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AN ACTION PLAN TO FACE THE CHALLENGE OF DEMENTIA: INTERNATIONAL STATEMENT ON DEMENTIA FROM IAP FOR HEALTH

 

H. Chertkow, on behalf of the Research Executive Committee of the Canadian Consortium on Neurodegeneration in Aging* and the International IAP committee on Dementia**

 

Corresponding Author: H Chertkow, 3755 chemin de la Côte-Ste-Catherine, Montréal (Québec), Canada, H3T 1E2, 514 340-8222, howard.chertkow@mcgill.ca

* The following individuals are members of the Research Executive Committee of the Canadian Consortium on Neurodegeneration in Aging: Drs. Howard Chertkow, Professor of Neurology, McGill University, Montreal, Canada; David B. Hogan, Professor of Geriatric Medicine, University of Calgary, Calgary, Canada; Sandra Black, Professor of Medicine, University of Toronto, Toronto, Canada; Howard Feldman, Professor of Neurology, University of British Columbia, British Columbia, Canada, and University of California, San Diego, San Diego, CA; Serge Gauthier, Professor of Neurology, McGill University, Montreal, Canada; Kenneth Rockwood, Professor of Medicine, Dalhousie University, Halifax, Canada; Mario Masellis, Associate Professor of Medicine, University of Toronto, Toronto, Canada; Katherine McGilton, Senior Scientist, Toronto Rehabilitation Institute, University of Toronto, Toronto, Canada; Mary C. Tierney, Professor, Department of Family and Community Medicine, University of Toronto, Toronto, Canada; Jane Rylett, Professor of Physiology and Pharmacology, Western University, London, ON, Canada; Dr. Pascale Léon, Lady Davis Institute, Montreal, Canada; Victor Whitehead, Lady Davis Institute, Montreal, Canada.

** The following individuals are members of the International IAP committee on Dementia: Ama de-Graft Aikins, Professor of Social Psychology, Dean International Programmes Regional Institute for Population Studies (RIPS), University of Ghana, Accra, Ghana; Liaquat Ali, Fellow, BAS and Vice Chancellor, Bangladesh University of Health Sciences, Dhaka, Bangladesh; Laila Asmal, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa; Hayrunnisa Bolay Belen, Professor of Neurology, Algology, Head of Algology, Director of Neuropsychiatry Centre & Director of Neuroscience PhD Program, Ankara, Turkey; Carol Brayne, Professor of Public Health Medicine, Director, Institute of Public Health, University of Cambridge, Cambridge, UK; Josef Priller, Deputy Director, Department of Psychiatry und Psychotherapy CCM, Charité – Universitätsmedizin Berlin, Germany; Lars Lannfelt, Professor, Department Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden; Alan Leshner, Chief Executive Officer, Emeritus, American Association for the Advancement of Science, Washington DC, USA; Ninoslav Mimica, Head of Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapče, School of Medicine, University of Zagreb, Zagreb, Croatia; Maryam Noroozian, Professor of Neurology, Founder & Director: Memory and Behavioral Neurology Division, Department of Psychiatry, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran; Adesola Ogunniyi, Professor of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria; Juha Rinne, Professor of Neurotransmission, University of Turku and Turku University Hospital, Turku, Finland; Paolo Maria Rossini, Full-Professor of Neurology, Chair of Institute of Neurology at the Faculty of Medicine, Catholic University, University Policlinic A. Gemelli Foundation, Rome, Italy; Jonas Alex Morales Saute, Neurogeneticist at Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Philip Scheltens, Director of the Alzheimer Centre, VU University Medical Center Amsterdam, Amsterdam, Netherlands; Ales Stuchlik, Head, Department of Neurophysiology of Memory Institute of Physiology, the Czech Academy of Sciences, Prague, Czech Republic.

J Prev Alz Dis 2018;5(3):207-212
Published online June 20, 2018, http://dx.doi.org/10.14283/jpad.2018.27

 


Abstract

An international committee set up through the IAP for Health met to develop an action plan for dementia. Comprehensive international and national initiatives should move forward with calls for action that include increased public awareness regarding brain health and dementia, support for a broad range of dementia research objectives, and investment in national health care systems to ensure timely competent person-centred care for individuals with dementia. The elements of such action plans should include: 1) Development of national plans including assessment of relevant lifecourse risk and protective factors; 2) Increased investments in national research programs on dementia with approximately 1% of the national annual cost of the disease invested; 3) Allocating funds to support a broad range of biomedical, clinical, and health service and systems research; 4) Institution of risk reduction strategies; 5) Building the required trained workforce (health care workers, teachers, and others) to deal with the dementia crisis; 6) Ensuring that it is possible to live well with dementia; and 7) Ensuring that all have access to prevention programs, care, and supportive living environments.

Key words: Risk reduction strategies, risk factors, life course, public awareness, national plans.


 

Introduction

This statement has been prepared by an international committee set up through the InterAcademy Partnership for Health (IAP-H), which is a component of the The InterAcademy Partnership (IAP). The InterAcademy Partnership (IAP) was launched in 2016, and currently has a membership of 135 academies of science, medicine and engineering from around the world. These include both national academies/institutions as well as regional/global groupings of scientists. This statement is modified from a position paper that was initially commissioned by the Canadian Academy of Health Sciences, and written, approved and submitted by the Research Executive Committee (REC) of the Canadian Consortium on Neurodegeneration in Aging (CCNA). Members of the Research Executive Committee of the CCNA and the International IAP committee on Dementia also appear at the end of the statement.
The proportion of the world’s population that is 65 years of age or greater has grown over the last number of decades, and this trend will continue. Advancing age is the greatest known risk factor for dementia (1, 2). If there is no change in age-standardized prevalence, societal aging is predicted to nearly triple the number of individuals living with dementia worldwide by 2050 (3, 4). It is estimated by that year the number of individuals with dementia will rise from 47.5 million people to an estimated 135.5 million with most of this increase occurring among people living in low- and middle income countries (2). Aside from the personal cost of dementia, these rising numbers will be associated with an economic burden. The 2015 global estimated cost of dementia was US $818 billion and is expected to be a trillion dollars by 2018 (5).
The World Health Organization (WHO) now recognizes dementia as a public health priority (6, 7). To respond to this challenge, a global series of actions initiated during the UK G8-Presidency in 2013 were undertaken by bodies such as the Organisation for Economic Co-operation and Development (OECD; (8)), Alzheimer’s Disease International (ADI) and by the World Dementia Council (WDC; (9)).

 

Dementia Overview

Dementia is an acquired, persisting and typically progressive decline in cognitive abilities, affecting learning and memory, language, and/or reasoning that is severe enough to interfere with independence in everyday activities. It becomes more common with increasing age during adulthood. Besides cognitive impairment, dementia is often associated with debilitating neuropsychiatric symptoms, such as agitation, psychosis, sleep disturbance, depression, anxiety and apathy (10). Dementia can arise from numerous conditions acting alone or in combination (11, 12). For many it is due to a neurodegenerative process, an umbrella term for a number of debilitating conditions that result in the progressive degeneration and/or death of neurons (5). Alzheimer disease is the most common neurodegenerative cause of dementia and is currently incurable. A mixture of brain diseases often underlies dementia, with many people showing changes consistent with both Alzheimer and cerebrovascular disease (13, 14). Dementia is usually a slowly progressive illness where the diagnosis is made after the process has been present for years (15).
Risk factors and conditions (such as smoking, or diabetes) commonly associated with vascular conditions (stroke, heart disease) are also known to be associated with dementia (16, 17). Frailty itself is a considerable risk factor for dementia (18). Parkinson’s disease is closely associated with the development of dementia (19). The majority of older individuals with dementia have mixed pathology in their brain (11, 12, 20, 21).
While young onset (under 60 years) dementia is seen infrequently in many countries, this may not be the case in countries with high HIV prevalence. The HIV epidemic is concentrated in younger people of low-income countries, particularly in Sub-Saharan Africa, where young people may subsequently bear a disproportionately greater burden of dementia (22).
Women are at both greater risk of developing dementia and then living longer with the condition after its onset (23). Women also provide most of the informal (unpaid) care for people living with dementia.
While there are currently no cures for the neurodegenerative conditions that lead to dementia, emerging research suggests that some life-style factors (e.g., engaging in physical activity, managing blood pressure, selected forms of cognitive training) may have the potential to delay, if not prevent, its onset (24-27). Population studies have suggested additional associated risk and protective factors, which require research to evaluate their potential as primary prevention intervention targets (28, 29). The progress to date in developing effective pharmacological treatment options has been disappointing (30-32), underscoring the need to understand better what contributes to the dementia syndrome in different generational cohorts as well as in different populations (33).
A key area for research and support is the development and dissemination of improvements for the care provided to people living with dementia including compassionate and appropriate end-of-life care (34-37). Greater acceptance and inclusion of people living with dementia within communities is increasingly seen as an important factor in improving their quality of life and minimizing disability (7, 38). The needs of patients and their families change along the course of dementing illnesses and it is necessary to gear support and therapy for the different stages of the disease.

 

A Call to Action

Because of these issues, developing a comprehensive strategy internationally to address the challenges of dementia will require wide consultation followed by the long term implementation of a comprehensive, integrated and responsive series of actions. Most initiatives will be nationally based, but additional international collaborations to address dementia will also be advantageous. The nationally based initiatives will generally share similar high-level goals and principles to address this global health problem. We call for countries within regions that have resources, to establish a network that can support other countries similar to them in their approach to dementia. The goals and principles of a call to action would include addressing the following broad areas: (a) Increasing public awareness – educating the general population about dementia, how to maintain brain health, and on the importance of addressing this health challenge, accepting people with dementia as they are, and accommodating to their remaining abilities; (b) supporting fundamental research to find and implement effective approaches (both pharmacological and non-pharmacological) to delay, prevent, slow down, treat, ameliorate, and eventually cure the common causes of dementia; (c) investing in national health care systems – this would entail both training a sufficient number and mix of providers as well as building the necessary infrastructure to ensure timely, competent person-centered care is available to those living with dementia and their caregivers through all stages of the illness.
Our Call to Action is one which aims at developing an evidence-based and a public health orientated approach. Ultimately, this should include a clear assessment for each population of the potential for primary prevention (upstream prevention), secondary prevention (early detection followed by effective treatment, considered to be likely more effective at that stage than later) and tertiary prevention (mitigation of dementia and its ramifications through various therapies and end-of-life care for those with dementia).

 

Elements of an Action Plan to Face the Challenge of Dementia

An action plan to face the challenge of dementia in its global context must include a concerted and coordinated series of actions from policies, to research, to care, to social  inclusion. Here are seven key elements of such an action plan.

National dementia plans must be established

National plans to combat dementia have been initiated in 29 countries/states since 2005. There is a global plan on dementia being developed by the WHO (6, 7) and the first regional plan on dementia in the Americas, published by the Pan American Health Organization (PAHO) in October 2015 (See the website of ADI https://www.alz.co.uk/dementia-plans/ for a list of national plans currently underway as well as countries currently lacking national plans). Canada is the only G7 country without a national dementia plan (39).
Each country should develop a national plan coherent with its health care goals which could coordinate activities, harmonize where appropriate with international efforts, promote the sharing of successful local initiatives, address identified gaps, ensure efficient use of resources, and mobilize further investment in all aspects of dementia including care and research. A national plan would acknowledge dementia as a public health priority and heighten awareness of this daunting health challenge.
As a first step, towards such plans, we propose that a national dementia status report should be carried out in as many countries with resources as possible. Such a status report for each region would be wide-ranging, including burden of all dementia types, comorbid disorders, risk factors, therapeutic approaches and care systems.
More research is necessary to establish the strength and interaction of lifecourse risk and protective factors relevant to dementia. Nevertheless, assessment of the “exposome”, potential risk and protective factors for each population, would be an important part of this report (40, 41). These should establish, for key lifestages, the balance in those populations of positive and negative features for brain health (42, 43). This would encompass a broad range of environmental factors such as maternal health, early life health, infections, education, vaccination, as well as adverse exposures such as poor housing, smoking, poor diet, and exposure to noxious substances.
A 5-year follow-up report should be planned to document the impact of national policies (public awareness, risk factors, care systems, etc.) and the creation of a national dementia strategy.

Increase investment in national research programs on dementia

The investment in medical research varies widely across countries. In 2016 the American investment in dementia research was US $936 million, which translates to US$2.93 per capita (23). In contrast, the Canadian investment in research on dementia was smaller (less than a quarter per capita of what is invested in the USA) (44). Overall, developed countries do not adequately invest in dementia research when compared to the funding of research on other conditions such as cancer and heart disease even though the cost of caring for persons with dementia is estimated to be greater than that for dealing with either of the other two conditions (45, 46). It has been stated that a goal of 1% of the national annual cost of dementia should be steered into dementia research programs (Dementia in Canada: A National Strategy for Dementia-friendly Communities, Report from Canadian Senate, 2016 (6)). This additional investment in each country will have to be thoughtfully allocated and managed. Broad coordination within each country should be organized for best use of research funds. Governance and prioritization of dispersal of these funds must also involve individuals living with dementia and their caregivers, the research community, and practitioners.

This investment must span all aspects of dementia research

Allocated research funds should support a broad range of activity from biomedical investigation to inquiries dealing with clinical aspects, health systems and services research. There must be fundamental research to unveil the mechanisms involved in the onset of neurodegenerative diseases and hopefully pave the way to a specific and effective pharmacological treatment. In addition, research to gain better insight into understanding the social cultural and environmental factors that affect the health of populations is essential. Investments should target national research capacity, supporting knowledge transfer, addressing the needs of unique populations (for example, indigenous people and those living in rural and remote communities (47-49)), investigating sex and gender differences in dementing conditions, and embracing ethical and social dimensions (50, 51).
There is now considerable potential for earlier diagnosis of various forms of dementia using clinical, imaging, and biomarker support (52). The advantages and potential of early diagnosis is a critical focus of research in Western countries (53-57). Attention must now be paid to delineating the optimal approaches to early diagnosis and establishing the risks and benefits of translating this knowledge into health care policy.
The neuropsychiatric (behavioral and psychological) symptoms of dementia need more attention given their strong impact on quality of life, caregiver burden and rate of institutionalization (10, 58, 59 60). Future research into the prevalence, etiology and therapy (including randomized controlled trials) of neuropsychiatric symptoms of dementia is needed.
There must be research investment into understanding what combinations of modifiable lifestyle factors across the lifecourse increase and decrease the risk, of developing dementia with aging (26, 61). This is not a one-size-fits-all syndrome across the globe. The combinations of relevant risk factors may vary in different cultures and communities. The most effective preventative and public health strategy for dementia will only emerge when the fullest understanding of these factors is achieved.
Specific attention should be devoted to the support of social research aimed at identifying the actual needs of subjects with dementia and their caregivers (62-64). The general purpose of such investigations would be the planning of multifaceted interventions encompassing environmental, psychological, medical and social support.

Risk reduction strategies should be instituted

While there is still a considerable amount to learn about the full interplay of risks, governments must support national risk reduction and empowerment strategies for the public and support the efforts of health professionals to promote healthy brain aging. Current evidence can be used to empower the public and health professionals to act in ways that will reduce the risks of all dementia types developing, postponing the appearance of their clinical manifestations, and optimizing everyday functioning in meaningful social activities and roles. The focus of such risk reduction would include treatment and prevention of vascular risk factors – hypertension, obesity, diabetes, smoking, and high-calorie diets, and treatment of HIV to prevent HIV-related dementia. It would also include risk reduction to address sleep problems, illiteracy, head trauma, malnutrition, and physical inactivity in addition to other region-specific risk factors (5).
Risk reduction at the individual level must be supplemented by evidence-based structural and legislative alterations that support these reductions. Smoking legislation, strategies for excessive alcohol risk reduction, reduction of dietary salt, legislation to reduce head injuries are only a few of the risk reduction strategies that can be undertaken by governments to affect the occurrence of dementia in the population. Such governmental interventions will lead to less inequality because they benefit the disadvantaged as well. The  WHO Global Noncommunicable  Diseases Action Plan 2013-2020 focuses on many of these elements (6).

The required workforce must be planned and trained

Workforce requirements to deal with the increasing number of persons with dementia must be determined and steps taken to ensure the required workforce is both trained and supported in their activities. A well trained and supported workforce of the right mix and number to deal with the needs of this emerging population is required. In each country, a national workforce plan will have to be created and implemented with the active involvement of local and regional authorities.
The full breadth of necessary trainees will only emerge after appropriate evidence-based strategies for risk reduction emerge. The workforce trained will initially be focused on the elderly, and the health care sector, but addressing modifiable risks (for example, limited education, early childhood nutrition) implies an investment in teachers, nutritionists, and a host of other professionals in the future.

We must ensure that it is possible to live well with dementia

When a diagnosis of dementia is made, an individual should not be constrained to abandon her/his social role and participation. Creating the conditions within a country where one can live well with dementia includes ensuring that the public is aware of dementia in all its complexity, that there are accommodations in the environment (including work) to compensate for changing abilities, that there is adequate protection against abuses of all kinds against individuals living with dementia, and legal that rights are not automatically withdrawn from people living with dementia. Cooperation between academies and local administration should be encouraged so that all the needs of persons living with dementia and of their caregivers can be assessed and met.

Access to prevention and care should be made available to all

To the extent possible, access to preventive programs, systems of care, and supportive living environments should be made available to all citizens with, or at risk of, dementia (49, 65-67)

 

The Future of the Dementia Challenge

Dementia will be part of the global landscapes for many decades, reaching levels that are at least twice the current 2016 values. Indeed, even if research could provide the means of eradicating brain diseases causing dementia tomorrow, numerous individuals would already be on the trajectory to dementia. Brain diseases causing dementia are now known to start many decades before any clinical signs. For these reasons, a total solution will not be available for some time to come. This is why the member Academies of IAP for Health are focusing attention on the necessity of engaging in an action plan for dementia which is balanced and designed to address all aspects of the challenge, especially the wellness of those living with dementia and their caregivers.

 

Conflict of interest: Dr. Chertkow reports grants from the Canadian Institutes of Health Research (Foundation grant) and the Weston Foundation (Canada). He also reports clinical trial conduct-related fees from TauRx, Hoffmann-Laroche, and Merck Inc. In addition, he reports indirect support from the Alzheimer Society of Canada (funding partner of the Canadian Consortium on Neurodegeneration in Aging). No other disclosures relevant to the manuscript.

Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

 

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PRIMARY PREVENTION OF DEMENTIA: AN EPIDEMIOLOGICAL POINT OF VIEW

 

C. Berr

 

Corresponding Author: Claudine Berr, INSERM Unit1061, «Neuropsychiatrie: Recherche Epidémiologique et Clinique», Hôpital La Colombière, 39 Avenue Charles Flahault, BP 34493, 34093 Montpellier Cedex 5, France, Tel : 33 (0) 4 99 61 45 66    Fax : 33 (0) 4 99 61 45 79, claudine.berr@inserm.fr

J Prev Alz Dis 2016;3(3):160-163
Published online June 14, 2016, http://dx.doi.org/10.14283/jpad.2016.103


Abstract

From an epidemiological perspective, in order to increase the level of evidence, it is necessary to refer to data from longitudinal studies to validate the temporal relationship between exposure (e.g. the behavior or modifying factor) and the disease. Findings from such studies are useful for defining risk factors and laying the groundwork for proposing interventions for prevention. This step is crucial in order to define the periods (life-course approach) and groups at risk, which will then become the targets of interventions designed to modify behaviors or lifestyle. Specifying the underlying mechanisms of these risk factors is one of the objectives of etiological epidemiology which focuses on the origin of diseases but is not essential for a more pragmatic interventional approach. These questions are essential for dementia prevention and are discussed in this paper. Furthermore, timing interventions is a major problem even if we identify primary prevention pathways in dementia. Another important concern for epidemiologists is the need to make projections to estimate the number of dementia cases in the next decades considering different intervention scenarios. These models require adequate descriptive indicators of dementia, demography and mortality and precise estimations of the impact of potential interventions in terms of delaying disease onset for instance.

   
Key words: Epidemiology, causality, pragmatic approach, life-course.


 

Introduction

Modern medical practice must be backed up by evidenced-based medicine (EBM), defined as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care management of individual patients”. The practice of evidence-based medicine means associating individual clinical expertise with the best available external clinical evidence from systematic reviews, with randomized clinical trial (RCT) being the gold standard (1).
The two main objections to EMB are: 1) in many cases, the evidence is missing, yet the absence of proof of the treatment’s effectiveness does not mean that this treatment is not effective; 2) it is difficult to apply to one single patient the conclusions of a general study. The results from RCT and meta-analyses demonstrate the compared effectiveness of a treatment for a “medium” or “standard” randomized patient. This patient is not necessarily similar to the real patient that we see in clinical practice, especially in older patients with dementia or suffering from multiple pathologies. Furthermore, these studies do not reflect the important events that occur after randomization and trigger changes in the treatment itself or the patient’s behavior. This element is particularly relevant when the analysis is based on demented subjects and non-pharmacological therapies.
On an epidemiological level, in order to improve the level of evidence, it is necessary to refer to data from longitudinal studies (cohort studies) to validate the temporal relationship between exposure (e.g. the behavior or modifying factor) and the disease or its evolution. The results help defining risk factors or protective factors (2) and lay the groundwork for proposing interventions for primary, secondary or tertiary prevention. This step is crucial in order to define the periods and groups at risk, which will then become the targets of interventions designed to modify behaviors. It is important to take this step into account when making projections on the number of dementia cases for the next decades, while including hypotheses for prevention.

 

Prevention bases

With the first official definition of healthcare prevention (3) “all the measures intended to avoid or reduce the number and severity of diseases, accidents and disabilities.”, the WHO proposes a classification for prevention of diseases and healthcare disorders according to the moment when the prevention is implemented: primary prevention relates to all activities aimed at «reducing the incidence of a disease within a population and therefore reducing, whenever possible, the risks of new cases»; secondary prevention relates to all activities aimed at «reducing the prevalence of a disease, such as early screening procedures and appropriate treatment to reduce the time of evolution, risk or chronicity or recurrence», and tertiary prevention relates to all activities aimed at “reducing the damage caused by the disease, its recurrences and related disabilities” (4). Even though other definitions and classifications exist (5), the WHO classification is the most universally accepted.
Primary prevention can be defined as all the activities aimed at reducing the incidence of a disease, therefore reducing the onset of new cases or delay the age of onset which can also be very important for pathologies where frequency is related to age, such as Alzheimer’s disease. In the general population, this type of prevention takes into account individual risk factors or behaviors as well as environmental and social risks. By acting upstream, this prevention prevents or delays the onset of the disease. Specifically it uses different strategies to inform the population: healthcare education, diet and nutrition enhancement or environment improvements (4, 6). At first, this primary prevention requires to identify, with a good level of evidence, factors that might alter the incidence of the pathologies (risk factors and protective factors). With the advent of biomarker testing and the changing diagnostic landscape of Alzheimer’s disease, the distinction between primary and secondary prevention has evolved and is considered less clear (7).

 

How to identify primary prevention pathways in dementia?

The cornerstone of epidemiology is the notion of risk factors best identified in cohort studies. This approach allows the implementation of refined interventions targeting any risk factor (e.g. demographic, social, economic, income-related, work conditions-related, physical activities, intellectual activities, social activities, related to the individual or collective environment, access to healthcare, prevention and home environment).
Refining the underlying mechanisms of these risk factors is one of the objectives of etiological epidemiology which focuses on the origin or diseases but is not essential for a more pragmatic interventional vision.  Do we always need to know the origin of a disease to act on its incidence or progression? Is it essential, before thinking of implementing an intervention, to understand the mechanisms underlying the relationship between the modifying factor and the disease? These questions are essential and there is no unique answer. In social epidemiology, understanding causality is a crucial step in defining the target population (8).Yet a pragmatic approach could be to intervene on the most easily accessible and modifiable risk factors in the causal chain.
It might be legitimate to want to understand this, yet what is important for the individual and for society as a whole is to have an effective action to prevent a disease or slow down its evolution. The investigator must collect all elements needed to implement a clinical trial under the best conditions: choosing the nature of the intervention, population, time period and duration of the trial. Beforehand, confronting the results from observational studies obtained in different conditions is a necessary step to collate the various elements needed to prepare an intervention project. Today there are several meta-analyses that enable a rational and objective analysis of the existing studies in a given field. Various components must be assessed to better refine the best intervention pathways:
a) Highlighting risk factors (increasing the probability of incidence of a disease) or protective factors (decreasing this probability) is the first step to defining intervention pathways if these factors can be altered. The reproducibility of results and validating the association with the different levels of activity (dose effect) are essential elements just like confounding factors.  The nature of the intervention will then be guided by preliminary observational studies. The choice of the population observed is important in order to be able to generalize the results and propose an intervention. If the subjects included have too many characteristics (selection bias), or if the subjects followed differ from those who are not (attrition bias), it will be difficult to extrapolate the results (9).
b) At which point during the course of a lifetime, should the factor be modified in order for a potential intervention to be effective? This question is essential when looking at pathology with an age-dependent frequency such as dementia. In epidemiology, the life course approach gives us elements to better understand the difficulties involved with the care management of alterable factors that can be present early on in life and will be modified during the life course.
In the study of aging (10), this life course approach had for objectives to integrate the different biological, social, clinical psychological and environmental components that interact all along the lifetime of a person, including early life experiences, in order to promote healthy aging and delay the emergence of frailty and chronic diseases (11, 12). A certain number of elements are identified as positively or negatively influencing the life course: life events, health problems, psychological distress and financial insecurity. In social sciences, the notion of life course (13) brings up questions regarding changes to individual trajectories, which are triggered by society’s evolution. Thus, the behavior of an individual (and of course the person’s health behavior) varies according to the lived-in time period in history. From then on we are looking at the idea that risk factors can constitute causality chains, in which a pragmatically accessible link can be chosen for an intervention.
Another difficulty encountered in primary or secondary prevention studies, is the need to implement them early on in the life course of the subject, a late intervention having less chances of being effective, with a follow-up period that is long enough to observe the potential effect of the intervention (14). Furthermore, to be effective, interventions must be conducted on the long run and/or have effects that linger due to the behavioral changes they might induce. Major limitations are the practical and financial constraints that may limit the duration of these clinical studies and follow-up of subjects. If the effects of the intervention are only measurable when implemented over a long period of time, then the feasibility of the study must be questioned and randomization will be even more difficult. Interventions that last for a long period of time might induce an intergroup contamination effect, since the control group (no intervention) might more easily modify its behaviors. Furthermore, intervention compliance might “loosen up” over time. This limit should be specifically considered for all interventions aimed at modifying diet or physical activity habits.

 

If we manage to implement an effective intervention, which effects on the number of cases to come will we observe?  

When we try to estimate the number of dementia cases, we need to know 1) demographics with age and gender repartition of the given population; 2) incidence of dementia and mortality related to the disease. The number of cases can be influenced by the variations of the incidence and any preventive intervention implemented to decrease the incidence or delay the age of onset of the disease.
In a previous paper  we aimed to estimate the projections of the number of cases of dementia until 2050 in France and in the 27 EU countries by using a model that took into account dementia incidence and mortality (15). Projections of age-specific prevalence require knowledge of age-specific incidence rates and of future population sizes and mortality rates for both demented and non-demented individuals. We tested the robustness of these estimates using different hypotheses taking into account estimates of alternative incidence and scenarios for life expectancy or using the hypothesis that a preventive intervention that delays the age of onset of the disease is put in place.Our estimates are based on a model using the European incidence data for dementia by age and sex, the relative mortality risks related to dementia stratified by age classes, and the projections of mortality coefficients in the French and European population.
According to these analyses, 754000 people were affected by dementia in 2010 in France, 72% were women. This total number of dementia cases amounted to 1.2% of the total population, 7.9% of the population over 65 years of age, and 2.8% of the active population. In 2050, 1.813 million of people will be affected by dementia, 68% will be women. This total number of dementia cases correspond to 2.5% of the total population, 9.6% of the population over 65 years of age, and 6.2% of the active population. For the 2010–2050 range, the number of dementia cases is multiplied by 2.4, amounting to an average increase of 2.2% per year over 40 years. This is not a linear change, it could be affected by several periods of acceleration and slowing down as various birth cohorts arrive in the age groups bearing a high incidence of dementia. An intervention implemented in 2010, triggering a decrease in the incidence of dementia would show an impact 5 years later. Delaying the onset of dementia cases, overall or specifically for AD by 1, 2 or 5 years would reduce the prevalence of these diseases in the medium and long term by about 10%, 20%, and 50%, respectively. For example, if the onset of the disease is delayed by 2 years, the number of dementia cases in 2030 will be reduced from 1.13 to 0. 987 million and in 2050 it will go down from 1.813 to 1.431 million.
Of course these numbers greatly depend on the models used and data considered for dementia incidence. When accounting for the difference between the mortality of the general population and the mortality of non-demented subjects (16) and under the assumption that life expectancy will increase by 3.5 years for men and 2.8 years for women by 2030, the number of subjects with dementia was estimated to increase by about 75 % from 2010 to 2030 with a 200 % increase after 90 years of age. In this model, a therapeutic intervention on the whole population reducing high blood pressure prevalence would lead to a decrease in both dementia incidence rates and mortality but would have a modest impact on the number of dementia cases.
At the USA and worldwide scales, using the population-attributable risk, Barnes and Yaffe (17) computed the number of dementia cases that could be prevented by reducing the prevalence of cardiovascular and lifestyle risk factors (diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity). They projected the effect of risk factor reduction on AD prevalence by calculating population-attributable risks (the percentage of cases attributable to a given factor) and the number of AD cases that might be prevented by risk factor reductions of 10% and 25% worldwide and in the USA. Together, up to half of AD cases worldwide (17.2 million) and in the USA (2.9 million) are potentially attributable to these factors. A 10–25% reduction in all seven risk factors could potentially prevent as many as 1.1–3.0 million cases worldwide and 184 000–492 000 cases in the USA alone.

 

Conclusions

The life course model underlines that the situation and difficulties encountered by a person were preceded by cumulated biological and social disadvantages. If the life course was an accumulation of disadvantages, efforts to repair these damages will have to be important. The life course model shows that sometimes interventions must focus on fundamental causes or should be conducted on the very long term. Moreover, dementia being a chronic disease with a very long and progressive pathological process (18) it is unlikely that late changes in risk factors have a great impact on dementia risk. Epidemiology and experimental evaluation models can only report interventions on a time-scale of a few years. This is probably the core of the difficulties and failures encountered in dementia prevention studies.

 

Conflict of interest: No conflict of interest.

 

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