, higher adherence is associated with better episodic memory and global cognition (Loughrey et al., 2017). Other promising dietary approaches associated with better cognitive function include: dietary approaches to stop hypertension (DASH) (Berendsen et al., 2017;Morris et al., 2015a;2015b;Wengreen et al., 2013); and the brain health-specific Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet.
Concerning individual foods and nutrients, consumption of fruit and vegetables (Jiang et al., 2017; and fish (Bakre et al., 2018;Zhang et al., 2016) are most consistently associated with decreased risk of dementia.
Higher fish consumption has been linked to lower memory decline among healthy participants in many studies (Samieri et al., 2018), as well as intake of polyunsaturated fatty acids (PUFA) (fish-derived) (Zhang et al., 2016). Other foods and nutrients that have been associated with reduced risk of dementia or cognitive impairment are nuts, olive oil and coffee (Solfrizzi et al., 2017). Evidence has also been reported concerning folate, vitamin E, carotenes, vitamin C and vitamin D (Balion et al., 2012;Dangour et al., 2010;Rafnsson et al., 2013;Travica et al., 2017), but findings are inconsistent.

# RECOMMENDATIONS AND CONSIDERATIONS RECOMMENDATION 1:
The Mediterranean-like diet may be recommended to adults with normal cognition and MCI to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: moderate Strength of the recommendation: conditional

# RECOMMENDATION 2:
Healthy, balanced diet should be recommended to all adults based on WHO recommendations on healthy diet.

# Quality of evidence: low to high (for different dietary components) Strength of the recommendation: strong

# RECOMMENDATION 3:
Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: moderate Strength of the recommendation: strong
Additional considerations include:
- The evidence and recommendations provided assume that the nutritional status and potential micronutrients deficiencies in both mid-life and old age have been assessed and treated.
- A balanced and varied diet represents a natural source of polyphenols and protein.
- The recommendation about vitamins B and E, PUFA and multi-complex supplementation applies to people without nutrient deficiency.

# SUPPORTING EVIDENCE AND RATIONALE
Observational studies have consistently reported that a healthy diet is associated with better cognitive performance (Berendsen et al., 2017;Frith et al., 2018;Loughrey et al., 2017;Morris et al., 2015;Wengreen et al., 2013), but the evidence from clinical trials is more inconsistent (D'Cunha et al., 2018;Fitzpatrick-Lewis et al., 2015a;2015b;Forbes et al., 2015;Radd-Vagenas et al., 2018;Solfrizzi et al., 2018).
It is important to acknowledge that interventions

# WHO recommendations on a healthy diet
For adults, the WHO guidelines recommend the following.
A healthy diet contains:
- Fruits, vegetables, legumes (e.g. lentils, beans), nuts and whole grains (e.g. unprocessed maize, millet, oats, wheat, brown rice).
- At least 400 g (five portions) of fruits and vegetables a day. Potatoes, sweet potatoes, cassava and other starchy roots are not classified as fruits or vegetables.
- Less than 10% of total energy intake from free sugars which is equivalent to 50 g (or around 12 level teaspoons) for a person of healthy body weight consuming approximately 2000 calories per day, but ideally less than 5% of total energy intake for additional health benefits. Most free sugars are added to foods or drinks by the manufacturer, cook or consumer, and can also be found in sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates.
- Less than 30% of total energy intake from fats. Unsaturated fats (found in fish, avocado, nuts, sunflower, canola and olive oils) are preferable to saturated fats (found in fatty meat, butter, palm and coconut oil, cream, cheese, ghee and lard) and trans-fats of all kinds, including both industrially produced trans-fats (found in processed food, fast food, snack food, fried food, frozen pizza, pies, cookies, biscuits, wafers, margarines and spreads) and ruminant trans-fats (found in meat and dairy foods from ruminant animals, such as cows, sheep, goats, camels and others). It is suggested to reduce the intake of saturated fats to less than 10% of total energy intake and trans-fats to less than 1% of total energy intake. In particular, industrially produced trans-fats are not part of a healthy diet and should be avoided.
- Less than 5 g of salt (equivalent to approximately 1 teaspoon) per day and use iodized salt. 3. PUFA versus placebo (Forbes et al., 2015).
Vitamin B versus placebo (Forbes et al., 2015).
Vitamin E versus placebo (Forbes et al., 2015).
- Polyphenols versus placebo (Solfrizzi et al., 2018).
Protein supplementation versus placebo (Solfrizzi et al., 2018 were reported for all other cognitive outcomes (attention, working memory, processing speed, language and executive function) (Radd-Vagenas et al., 2018). A consistent positive effect of polyphenols on cognitive performance was also found, however, the quality of the evidence was low (Solfrizzi et al., 2018). Similarly, protein supplementations were found to have a beneficial effect on cognition in older adults, but the results were inconsistent and the quality of the evidence was low (Solfrizzi et al., 2018).
Overall, no effects were found for multi-complex (D'Cunha et al., 2018;Fitzpatrick-Lewis et al., 2015), vitamins B and E (Forbes et al., 2015), and PUFA supplementation (Forbes et al., 2015). Low-quality evidence was reported for protein and polyphenols supplementation (Solfrizzi et al., 2018)

# INTERVENTIONS FOR ALCOHOL USE DISORDERS BACKGROUND
Excessive alcohol consumption is common in many countries (Gell et al., 2015). In 2012, 5.9% of all deaths worldwide (about 3.3 million) were directly attributable to harmful use of alcohol (WHO, 2014). Furthermore, excessive consumption of alcohol is one of the leading causes of general disability globally (WHO, 2014), being a direct cause in more than 200 diseases including risk factors for dementia and injury conditions (WHO, 1992;

# WHO 2019a).
There is extensive evidence on excessive alcohol as a risk factor for dementia and cognitive decline (Langballe et al., 2015;Sachdeva et al., 2016;Zhou et al., 2014 The WHO mhGAP Intervention guide recommends the following:
Harmful use of alcohol
- Provide psychoeducation and emphasize that the level/pattern of alcohol use is causing harm to health.
- Explore the person's motivations for alcohol use. Conduct motivational interviewing.
- Advise stopping alcohol completely or consuming at a non-harmful level (if a non-harmful level exists) and indicate your intention in supporting the person in doing so. Ask the person if they are ready to try to make this change.
- Explore strategies for reducing or stopping use and strategies for reducing harm.
- Address food, housing and employment needs.
- Offer regular follow-up.

# Alcohol dependence
- Thiamine during alcohol use.
- Diazepam during alcohol detoxification to treat withdrawal symptoms.
- Naltrexone, acamprosate or disulfiram to prevent relapse after detoxification.
- Psychosocial interventions if available, e.g. cognitive behaviour therapy, motivational enhancement therapy, contingency management therapy, family counselling or therapy, problem-solving counselling or therapy; self-help groups.
Additional considerations include:

# SUPPORTING EVIDENCE AND RATIONALE
No systematic reviews were identified for interventions for hazardous and harmful alcohol consumption (behavioural, psychological and pharmacological interventions) and reduced the risk of cognitive decline and/or dementia.
However, a large body of observational evidence is available on alcohol as a risk factor for cognitive decline and dementia (Beydoun et al., 2014;Hersi et al., 2017;Ilomaki et al., 2015;Lafortune et al., 2016;Piazza-Gardner et al., 2013;Xu et al., 2017). Generally, single studies did not always show similar results
(mostly due to differences in study design) but the most consistent pattern is that of a U-shaped relationship between alcohol consumption and dementia and/or cognitive impairment, which clearly links excessive alcohol consumption to a significantly increased risk (Xu et al., 2017).
A range of adverse events has also been reported for Overall, the GDG concluded that the benefits outweighed the harms and, based on the strong observational evidence, made a conditional recommendation for interventions to reduce or cease hazardous and harmful alcohol use.
Adults with normal cognition or MCI Intervention:
- Cognitive stimulation

# - Cognitive training
Care as usual or no intervention Outcomes:

# COGNITIVE INTERVENTIONS
Dementia is preceded by cognitive decline. However, not everyone who is exposed to dementia risk factors will go on to develop cognitive impairment. The concept of cognitive reserve has been proposed as a protective factor that may reduce the risk of clinical onset of dementia and cognitive decline (Stern, 2012).
Cognitive reserve refers to the brain's ability to cope with or compensate for neuropathology or damage (Stern, 2012

# SUPPORTING EVIDENCE AND RATIONALE
For cognitive stimulation versus usual care or no intervention in healthy older adults, evidence was extracted from one systematic review (Strout et al., 2016). No evidence for adults with MCI was available.
The review reported that half of the interventions evaluated proved to be effective in improving cognitive outcomes in at least one cognitive domainexecutive function, attention, memory, language and/or processing speed (Strout et al., 2016). The quality of the evidence was low. The results were reported in narrative form and no meta-analysis was conducted. No evidence for incident MCI or dementia was available.
For cognitive training versus usual care or no intervention in healthy older adults, evidence was extracted from one systematic review (Chiu et al., 2017

# RECOMMENDATIONS AND CONSIDERATIONS
Cognitive training may be offered to older adults with normal cognition and with MCI to reduce the risk of cognitive decline and/or dementia.

# Quality of evidence: very low to low Strength of the recommendation: conditional
Adults with normal cognition or MCI

# Care as usual or no intervention
Outcomes:  (Cherry et al., 2011). Social disengagement conversely, has been shown to place older individuals at increased risk of cognitive impairment and dementia (Fratiglioni et al., 2004). A systematic review and meta-analysis of longitudinal cohort studies showed that lower social participation, less frequent social contact and loneliness were associated with higher rates of incident dementia (Kuiper et al., 2015).
The Lancet Commission on Dementia Prevention, Intervention, and Care identified social engagement as an intervention that could be used to prevent dementia (Livingston et al., 2017).

# RECOMMENDATIONS AND CONSIDERATIONS
There is insufficient evidence for social activity and reduction of risk of cognitive decline/dementia.

# SUPPORTING EVIDENCE AND RATIONALE
For preservation and promotion of social activity including community and family engagement versus care as usual or no intervention, evidence was extracted from one systematic review examining adults with normal cognition (Kelly et al., 2017 The GDG concluded that the evidence is limited and inconclusive, so no recommendation was made for social activity and risk of cognitive decline/dementia.
Furthermore, there is a risk of bias arising from reverse causality whereby low social engagement prior to diagnosis of cognitive decline or dementia may be at least in part due to the disease process. The GDG did not make a recommendation against social activity as they concluded that social activity has a wide range of other benefits to health and well-being.
Adults  (Chan et al., 1994), cancer (Renehan et al., 2015), premature mortality (Fontana & Hu, 2014), and CVD (Eckel, 1997), both as direct risk factors as well as risks for other cardiovascular risk factors, such as high cholesterol and hypertension.
Obesity has been steadily rising, particularly among older adults in the last few decades (Nguyen & El-Serag, 2010) and although an increasing body of evidence suggests that overweight (25 < BMI < 30) in older adults could be more protective than normal weight in terms of overall mortality (Flicker et al., 2010), a link has also been established between excess of fat body mass and cognitive impairment (Xu et al., 2011). A recent systematic review and meta-analysis of observational studies conducted on a total of about 600 000 individuals showed that obesity (but not overweight) at mid-life increases the risk of dementia (RR = 1.33; 95% CI: 1.08-1.63) (Albanese et al., 2017).
It has been suggested that weight loss could indirectly reduce the risk of dementia by improving a variety of metabolic factors linked with the pathogenesis of cognitive impairment and dementia (i.e. glucose tolerance, insulin sensitivity, blood pressure, oxidative stress, and inflammation) (Bennett et al., 2009). However, a direct beneficial effect of weight reduction intervention is also plausible. Although, so far, evidence of potential cognitive benefits of weight loss seem to be strongly associated with increased physical activity (Colcombe et al., 2006;Erickson et al., 2010), in 2011 a systematic review concluded that intentional weight loss can improve performance in some cognitive domains, at least in people with obesity (Siervo et al., 2011).

# Additional considerations include:
- Lifestyle interventions that included both diet and physical activity components seemed to show the best results.
- In addition to interventions at individual level, lifestyle interventions at the population level, such as activity parks, green spaces and infrastructure to support active commuting, need to be considered.
- Being underweight in both late-mid-life and old age might be associated with a higher risk of dementia.
However, it is likely that this association is explained, at least in part, by reverse causality, whereby brain pathology may cause weight loss before the clinical onset of dementia.
- Unintentional weight loss and malnutrition are associated with poor health outcomes and should be investigated and treated at all ages. However, it is unlikely that interventions that favour weight gain in people who are underweight in either mid-or late life can reduce the risk of dementia or cognitive impairment.
Interventions for mid-life overweight and/or obesity may be offered to reduce the risk of cognitive decline and/or dementia. WHO guidance on overweight and obesity should be followed.
- Advise overweight patients to reduce weight by following a balanced diet.
- Advise patients to give preference to low glycaemic-index foods (beans, lentils, oats and unsweetened fruit) as the source of carbohydrates in their diet.
- Advise patients to reduce sedentary behaviour and practise regular daily physical activity appropriate for their physical capabilities (e.g. walking). The GDG concluded that the benefits of the interventions outweighed the harms and provided a conditional recommendation. Since the observational evidence of a correlation between overweight/obesity and increased risk of dementia is stronger and more consistent in mid-life than in late life (Hersi et al., 2017;Lafortune et al., 2016;Pedditzi et al., 2016;Prickett et al., 2015;Xu et al., 2015), the GDG made a conditional recommendation for this population.

# RECOMMENDATIONS AND CONSIDERATIONS SUPPORTING EVIDENCE AND RATIONALE
Adults with normal cognition or MCI with hypertension
Antihypertensive medication, lifestyle interventions
Placebo/no intervention Outcomes:

# MANAGEMENT OF HYPERTENSION BACKGROUND
Hypertension in mid-life has been associated with an increased risk of late life dementia (Kivipelto et al., 2001). In particular, a pattern of increased blood pressure during mid-life followed by a rapid decrease in blood pressure later in life has been found in individuals who go on to develop dementia (Kivipelto et al., 2001;Launer et al., 2000;Stewart et al., 2009).
There is mixed evidence relating to the reduction of blood pressure in late mid-or late life and subsequent cognitive decline or dementia, however, there is evidence to show that the reduction of hypertension can have substantial benefits in reducing cardiovascular morbidity and mortality and thus improving overall health of the ageing population (Musini et al., 2009). Hypertension can be prevented through a range of lifestyle factors, including eating a healthy diet, maintaining a healthy weight and participating in an adequate amount of physical activity. It can also be controlled through antihypertensive medication.
However, the evidence for the effectiveness of blood pressure lowering treatments in reducing the risk of cognitive decline and dementia risk is mixed.

# RECOMMENDATION 1:
Management of hypertension should be offered to adults with hypertension according to existing WHO guidelines.

# Quality of evidence: low to high (for different interventions) Strength of the recommendation: strong

# RECOMMENDATIONS AND CONSIDERATIONS
HEARTS Technical package for cardiovascular disease management in primary health care: evidence-based treatment protocols

# Medications used to treat hypertension
- There are four main classes of antihypertensive medications: angiotensin converting enzyme (ACE) inhibitors; angiotensin receptor blockers (ARB); calcium channel blockers (CCB); and thiazide and thiazide-like diuretics. Any of these four classes of antihypertensive medication may be used unless there are specific contraindications. Proper treatment of hypertension usually requires a combination of hypertension medications.