Introduction

During the World Health Assembly in May 2022, the World Health Organization (WHO) introduced the new Intersectoral Global Action Plan (IGAP) on Epilepsy and other Neurological Disorders 2022–2031 (ref. 1). By setting out strategic objectives and targets, and outlining the means to verify the achievement of these targets, this plan provides an integrated approach to tackle the global burden of neurological conditions. The IGAP aims towards a world in which “brain health is valued, promoted, and protected across the life course; neurological disorders are prevented, diagnosed and treated, and premature mortality and morbidity are avoided; and people affected by neurological disorders and their carers attain the highest possible level of health, with equal rights, opportunities, respect and autonomy”1. This plan marks a new paradigm for neurological disorders and neurology, which could be revolutionary if combined with the innovative concepts of holistic, spiritual2 and planetary3 health. Co-design1,4,5 and co-implementation of these solutions will be vital to achieve equitable and inclusive access to services for the promotion, protection and recovery of brain health in all human populations across the life course.

In this Perspective, we highlight the global burden of neurological disorders and describe the specific features of this burden in certain groups and populations. We also discuss definitions of brain health and introduce the concept of the neurological quadrangle, which encompasses surveillance, prevention, acute care and rehabilitation, as a framework to implement the WHO IGAP to improve brain health and wellbeing across the lifespan. The fundamental role of brain health in achieving the Sustainable Development Goals (SDGs) set out by the United Nations (UN) as a call to action to address poverty, inequality and climate change, among other issues, is also discussed, with a particular focus on the third SDG on health1,6. Perhaps most importantly, given the increasing prominence placed on the interconnectedness of all life forms and a holistic approach to health, including spiritual and social health — by the WHO IGAP and the COP26 Special Report on Climate Change and Health, among other movements1,7,8,9,10 — we articulate an integrated holistic approach to brain health. We recommend synergistic action, which must not only leverage new scientific evidence and technological innovation but also build a broader coalition of stakeholders, including the six Ps: patients, healthcare service and product providers, policymakers, payers (funders of health care), implementation partners and the general population. This multisectoral approach will use a quadruple helix comprising academia, policy-makers, the private sector and the population.

The global burden of neurological disorders

The increasing burden

Neurological disorders, including all disorders of the brain, cranial nerves, spinal cord, peripheral nerves and neuromuscular systems, are highly prevalent: at least one in three people will have a neurological disorder at some point during their lifetime11. Between 1990 and 2016, neurological disorders were the leading cause of disability-adjusted life years (DALYs) and the second largest cause of deaths globally, accounting for nine million deaths per year12. Owing to their immense and growing burden relative to other diseases, neurological disorders should be prioritized at the local and global levels by all stakeholders, particularly health-care providers and policy-makers, to maximize benefits for directly affected individuals and to aid prevention in the wider population. In 2016, the top five neurological causes of DALYs globally were stroke (42.2%), headaches (migraine, 16.3%), dementias (10.4%), meningitis (7.9%) and epilepsy (4.9%)12. Of nine million global deaths in 2016, the three leading neurological causes among 15 neurological disorders that were assessed were stroke (67.4%), Alzheimer disease and other related dementias (20.3%) and meningitis (3.7%)11,12. Other common neurological disorders included in the assessment were Parkinson disease, encephalitis, spinal cord injuries, traumatic brain injuries, multiple sclerosis, CNS cancers, cervical and lumbar spondyloses, motor neuron disease, peripheral nerve and neuromuscular diseases and tetanus and other neuroinfectious diseases11. In addition, inherited neurometabolic diseases comprise more than 1,400 different genetic diseases and together pose a substantial burden, with a cumulative incidence ranging from 1 in 800 to 1 in 2,500 newborns13.

Huge direct and indirect costs are incurred from neurological diseases. For example, stroke, as the leading neurological cause of death and disability, costs almost US $900 billion per annum globally14, and dementia cost US $1.3 trillion in 2019 (ref. 15). Poor sleep and sleep–wake disorders, which affect over 20% of the general population16, are associated with reduced functioning and wellbeing and are estimated to result in economic costs of nearly US $700 billion annually across five Organization for Economic Cooperation and Development countries (Canada, USA, UK, Germany and Japan)17. In addition, sleep disorders are associated with an increased risk of develo** neurological and mental health problems such as stroke, neurodegenerative disorders and depression18,19,20,21,22 and have been reported to aggravate the course of other neurological disorders, including epilepsy, migraine, neuroimmunological disorders and pain conditions18. This impact of sleep disorders on other neurological conditions could, therefore, result in further indirect costs.

Studies examining the comparative costs between neurological disorders and other diseases in Europe and the USA further highlight the economic burden of neurological disease23. The cost of neurological disorders in Europe was estimated at €798 billion in 2010, 63% of which were indirect costs24. This total was equivalent to the cost in Europe of heart disease, cancer and diabetes combined. Similarly, a US study reported an annual cost of US $789 billion from nine major neurological disorders in 2014 (ref. 25). Both studies concluded that, to prevent the financial burden becoming unmanageable, neurological disorders require investment and focus equivalent to that received by cancers and heart disease. In many countries, particularly low-income and middle-income countries (LMICs), a lack of universal health coverage further increases health-care and social-care costs. However, a lack of studies investigating the burden of neurological disorders in LMICs hinders the ability of governments to leverage change23. The growth of the ageing population will create an increasing demand for treatment, rehabilitation and support services for people with neurological disorders, resulting in an even larger financial burden. In addition, compared with other non-communicable diseases (NCDs) such as heart disease, cancers and diabetes, many neurological disorders have few established modifiable risk factors; more investment in neurological translational research is therefore necessary to unravel more risk factors and develop effective targeted prevention and treatment strategies23.

The NCDs Countdown 2030 report stated that the risk of dying from neurological disorders from birth to 80 years of age increased in more than half of all countries from 2000 to 2016, making them the fastest-growing cause of death among NCDs26. Estimates suggest that at the current growth rate, only 23% of the burden from neurological disorders can be prevented by 2040, and within this time frame, DALYs attributable to neurological disorders are expected to increase by 50% (ref. 27). The implication of these estimates is that if efforts are not accelerated, neurological disorders will cause an even greater burden than we currently face, especially in populations that are currently affected the most, as discussed subsequently27.

Priority groups and populations

The burden of neurological disorders in certain groups and populations deserves dedicated attention to foster inclusiveness and equity and to maximize the global impact of interventions. Women represent the majority of caregivers for patients with a number of neurological disorders28,29,30, which can cause substantial financial and emotional burden. The burden of paediatric neurological disorders also demands attention because of the potential deleterious effects on the develo** brain. Survival with these disorders is improving as a result of better general care and the increasing availability of disease-modifying treatments; however, the burden on the child, parents and caregivers, and society in general, in terms of DALYs and costs, remains extremely high31. For example, children who survive brain tumours often need lifelong socioeconomic support as they can have a considerably reduced earning capacity in adulthood and higher somatic health-care costs than healthy, age-matched comparison individuals32. Elderly individuals also have a high burden of neurological disorders; in particular, stroke and neurodegenerative diseases. Furthermore, elderly individuals are at an increased risk of having comorbidities of two or more neurological diseases, such as stroke–epilepsy–dementia, Parkinson disease–dementia or stroke–dementia, as well as other NCDs such as spondylosis, osteoarthritis and benign prostatic hyperplasia.

The burden of many neurological disorders is much heavier in LMICs than in high-income countries (HICs)33. For example, 80% of the burden of stroke is borne by LMICs, with age-standardized stroke-related mortality and DALYs being almost four times higher than those in HICs in 2019 (ref. 34). Stroke frequently affects individuals in LMICs during their working years, and for those who survive, many are unable to return to work or have reduced capacity for work34. The high burden of stroke in LMICs is attributable to reduced access to stroke prevention, acute treatment and rehabilitation services35. Epilepsy also disproportionately affects people living in LMICs, accounting for around 80% of cases worldwide, largely owing to preventable causes, including perinatal injury, infection and brain trauma12,36. In addition, LMICs have a substantial burden of dementia; for example, in 2015, an estimated 2.13 million cases of dementia occurred in sub-Saharan Africa, resulting in an estimated cost totalling US $6.2 billion37. Although the incidence and prevalence of some neurological disorders such as stroke have been declining in HICs over the past few decades, cases have been persistently rising in most LMICs38. The demographic transition owing to increasing age of the general population is expected to further exacerbate the burden of neurological disorders that are more common in elderly individuals, especially in LMICs. Similarly, related economic and epidemiological transitions are likely to worsen the burden of neurological disorders more severely in LMICs than in HICs39.

Despite the high burden of neurological disorders in LMICs, the global dearth of neurologists is more pronounced in these countries, with only three adult neurologists per ten million people, in contrast to 475 adult neurologists per ten million people in HICs40. African countries are particularly affected: in sub-Saharan Africa, the estimated ratio of child neurologists is 0.01 per 100,000 people, and 27 of 54 African countries do not have a single child neurologist (J.W. and C.E.C.-B., unpublished data). An inadequate number of neurology training programmes and emigration of highly qualified individuals — the so-called ‘brain drain’ — also contribute to the shortage of neurologists in LMICs.

In many LMICs, the direct and indirect costs of medical treatment incurred by individuals are high, leading to catastrophic out-of-pocket expenditure that further aggravates the vicious cycle of poverty and disease. For instance, every year, 55 million people in India fall below the poverty line as a result of health-care costs41. Other challenges in LMICs that increase the burden of neurological disorders include overpopulation and a lack of material resources such as drugs and medical equipment. Most LMICs spend less than 3% of their gross domestic product on public health42, and only small proportions of this percentage go towards brain health. LMICs are struggling to provide not only therapeutic care but also surveillance, diagnostic, prognostic, preventive, rehabilitative and palliative services to people with neurological disorders11,26,43. Non-inclusion of people living in LMICs in clinical trials presents another challenge, especially given the biological and non-biological variability in disease characteristics between countries. In addition, in many LMICs, there is a lack of awareness and widespread social stigma about neurological disorders, which can prevent individuals from seeking medical care44,45. Moreover, LMICs are particularly vulnerable to the effects of climate change and to air and water pollution, all of which can affect brain health3. Compared with HICs, LMICs experience slower progress in prognosis, diagnosis, treatment and care of all NCDs46, which makes tackling the growing burden of neurological disorders in these countries a formidable challenge. Notably, underserved communities and ethnic minorities in HICs also face many of the challenges mentioned earlier, especially populations affected by colonization, slavery and systemic racism.

Neurological disorders and brain health

In addition to their epidemiological importance, neurological disorders are major determinants of brain health, as well as overall health. There is no consensus definition of ‘brain health’ and no universally accepted objective measure of brain health across the life course. Nonetheless, various researchers and organizations47,48,49,50,51,52,53 have proposed definitions emphasizing the various domains of brain health (Table 1).

Table 1 Definitions of brain health
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One study used a multistaged concept analysis method consisting of a literature review and an international survey, with a final analysis to integrate the findings into a working definition of brain health. Chen et al.50 proposed the definition of brain health as “a lifelong dynamic state of cognitive, emotional, and motor domains underpinned by physiological processes; it is multi-dimensional and can be objectively measured and subjectively experienced; brain health is influenced by eco-biopsychosocial determinants, resulting in a continuum of quality of life and wellness.” This definition underscores the multidimensional nature of brain health, including the inherent difficulties of measuring it empirically, given that it is subjectively experienced, the fact that it is affected by several factors and its impact on the quality of human life50.

Modelling their own definition after the WHO definition of health, Hachinski et al.52 proposed a definition of brain health in adults as the “state of complete physical, mental, and social wellbeing through the continuous development and exercise of the brain.” In the 2022 position paper of WHO51, brain health is defined as “the state of brain functioning across cognitive, sensory, social–emotional, behavioural and motor domains, allowing a person to realize their full potential over the life course, irrespective of the presence or absence of disorders.” The WHO definition recognizes that brain health encompasses neural development, plasticity, functioning and recovery across the lifetime of an individual51,54.

Further to the definitions mentioned earlier, brain health also involves protection and promotion of brain function and is important for total and spiritual wellbeing. Spiritual wellbeing involves finding and living one’s life purpose and understanding the values and beliefs that guide one’s actions8,9. According to the seed of life model, which proposes a dualistic configuration of the human being comprising both a physical and spiritual domain referred to as spheres9, the spiritual sphere involves a relationship with the transcendental and idealistic aspects of life, including connection to others and the meaning of life9, but is not the same as religiosity8. Spiritual wellbeing can have a positive effect on brain health, mental health and overall physical health10, which in turn could have positive effects on social and planetary health.

A 2018 article by Bradley et al.55 set out to conceptualize a new definition of health that takes into account the body, mind and spirit. The authors drew on lessons from the Ancient Greeks, including Aristotle, who “saw that the striving of humanity was towards being well — a physical, mental and spiritual state where life flourished.” The definition from Bradley et al.55 describes health to be a dynamic quality of living, rather than a static state of being, that allows individuals to live a fulfilled life by fully using their body, mind and spirit each day. A quote from the Greek physician Herophilus stated that “when health is absent, wisdom cannot reveal itself, art cannot manifest, strength cannot fight, wealth becomes useless, and intelligence cannot be applied”55. This fundamental role of health in all aspects of human life is illustrated by the experience of the COVID-19 pandemic, which grounded the economy and major sectors of human activities, leading to unprecedented challenge to food systems, the working world, human travel and transportation of goods and considerable social disruption and insecurity56.

Spirituality, including a sense of purpose and meaning in life8,9,10, has been associated with prevention and better outcomes of dementia and other neurological diseases9,57,58,59. A systematic review identified several brain regions potentially associated with spirituality and religious practices and beliefs, including the medial frontal cortex, orbitofrontal cortex, precuneus, posterior cingulate cortex and caudate nucleus57,60. Scientific exploration and characterization of these brain regions could involve functional and anatomical map**, trans-omic studies, functional imaging, neurophysiology, brain–computer interfaces, brain stimulation and computational neuroscience. Exploration of these brain regions could help us to unravel and harness spirituality for clinical interventions against various disorders, including mood, anxiety, psychotic, pain and vertiginous disorders57,60. Thus, both biophysical and psychospiritual models should be incorporated in defining brain health.

On the basis of the definitions and ideas discussed earlier, brain health can be described as the complete functioning of the brain across the life course to support the full physical, mental, social and spiritual wellbeing and quality of life of an individual towards attaining and maintaining the epitome of a meaningful, impactful, purposeful and productive life (Fig. 1). Brain health is essential for brain skills, which are in turn central to the development of brain capital and a brain economy, that is, an economy that demands cognitive, emotional and social skills over manual skills61. Brain capital encompasses the creativity, knowledge and skills that individuals accrue and improve on during their lifetime, which enable them to realize their potential and contribute productively and meaningfully to the economy and society at large61. Promotion and protection of brain health are central to the development of brain capital, which is itself essential for human capital development. Indeed, brain health is necessary for the attainment of the third SDG on health6 (Fig. 2), which is central to the attainment of all other SDGs1,6. To promote brain health, in 2021, the European Academy of Neurology launched a Brain Health Strategy to support 47 national neurological societies across Europe in the implementation of the WHO IGAP, alongside other national brain health campaigns62. Moreover, especially in LMICs, brain capital is an asset and resource that can be developed at a time when natural resources are dwindling, the knowledge economy is growing and the world is moving towards a brain economy.

Fig. 1: Interrelationships among the domains of health and wellbeing.
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Spiritual wellbeing involves finding and living one’s life purpose and understanding the values and beliefs that guide one’s actions6,7. Spiritual wellbeing has a positive effect on brain health, physical health and mental health8, which in turn have positive effects on social and planetary health.

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Fig. 2: Brain health in the era of the Sustainable Development Goals.
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The figure shows the 17 Sustainable Development Goals (SDGs) set out by the United Nations as a call to action to end poverty and other deprivations, and address climate change, by improving health and education, reducing inequality and driving economic growth. Brain health is central to attaining all of these goals but is particularly important for SDG 3 (health), which itself is central to the other SDGs6.

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Over the past two decades, neuroscience research initiatives such as the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the Human Brain Project, ERA-NET NEURON, the Human Affectome Project9. Specific approaches that could be explored include motivational and spiritual therapies, as well as arts and creative therapies (Fig. 3).

Challenges and solutions

Challenges to implementing the neurological quadrangle can be encountered at the systems, provider, patient and community levels. Table 2 summarizes the challenges at each level, stratified according to the core and pillars of the quadrangle. At the health systems level, potential challenges include inadequate policies and poor planning, infrastructural deficits, suboptimal health system organization, insufficient funding and workforce shortages. Challenges at the health-care provider level can include clinician resistance to change, overwhelming workload and burnout, training and/or skills gaps and poor motivation. Potential challenges at the patient and community levels include low health literacy levels, poor health-seeking behaviour, inadequate health insurance coverage and out-of-pocket payment for health services.

Table 2 Challenges to implementing the neurological quadrangle and proposed solutions
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Potential solutions to the identified challenges are also highlighted in Table 2. They include stronger and better implemented health policies, increased advocacy for neurological health and leveraging of novel technologies and digital solutions. To provide equitable access to diagnostic facilities, drugs and medical devices, efforts should be made to diversify supply chains for pharmaceutical and medical equipment and to formulate intellectual property trade agreements. Personnel shortages could be addressed through training, capacity building and supervised task shifting and sharing. In addition, the brain drain could be slowed down through provision of incentives for workers by policy-makers. Universal health coverage and health equity should be prioritized by every policy-maker to improve access to diagnosis and care.

Efforts aimed at improving neurological services and optimizing brain health must also address the high levels of stigma and discrimination that accompany many neurological disorders. Stigmatization of individuals with a neurological disorder can often be worsened by other forms of discrimination, such as racism. The first global target of the IGAP identifies the need to address stigma and discrimination through intersectoral and interdisciplinary initiatives such as development of national policies, protection of human rights for people living with epilepsy and other neurological disorders and promotion of awareness and advocacy campaigns1.

Advocacy is an important tool in the implementation of the neurological quadrangle and IGAP1 to improve neurological services and optimize brain health. Health diplomacy and advocacy and population-wide educational interventions will be pivotal for the prevention of neurological disorders such as CNS infections, epilepsy, sleep disorders and stroke76,77,84,85. Given the diversity of neurological disorders, disease-specific advocacy is a common approach to ensure adequate representation, even for rare conditions. However, disease-specific advocacy carries the risk of dividing public attention, confusing policy-makers, losing momentum and wasting limited resources. Conversely, stakeholders working synergistically to advance common goals can provide more widespread benefits. Such synergistic efforts should cover all four pillars of the neurological quadrangle and emphasize the importance of patient-oriented care that is predictive, preventive, personalized and participatory86, with sustainability and resilience at the heart of health systems. Crucially, synergies and collaboration for brain health should build on the principles of SDG 17, which emphasizes global partnerships6. This important SDG links directly with SDG 3 (health) and is essential for implementing the intersectoral, multidisease scope of the IGAP1. Important targets of SDG 17 that are relevant for implementation of the IGAP include resource mobilization, LMIC–HIC collaboration and multi-stakeholder engagement to share knowledge, technology and resources; capacity building, especially in the least developed countries and building on existing strengths through leveraging of available resources.

To maximize efforts to improve global brain health, synergy across disciplines, and among policy-makers, patient and caregiver support groups and advocates, is crucial. Across different neurological disorders, patients often experience similar challenges with regard to access to care; timely diagnosis, prognosis and management; discrimination and stigma; socio-economic difficulties and cultural barriers. Furthermore, many individuals have comorbidities of more than one neurological disorder and, though diverse, neurological disorders often share risk factors and underlying pathological processes. For example, stroke and dementia, two leading causes of neurological deaths and DALYs, share both risk factors and protective factors87,88,89,90,91. Similarly, seizures occur commonly in multiple brain disorders, either as a result of brain insults or through shared mechanisms92. These crossovers present unique opportunities for shared preventive strategies and alignment of disease management, and interdisciplinary synergy — for example, digitization of services and national investment in workforce capacity — is required to optimize health system efficiency.

Perhaps most important of all, given the increasing cultural importance being placed on interconnectedness of all life forms on earth (One Health/planetary health; Fig. 1) and a holistic approach to health, exercising an integrated, multisectoral and holistic approach to brain health is becoming increasingly important. This synergistic action must not only leverage new scientific knowledge and technological innovation but also build a broader ecosystem of stakeholders, including the 6Ps14,93 (Fig. 5). Such ecosystems for co-creation, co-implementation and monitoring of pragmatic solutions for brain health are needed at local, national, regional and international levels to deliver transformative impact. These ecosystems can leverage the WHO IGAP and WHO Brain Health52 programmes in synergy with the WHO One Health Initiative, which is an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals and ecosystems.

Fig. 5: A global ecosystem to monitor and reduce the burden of neurological disorders.
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Synergistic action from a broad coalition of multisectoral stakeholders is required to address the global burden of neurological disorders. Key stakeholders include the six Ps: patients, health-care service and product providers, policy-makers, payers, implementation partners and the general population. Implementation partners include neurology organizations and societies, non-governmental agencies and ministries of health, and country ambassadors will act as commissioners. The World Bank and other funders and philanthropists will be approached for funding and support. Adapted versions of the global ecosystem can be adopted as regional and national ecosystems to suit the respective implementation environments14.

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Conclusions

A synergistic and holistic approach to neurological disorders and brain health is central to the attainment of the UN SDG 3 on health and indeed all SDGs6 (Figs. 1 and 2). Insufficient attention to brain health will continue to exert a huge economic and developmental toll on all global populations and economies. As highlighted by this article, neurological disorders must be prioritized at local, regional and global levels by all stakeholders to achieve the greatest benefit for individuals who are directly affected and to lessen the burden on the wider society. Synergistic revolutionary action across the life course is urgently required in the four pillars of the neurological quadrangle — surveillance; primordial, primary and secondary prevention; treatment; and rehabilitation.

The WHO IGAP1 and WHO Brain Health52 initiatives are propelling neurology to the forefront of the global health and development agenda by harmonizing and consolidating global neurology activities and advocacy efforts into a powerful, united force. Sustainable ecosystems are needed in all countries to harness resources and facilitate interdisciplinary collaboration across the four pillars and core of the neurological quadrangle. This new paradigm, promoting neurological and brain health, could improve human health and sustainable development, particularly if combined with the innovative concepts of holistic, spiritual and planetary health. By improving brain health, this revolutionary call to action could foster a profound benefit to human wellbeing, welfare and wealth around the globe.