Global, regional, and national burden of neurological disorders, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

www.thelancet.com/neurology Vol 18 May 2019 459 Articles Lancet Neurol 2019; 18: 459–80 Published Online March 14, 2019 http://dx.doi.org/10.1016/ S1474-4422(18)30499-X See Comment page 418 *Collaborators listed at the end of the Article Correspondence to: Prof Valery L Feigin, National Institute for Stroke and Applied Neurosciences, School of Public Health and Psychosocial Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Northcote, Auckland 0627, New Zealand valery[email protected] or Prof Theo Vos, Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA [email protected] Introduction The UN General Assembly report of December, 2017, underscored that progress in reducing the burden of noncommunicable diseases, including neurologi cal disorders, has been insufficient to meet the UN Sustainable Development Goal targets by 2030.1 Neurological disorders are the leading cause of disability and the second leading cause of death worldwide.2 Thus, strategies and pro grammes that reduce the burden from neurological disorders would potentially help to achieve the UN Sustainable Development Goal targets. Although age-standardised incidence, mortality, and prevalence rates of many neurological disorders declined for many countries from 1990 to 2015, the absolute number of people affected by, dying, or remaining disabled from neurological disorders over the past 25 years Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 GBD 2016 Neurology Collaborators* Summary Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their agestandardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer’s and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer’s disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding Bill & Melinda Gates Foundation. Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Articles 460 www.thelancet.com/neurology Vol 18 May 2019 has been increasing globally.2 Regular assessments of incidence, prevalence, mortality, and disability associated with neurological disorders by cause and over time are important for evidence-based health-care planning, priority setting, and resource allocation. On a global scale, this type of information has facilitated betweencountry and between-region comparisons of the burden from neurological disorders and their trends. The information can also be used for hypothesis generation on causal relationships and effects of sociodemographic and health care factors on the burden from neurological disorders. In 2017, we published aggregated estimates of the burden from neurological disorders2 (as measured by prevalence, mortality, disability-adjusted life-years [DALYs], and years lived with disability [YLDs]), based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2015 data. However, neurological disorders analysed did not include traumatic brain injury (TBI) or spinal cord injury, which are significant sources of global dis ability. Additionally, newly available publications and other data sources were added to the GBD 2016 estimates. In the 2018–19 series of publications in The Lancet Neurology,3–12 we pre sented global, regional, and national estimates of the burden of individual neurological dis orders as meas ured by prevalence, mortality, DALYs, YLDs, years of life lost (YLLs), and, for selected disorders, also incidence, and their trends from 1990 to 2016 accord ing to Socio-demographic Index (SDI), a summary indi cator of income per capita, years of schooling, and total fertility rate. Here, we present updated aggregated estimates (compared with aggregated estimates presented in the GBD 2015 study) of neurological disorders and their trends from 1990 to 2016 by SDI, age, and sex. Methods Overview The Institute for Health Metrics and Evaluation produces annual updates of the GBD study and includes a growing collaboration of scientists. Reported estimates span the period from 1990 to 2016. Annual updates allow incorporation of new data and methodological improvements to ensure that the most up-to-date information is avail able to policy makers to help make resource allocation decisions. In this analysis, we have aggregated results from GBD 2016 for 15 disease and injury outcomes that are generally cared for by neurological services. These include infectious conditions (tetanus, meningitis, and encephalitis), stroke, brain and other CNS cancers, TBI, spinal cord injury, Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type head ache, and a residual category of other less common neurological disorders. Compared to a previous analy sis based on GBD 2015,2 we added non-fatal outcomes of TBI and spinal cord injury. Medication overuse headache is no longer included as a separate cause but quantified as a Research in context Evidence before this study Findings from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2015, showed that neurological disorders are the world’s largest cause of disability. However, some disabling neurological disorders, specifically traumatic brain injury and spinal cord injury, were not included, thus underestimating the global burden of this group of disabilities. No other relevant efforts, beyond GBD, have been made to quantify the global burden of neurological disorders as a whole. The data sources identified after the GBD 2015 study are detailed in the other GBD papers in the series of the neurological disorders overvieved in this paper. Added value of this study This study improves upon GBD 2015 by including four significant considerations. First, compared with a previous analysis based on GBD 2015, we were able to add the non-fatal outcomes of traumatic brain injury and spinal cord injury. Thus, in this analysis, we have aggregated results from GBD 2016 for 15 disease and injury outcomes that are generally cared for by neurological services, such as CNS infectious conditions (tetanus, meningitis, and encephalitis), stroke, brain and other CNS cancers, traumatic brain injury and spinal cord injury, Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category of other less common neurological disorders. Second, we incorporated new data from sources identified after GBD 2015, including peer-reviewed publications, reports from statistical agencies or ministries of health, surveys, and administrative and hospital data. Third, in the individual papers of the burden of neurological disorders analysed, we extended our analysis of GBD results by Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate, with new ways of presenting and visualising changes over time and the relationship with SDI. Fourth, we extended the terminal age group used in our analysis from 80 years and older to 80–84 years, 85–89 year, 90–94 year, and 95 years and older. Implications of all the available evidence Neurological disorders continue to be the leading cause of disability worldwide, and their contribution to the overall burden from all health conditions is increasing. The bulk of the burden from neurological disorders continues to be in low-income and middle-income countries. Ageing of the population, population growth, and ongoing epidemiological transition across all countries require regular updates on the global, regional, and national burden from neurological disorders to allow evidence-based health-care planning and resource allocation for these disorders. Articles www.thelancet.com/neurology Vol 18 May 2019 461 Absolute numbers (thousands) Age-standardised rate (per 100 000 people) 2016 Percentage change, 1990–2016 2016 Percentage change, 1990–2016 Males Females Male-to-female ratio All neurological disorders Deaths 9039 (8772 to 9364) 39% (34 to 44) 144 (140 to 149) –28% (–30 to –26) 160 (155 to 166) 129 (124 to 135) 1·24 (1·20 to 1·29) DALYs 276 143 (246 544 to 307 994) 15% (9 to 21) 3968 (3557 to 4396) –27% (–31 to –24) 4204 (3855 to 4575) 3755 (3272 to 4279) 1·12 (1·05 to 1·20) Tetanus Deaths 37 (22 to 47) –89% (–91 to –86) 1 (0 to 1) –91% (–93 to –88) 1 (0 to 1) 0 (0 to 1) 1·55 (0·85 to 2·15) DALYs 2367 (1446 to 3063) –90% (–93 to –88) 34 (20 to 43) –91% (–93 to –89) 41 (21 to 56) 26 (16 to 35) 1·59 (0·93 to 2·25) Incidence 90 (51 to 121) –89% (–92 to –86) 1 (1 to 2) –91% (–93 to –88) 2 (1 to 2) 1 (1 to 1) 1·72 (0·98 to 2·37) Meningitis Deaths 318 (265 to 409) –21% (–36 to 9) 5 (4 to 6) –36% (–47 to –12) 5 (4 to 7) 4 (3 to 6) 1·25 (0·86 to 1·86) DALYs 21 866 (18 205 to 28 281) –28% (–42 to 3) 306 (254 to 398) –36% (–48 to –10) 328 (261 to 428) 284 (224 to 423) 1·18 (0·79 to 1·66) Incidence 2821 (2464 to 3310) 13% (10 to 16) 39 (35 to 46) –4% (–7 to –1) 42 (36 to 49) 37 (32 to 44) 1·12 (1·10 to 1·14) Encephalitis Deaths 103 (84 to 138) –2% (–36 to 70) 1 (1 to 2) –27% (–51 to 21) 2 (1 to 2) 1 (1 to 2) 1·19 (0·81 to 1·57) DALYs 6704 (5469 to 8574) –15% (–44 to 41) 93 (76 to 118) –32% (–54 to 10) 92 (75 to 124) 93 (74 to 124) 0·99 (0·73 to 1·26) Incidence 6534 (5957 to 7165) 29% (26 to 33) 90 (82 to 98) –5% (–6 to –4) 82 (75 to 90) 99 (90 to 109) 0·83 (0·80 to 0·85) Stroke Deaths 5528 (5335 to 5735) 28% (22 to 33) 87 (83 to 90) –36% (–39 to –34) 103 (99 to 107) 72 (69 to 77) 1·42 (1·35 to 1·50) DALYs 116 445 (111 385 to 121 407) 22% (17 to 27) 1711 (1635 to 1784) –34% (–37 to –32) 2046 (1961 to 2126) 1408 (1320 to 1489) 1·45 (1·39 to 1·52) Incidence 13 677 (12 713 to 14 692) 78% (73 to 83) 203 (189 to 218) –8% (–11 to –6) 231 (215 to 248) 179 (166 to 192) 1·29 (1·27 to 1·31) Alzheimer’s disease and other dementias Deaths 2382 (2060 to 2778) 148% (140 to 157) 41 (35 to 48) 4% (1 to 6) 37 (32 to 44) 43 (37 to 49) 0·88 (0·86 to 0·91) DALYs 28 764 (24 511 to 33 952) 121% (115 to 127) 471 (401 to 556) 2% (0 to 4) 439 (373 to 523) 490 (417 to 576) 0·90 (0·88 to 0·92) Prevalence 43 836 (37 756 to 51 028) 117% (114 to 121) 712 (614 to 828) 2% (1 to 2) 645 (555 to 752) 757 (652 to 879) 0·85 (0·85 to 0·86) Parkinson’s disease Deaths 211 (168 to 265) 161% (152 to 171) 3 (3 to 4) 19% (16 to 23) 5 (4 to 6) 3 (2 to 3) 1·81 (1·74 to 1·89) DALYs 3235 (2564 to 4013) 148% (140 to 156) 51 (41 to 63) 22% (18 to 26) 67 (53 to 83) 39 (31 to 49) 1·70 (1·63 to 1·76) Prevalence 6063 (4971 to 7325) 145% (138 to 152) 94 (77 to 114) 22% (18 to 25) 112 (92 to 135) 80 (65 to 97) 1·40 (1·36 to 1·43) Idiopathic epilepsy Deaths 126 (119 to 136) 9% (–3 to 30) 2 (2 to 2) –24% (–32 to –11) 2 (2 to 2) 1 (1 to 2) 1·50 (1·37 to 1·68) DALYs 13 492 (11 015 to 16 503) 9% (–3 to 24) 183 (149 to 223) –19% (–28 to –9) 201 (167 to 241) 164 (131 to 204) 1·23 (1·16 to 1·31) Prevalence 23 962 (20 402 to 27 737) 48% (34 to 63) 327 (278 to 378) 6% (–4 to 17) 334 (286 to 387) 320 (272 to 372) 1·04 (1·02 to 1·06) Multiple sclerosis Deaths 19 (17 to 21) 61% (19 to 74) 0 (0 to 0) –12% (–35 to –5) 0 (0 to 0) 0 (0 to 0) 0·74 (0·63 to 0·91) DALYs 1151 (969 to 1346) 66% (45 to 75) 16 (13 to 18) –4% (–16 to 1) 12 (10 to 14) 19 (16 to 23) 0·60 (0·54 to 0·67) Prevalence 2221 (2034 to 2437) 88% (85 to 90) 30 (28 to 33) 10% (9 to 12) 19 (18 to 21) 41 (37 to 45) 0·48 (0·46 to 0·49) Migraine DALYs 45 122 (29 046 to 62 827) 51% (50 to 53) 599 (386 to 833) 0% (–1 to 0) 422 (274 to 587) 778 (500 to 1084) 0·54 (0·53 to 0·56) Prevalence 1044 771 (999 535 to 1087 969) 48% (47 to 49) 13 847 (13 255 to 14 418) –2% (–2 to –2) 9356 (8962 to 9753) 18 408 (17 623 to 19 194) 0·51 (0·50 to 0·51) Tension-type headache DALYs 7195 (4615 to 10 500) 53% (47 to 58) 96 (62 to 140) 0% (–3 to 2) 77 (50 to 113) 115 (74 to 167) 0·68 (0·67 to 0·68) Prevalence 1890 670 (1707 786 to 2097 762) 37% (35 to 39) 25 130 (22 741 to 27 895) –7% (–8 to –7) 20 369 (18 312 to 22 765) 29 962 (27 231 to 33 041) 0·68 (0·67 to 0·69) (Table 1 continues on next page) Articles 462 www.thelancet.com/neurology Vol 18 May 2019 consequence of the underlying headache types. For all neurological disorders combined we report here estimates of deaths and DALYs because aggregate incidence and prevalence estimates of combined neuro logical disorders are not useful for policy making. In the methods section of this overview paper, we present a summary of the general methods of the GBD as they apply to neurological disorders. In the ten accompanying disease-specific papers, we have concentrated on methods that are specific to each disorder. Details on the methods of estimates for tetanus, encephalitis, and the residual category of other neurological disorders are provided in the appendix. The guiding principle of GBD is to assess health loss due to mortality and disability comprehensively, defining disability as any departure from full health. In GBD 2016, estimates were made for 195 countries and territories and 579 subnational locations, for 27 years starting from 1990, for 23 age groups, and for both sexes. Deaths were estimated for 264 diseases and injuries, whereas prevalence and incidence were estimated for 328 diseases and injuries. To allow meaningful comparisons between deaths and non-fatal disease outcomes as well as between diseases, data for deaths from and prevalence of neurological disorders are summarised in a single indicator, the DALY. DALYs are the sum of YLLs and YLDs. YLLs are estimated as the product of counts of deaths and a standard ideal remaining life expectancy at the age of death. The standard life expectancy is derived from the lowest observed mortality rates by age in any population in the world larger than 5 million people.13 YLDs are estimated as the product of prevalence of individual consequences of disease (or sequelae) multiplied by their corresponding disability weights, which quantify the relative severity of sequelae as a number between 0 (representing full health) and 1 (representing death). Disability weights have been estimated in nine population surveys and an open-access internet survey in which respondents were asked to choose the healthier option between random pairs of health states that were presented with short descriptions of their main features.14 Mortality estimates All-cause mortality rates are estimated from vital registration data in countries with complete coverage as analysed by demographic growth balance methods comparing successive census population counts.15 For other countries, the probabilities of death before age 5 years and between ages 15 and 60 years are estimated from censuses and surveys asking mothers to provide a history of child ren ever born and those still alive, and surveys asking adults about siblings who are alive or have died. Using model life tables, these probabilities of death are trans formed into age-specific death rates by location, year, and sex. GBD has collated a large database of cause-of-death data from vital registrations and verbal autopsy surveys in which relatives are asked a standard set of questions to ascertain the likely cause of death, Absolute numbers (thousands) Age-standardised rate (per 100 000 people) 2016 Percentage change, 1990–2016 2016 Percentage change, 1990–2016 Males Females Male-to-female ratio (Continued from previous page) Motor neuron diseases Deaths 34 (33 to 35) 94% (80 to 102) 1 (0 to 1) 8% (0 to 12) 1 (1 to 1) 0 (0 to 0) 1·46 (1·36 to 1·54) DALYs 926 (882 to 962) 59% (45 to 72) 13 (13 to 14) –2% (–9 to 3) 16 (15 to 16) 11 (10 to 11) 1·47 (1·36 to 1·54) Prevalence 331 (300 to 367) 67 %(62 to 72) 5 (4 to 5) 5% (3 to 6) 5 (5 to 6) 4 (4 to 5) 1·25 (1·23 to 1·28) Brain and other CNS cancer Deaths 227 (205 to 241) 64% (54 to 82) 3 (3 to 3) –2% (–8 to 8) 4 (3 to 4) 3 (2 to 3) 1·41 (1·21 to 1·65) DALYs 7660 (6923 to 8280) 36% (26 to 55) 105 (95 to 113) –10% (–16 to 3) 122 (106 to 135) 88 (77 to 97) 1·39 (1·18 to 1·64) Prevalence 781 (693 to 818) 97% (84 to 115) 11 (10 to 12) 25% (17 to 34) 12 (10 to 13) 10 (9 to 11) 1·14 (0·98 to 1·31) Traumatic brain injuries DALYs 8000 (5856 to 10 108) 77% (17 to 157) 111 (82 to 141) 9% (8 to 9) 141 (104 to 180) 82 (61 to 101) 1·76 (1·16 to 2·58) Incidence 27 082 (24 302 to 30 299) 47% (44 to 51) 369 (331 to 412) 4% (2 to 5) 471 (427 to 520) 264 (232 to 301) 1·79 (1·70 to 1·88) Spinal cord injuries DALYs 9522 (6700 to 12 449) 40% (36 to 44) 130 (90 to 170) –10% (–13 to –7) 145 (100 to 188) 113 (80 to 146) 1·29 (1·11 to 1·48) Incidence 935 (781 to 1155) 39% (33 to 49) 13 (11 to 16) –4% (–7 to 4) 15 (12 to 18) 11 (9 to 14) 1·37 (1·27 to 1·47) Other neurological disorders Deaths 53 (51 to 55) 66% (51 to 78) 1 (1 to 1) 1% (–5 to 5) 1 (1 to 1) 1 (1 to 1) 1·42 (1·29 to 1·54) DALYs 3695 (3114 to 4353) 54% (39 to 68) 51 (43 to 60) 11% (2 to 20) 55 (47 to 64) 46 (38 to 55) 1·21 (1·13 to 1·31) Numbers in brackets are 95% uncertainty intervals. DALYs for traumatic brain injuries and spinal cord injuries include years lived with disability only (not years of life lost), because International Classification of Disease rules for cause of death reporting require that injury deaths are assigned to causes rather than consequences. We report incidence or prevalence depending on what is the most commonly used or relevant measure of frequency. Prevalence estimates of other neurological disorders and all neurological disorders were not computed because aggregates of prevalence among disparate disease entities are not very informative to policy. DALYS=disability-adjusted life-years. Table 1: Global deaths, DALYs, incidence, and prevalence per 100 000 people and age-standardised rates by neurological disorder category, 1990–2016 Articles www.thelancet.com/neurology Vol 18 May 2019 463 supple mented with police and mortuary data for injury deaths in countries with no other data. Cause-ofdeath informa tion is provided in a large number of different classifica tion systems based on versions of the International Classification of Diseases (ICD) or bespoke classifications in some countries. All data are mapped into the disease and injury categories of GBD. All classification systems contain codes that are less informative than ICD because they do not have a specific diagnosis (eg, unspecified cancer) or refer to codes that cannot be the underlying cause of death (eg, low back pain or senility) or are intermediate causes (eg, heart failure or sepsis). Such deaths are redistributed to more precise underlying causes of death.13 After these redistribu tions and corrections for under-registration, the data are analysed with the Cause of Death Ensemble model (CODEm), a highly systematised tool that runs many different models on the same data and chooses an ensemble of models that best reflects all the available input data. The statistical performance of all models is tested by withholding 30% of the data and checking how well a model covers the data that were held out. To enforce consistency from CODEm, the sum of all-cause specific mortality rates is scaled to that of the all-cause mortality rates in each age, sex, location, and year category. All our estimates of causes of death are categorical: each death is assigned to a single underlying cause. This means that all estimates add to 100%. Non-fatal estimates Non-fatal estimates are based on systematic reviews of published papers and unpublished documents, survey microdata, administrative records of health encounters, registries, and disease surveillance systems. These data sources are catalogued in our Global Health Data Exchange (GHDx), the largest repository of health data globally. We first set a reference case definition or study method, or both, that best quantifies each disease or injury or consequence thereof. If there is evidence of a systematic bias in data that used different case definitions or methods compared to reference data, we adjust those datapoints to reflect what their value would have been if measured as the reference. DisMod-MR 2.1, a Bayesian meta-regression tool, is our main method of analysing non-fatal data. It is designed as a geographical cascade where a first model is run on data from all countries, which produces an initial global fit and estimates coefficients for predictor variables and the adjustments for alternative study characteristics. The global fit adjusted by the values of random effects for each of seven GBD super-regions (appendix), the coefficients on sex, and country predictors, is passed down as data to a model for each super-region together with the input data for that geography. The same steps are repeated going from super-regions to 21 regions and then to 195 countries and, where applicable, a further level down to subnational units. Below the global level, all models are run separately by sex and for six time periods (1990, 1995, For GHDx metadata see http://ghdx.healthdata.org Figure 1: Ranking of age-standardised DALY rates for all neurological disorders by region, 2016 DALY=disability-adjusted life-year. Global East Asia Southeast Asia Oceania Central Asia Central Europe Eastern Europe High-income Asia Pacific Australasia Western Europe Southern Latin America High−income North America Caribbean Andean Latin America Central Latin America Tropical Latin America North Africa and Middle East South Asia Central sub−Saharan Africa Eastern sub−Saharan Africa Southern sub−Saharan Africa Western sub−Saharan Africa Motor neuron diseases Multiple sclerosis Tetanus Other neurological disorders Parkinson's disease Encephalitis Tension-type headache Brain and other CNS cancer Traumatic brain injury Spinal cord injury Epilepsy Meningitis Alzheimer's disease and other dementias Migraine Stroke 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5 10 15 1 Rank See Online for appendix Articles 464 www.thelancet.com/neurology Vol 18 May 2019 2000, 2005, 2010, and 2016). During each analysis, all data for pre valence, incidence, remission (ie, cure rate), and mort ality are forced to be internally consistent. For most diseases, the bulk of data for prevalence or incidence are at the disease level, with even fewer studies providing data on the proportions of cases of disease in each of the sequelae defined for the disease. The proportions in each sequela are pooled using DisMod-MR 2.1 or meta-analysis, or are derived from analyses of patient-level datasets. The multiplication of prevalent cases for each disease sequela and the appropriate disability weight produces YLD estimates that do not yet take into account comorbidity. To correct for comorbidity, these data are used in a simulation to create hypothetical individuals in each age, sex, location, and year combination who have none, one, or multiple sequelae simultaneously. We assume that disability weights are multiplicative rather than additive because this avoids assigning a combined disability weight value in any individual exceeding 1—ie, worse off than a year lost due to death. Risk factors For risks, we use a different, counterfactual approach— ie, answering the question “what would the burden have been if the population had been exposed to a theoretical minimum level of exposure to a risk?” Thus, we need to define what level of exposure to a risk factor leads to the lowest amount of disease. We then analyse data on the prevalence of exposure to a risk and derive relative risks for any risk–outcome pair for which we find sufficient evidence of a causal relationship.16 Prevalence of exposure is estimated in DisMod-MR 2.1 using spatiotemporal Gaussian process regression, or from satellite imagery in the case of ambient air pollution. Relative risk data are pooled using meta-analysis of cohort, case-control, and intervention studies. From the prevalence and relative risk results, population attributable fractions are estimated relative to the theoretical minimum risk exposure level (TMREL). Criteria for inclusion of risks into GBD were the availability of sufficient evidence for a causal relationship between a risk and one or more disease or injury outcomes; evidence to support generalisability of an effect size beyond the populations included in epidemiological studies; availability of sufficient data and methods to enable estimation of exposure levels by country; and the likely importance of a risk factor to disease burden or policy considerations.17 Uncertainty intervals (UIs) Uncertainty is propagated throughout all these calculations by creating 1000 values for each prevalence, death, YLL, YLD, or DALY estimate and performing aggregations across causes and locations at the level of each of the 1000 values for all intermediate steps in the calculation. The lower and upper bounds of the 95% UI are the 25th and 975th values of the ordered 1000 values. Significance of differences was established if 975 or more of the ordered 1000 values of difference were on either side of zero. SDI GBD uses a composite indicator of sociodemographic development, SDI, which reflects the geometric mean of normalised values of a location’s income per capita, the average years of schooling in the population aged 15 years and older, and the total fertility rate. Coun tries and territories are grouped into quintiles of high, high-middle, middle, low-middle, and low SDI based on their 2016 values.13 Figure 2: Global DALYs for neurological disorders by sex and age, 2016 Early neonatal is 0–7 days; late neonatal is 7–28 days; and post-neonatal is 28 days to 1 year. (A) Females. (B) Males. DALY=disability-adjusted life-year. Early neonata l Late neonata l Post neonatal 1–4 5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 85–89 90–94 ≥95 0 5000 10 000 15 000 DALYs (thousands) Age group (years) A 0 5000 10 000 15 000 DALYs (thousands) B Tetanus Meningitis Encephalitis Stroke Alzheimer’s disease and other dementias Parkinson’s disease Idiopathic epilepsy Multiple sclerosis Motor neuron diseases Migraine Tension-type headache Traumatic brain injury Spinal cord injury Brain and other CNS cancer Other neurological disorders Articles www.thelancet.com/neurology Vol 18 May 2019 465 Role of the funding source The funder of the study had no role in study design, data collection, data analysis, data interpretation, or the writing of the report. All authors had full access to the data in the study and had final responsibility for the decision to submit for publication. Results In 2016, the neurological disorders included in this analysis were responsible for 276 million (95% UI 247–308) DALYs, comprising 11·6% (10·7–12·4) of global DALYs for all diseases. Combined, these disorders were the underlying cause in 9·0 million (8·8–9·4) deaths or 16·5% (16·1–17·0) of total global deaths in 2016. Incidence and prevalence estimates for each neurological disorder can be found in the GBD online results tool. Results and findings mentioned can also be viewed interactively through an online data visualisation tool. Neurological disorders were the leading cause group of global DALYs in 2016, followed by cardiovascular diseases (excluding stroke). In terms of deaths, these combined neurological disorders ranked second after cardiovascular diseases. Since 1990, the number of deaths from neurological disorders increased by 39% (34–44) and DALYs for neurological disorders increased by 15% (9–21). However, age-standardised mortality rates decreased by 28% (26–30) over the same time, indicating that popula tion increase and ageing are driving global numbers higher, even though the global population is exposed to a lower risk of death from these causes, as indicated by the lower age-standardised rates. Sim ilarly, the age-standardised DALY rates decreased by 27% (24–31) between 1990 and 2016. The only neuro logical disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. Stroke was the largest contributor to global neurological DALYs, responsible for 42·2% (95% UI 38·6–46·1) of these DALYs in 2016 (table 1). Migraine was the second largest contributor (16·3% [11·7–20·8]), followed by Alzheimer’s and other dementias (10·4% [9·0–12·1]) and meningitis (7·9% [6·6–10·4]). Stroke ranked first among neurological disorders in terms of age-standardised DALY rates in 19 of 21 world regions (figure 1). In Australasia and western Europe, migraine ranked first. Migraine and Alzheimer’s disease and other dementias were ranked among the top four contributing neurological conditions in all 21 GBD world regions. Large variations in ranking were found for meningitis (ranked second in central, eastern, and western sub-Saharan Africa and 14th in high-income Asia Pacific), epilepsy (ranked second in southern sub-Saharan Africa and third in central Asia and eighth in eastern Europe), and encephalitis (ranked fifth in south Asia and 14th in Australasia, western Europe, and high-income North America). Other high rankings of note are for spinal cord injury (ranked fourth in all five high-income regions), TBI (ranked fourth in central and eastern Europe), and tetanus (ranked sixth in eastern subSaharan Africa; figure 1). Across the aggregate of 15 neurological disorder categories analysed, age-standardised DALY rates were significantly higher in males than in females (male-tofemale ratio 1·12 [95% UI 1·05–1·20]). When examining individual disorders, a significantly higher burden (as measured by age-standardised DALY rates) in males than females was observed for TBI, Parkinson’s disease, tetanus, motor neuron diseases, and stroke, with male-tofemale ratios of at least 1·5. By contrast, migraine, Figure 3: Global YLLs and YLDs for neurological disorders by age, 2016 YLLs (A) and YLDs (B). Early neonatal is 0–7 days; late neonatal is 7–28 days; post-neonatal is 28 days to 1 year. YLDs=years lived with disability. YLLs=years of life lost. Early neonata l Late neonata l Post neonatal 1–4 5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 85–89 90–94 ≥95 0 5000 10 000 15 000 YLDs (thousands) Age group (years) B 0 5000 10 000 20 000 15 000 YLLs (thousands) A Tetanus Meningitis Encephalitis Stroke Alzheimer’s disease and other dementias Parkinson’s disease Idiopathic epilepsy Multiple sclerosis Motor neuron diseases Brain and other CNS cancer Other neurological disorders Migraine Tension-type headache Traumatic brain injury Spinal chord injury For the online results tool see http://ghdx.healthdata.org/gbdresults-tool For the online data visualisation tool see https://vizhub.healthdata.org/ gbd-compare Articles 466 www.thelancet.com/neurology Vol 18 May 2019 Absolute numbers of DALYs (thousands) Age-standardised DALY rates (per 100 000 people) 1990 2016 Percentage change, 1990–2016 1990 2016 Percentage change, 1990–2016 Global 240 379 (219 338 to 262 279) 276 143 (246 544 to 307 994) 15% (9 to 21) 5467 (5024 to 5913) 3968 (3557 to 4396) –27% (–31 to –24) High-income North America 8455 (7193 to 9751) 11 780 (10 040 to 13 527) 39% (37 to 42) 2867 (2446 to 3305) 2629 (2208 to 3056) –8% (–10 to –7) Canada 794 (667 to 932) 1137 (950 to 1331) 43% (37 to 50) 2807 (2366 to 3271) 2433 (1998 to 2884) –13% (–18 to –9) Greenland 2 (2 to 2) 2 (1 to 2) –12% (–24 to 1) 6956 (6236 to 7848) 4262 (3552 to 4953) –39% (–47 to –30) USA 7658 (6530 to 8823) 10 640 (9085 to 12 209) 39% (36 to 42) 2872 (2451 to 3310) 2652 (2232 to 3083) –8% (–10 to –6) Australasia 624 (529 to 723) 860 (725 to 1007) 38% (32 to 44) 3047 (2602 to 3498) 2444 (2020 to 2902) –20% (–24 to –15) Australia 516 (437 to 598) 722 (608 to 846) 40% (33 to 47) 3016 (2573 to 3482) 2430 (2002 to 2905) –20% (–24 to –15) New Zealand 108 (92 to 123) 138 (116 to 162) 28% (20 to 36) 3201 (2763 to 3650) 2518 (2082 to 2988) –21% (–27 to –16) High-income Asia-Pacific 6136 (5368 to 6922) 7635 (6626 to 8723) 24% (18 to 31) 3643 (3210 to 4091) 2511 (2100 to 2959) –31% (–35 to –27) Brunei 6 (5 to 7) 11 (9 to 13) 71% (53 to 91) 4183 (3693 to 4689) 3192 (2726 to 3738) –24% (–31 to –16) Japan 4336 (3781 to 4904) 5715 (4977 to 6480) 32% (27 to 37) 3202 (2786 to 3626) 2410 (2012 to 2827) –25% (–28 to –22) Singapore 73 (63 to 86) 102 (83 to 122) 39% (26 to 55) 3436 (2998 to 3912) 2225 (1809 to 2670) –35% (–43 to –28) South Korea 1730 (1506 to 1959) 1807 (1453 to 2157) 4% (–12 to 22) 5929 (5300 to 6575) 2912 (2351 to 3455) –51% (–59 to –43) Western Europe 16 002 (13 971 to 18 071) 16 727 (14 215 to 19 172) 4% (1 to 8) 3489 (3004 to 3973) 2686 (2219 to 3174) –23% (–27 to –20) Andorra 2 (1 to 2) 3 (3 to 4) 74% (53 to 98) 3008 (2437 to 3591) 2686 (2180 to 3231) –11% (–21 to 0) Austria 342 (299 to 389) 318 (264 to 375) –7% (–13 to –1) 3651 (3139 to 4178) 2632 (2137 to 3163) –28% (–33 to –23) Belgium 430 (375 to 489) 454 (385 to 530) 6% (–2 to 12) 3558 (3073 to 4108) 2823 (2329 to 3363) –21% (–27 to –15) Cyprus 24 (21 to 27) 30 (25 to 36) 28% (19 to 37) 3663 (3169 to 4215) 2756 (2247 to 3268) –25% (–31 to –19) Denmark 220 (192 to 250) 206 (174 to 240) –6% (–13 to 1) 3460 (2967 to 3962) 2693 (2232 to 3200) –22% (–28 to –16) Finland 227 (199 to 256) 245 (210 to 283) 8% (2 to 14) 3932 (3440 to 4459) 2995 (2498 to 3538) –24% (–29 to –19) France 2070 (1763 to 2376) 2349 (1985 to 2737) 13% (7 to 20) 3134 (2644 to 3638) 2576 (2101 to 3096) –18% (–24 to –11) Germany 3479 (3047 to 3951) 3290 (2798 to 3810) –5% (–12 to 2) 3498 (3020 to 4025) 2645 (2172 to 3159) –24% (–31 to –17) Greece 488 (434 to 545) 530 (464 to 601) 9% (3 to 15) 4000 (3515 to 4505) 3002 (2535 to 3501) –25% (–30 to –21) Iceland 8 (7 to 10) 11 (9 to 13) 34% (27 to 42) 3229 (2748 to 3740) 2793 (2304 to 3319) –14% (–19 to –8) Ireland 126 (108 to 144) 145 (120 to 173) 15% (6 to 24) 3578 (3078 to 4082) 2747 (2258 to 3298) –23% (–30 to –17) Israel 137 (116 to 158) 223 (183 to 268) 62% (47 to 78) 3432 (2939 to 3948) 2632 (2140 to 3188) –23% (–31 to –16) Italy 2448 (2118 to 2794) 2684 (2279 to 3088) 10% (4 to 17) 3533 (3010 to 4084) 2729 (2228 to 3269) –23% (–28 to –18) Luxembourg 18 (16 to 20) 20 (16 to 23) 8% (–1 to 17) 4068 (3555 to 4624) 2704 (2221 to 3233) –34% (–39 to –28) Malta 12 (11 to 14) 15 (13 to 18) 22% (11 to 34) 3601 (3091 to 4140) 2700 (2187 to 3228) –25% (–32 to –18) Netherlands 539 (463 to 624) 614 (517 to 713) 14% (7 to 21) 3232 (2770 to 3743) 2680 (2198 to 3191) –17% (–23 to –11) Norway 181 (159 to 204) 181 (153 to 210) 0% (–7 to 8) 3380 (2926 to 3859) 2653 (2200 to 3134) –22% (–27 to –15) Portugal 604 (550 to 663) 487 (424 to 555) –19% (–24 to –15) 5166 (4651 to 5701) 2964 (2488 to 3476) –43% (–47 to –38) Spain 1533 (1331 to 1744) 1791 (1511 to 2069) 17% (11 to 22) 3482 (2995 to 3982) 2596 (2118 to 3110) –26% (–30 to –21) Sweden 340 (297 to 385) 361 (305 to 415) 6% (–1 to 13) 2983 (2540 to 3451) 2531 (2074 to 2974) –15% (–21 to –10) Switzerland 266 (228 to 307) 292 (239 to 350) 10% (–1 to 23) 3244 (2744 to 3785) 2474 (1979 to 3010) –24% (–31 to –16) UK 2503 (2210 to 2814) 2467 (2113 to 2832) –2% (–5 to 1) 3538 (3087 to 4032) 2771 (2303 to 3255) –22% (–25 to –19) Southern Latin America 1702 (1509 to 1908) 1849 (1557 to 2150) 9% (1 to 16) 3907 (3484 to 4353) 2680 (2256 to 3120) –31% (–36 to –27) Argentina 1176 (1047 to 1313) 1214 (1033 to 1411) 3% (–4 to 11) 3960 (3535 to 4408) 2696 (2288 to 3135) –32% (–37 to –27) Chile 396 (344 to 458) 511 (414 to 616) 29% (13 to 47) 3757 (3330 to 4254) 2592 (2101 to 3120) –31% (–40 to –21) Uruguay 130 (117 to 144) 124 (108 to 141) –4% (–10 to 2) 4006 (3593 to 4464) 2927 (2500 to 3380) –27% (–32 to –22) Eastern Europe 13 148 (11 851 to 14 406) 12 781 (10 708 to 15 168) –3% (–16 to 12) 5762 (5216 to 6301) 4723 (3975 to 5551) –18% (–28 to –6) Belarus 522 (467 to 579) 495 (420 to 572) –5% (–15 to 5) 4969 (4467 to 5488) 4146 (3525 to 4771) –17% (–25 to –9) Estonia 92 (83 to 101) 56 (47 to 65) –39% (–46 to –33) 5442 (4910 to 5963) 3114 (2604 to 3640) –43% (–48 to –37) Latvia 172 (156 to 190) 123 (106 to 138) –29% (–34 to –22) 5881 (5336 to 6470) 4125 (3553 to 4712) –30% (–36 to –24) Lithuania 155 (137 to 174) 149 (132 to 167) –4% (–9 to 2) 4167 (3678 to 4658) 3633 (3156 to 4110) –13% (–17 to –8) Moldova 226 (203 to 250) 201 (176 to 230) –11% (–19 to –2) 5875 (5317 to 6431) 4492 (3944 to 5117) –24% (–31 to –17) Russia 8854 (7878 to 9776) 9137 (7442 to 11 332) 3% (–15 to 26) 5990 (5357 to 6584) 4972 (4087 to 6090) –17% (–30 to 0) Ukraine 3126 (2835 to 3440) 2622 (2169 to 3132) –16% (–27 to –3) 5460 (4916 to 6030) 4326 (3599 to 5155) –21% (–31 to –9) (Table 2 continues on next page) Articles www.thelancet.com/neurology Vol 18 May 2019 467 Absolute numbers of DALYs (thousands) Age-standardised DALY rates (per 100 000 people) 1990 2016 Percentage change, 1990–2016 1990 2016 Percentage change, 1990–2016 (Continued from previous page) Central Europe 6289 (5663 to 6896) 5701 (5055 to 6380) –9% (–13 to –6) 5172 (4678 to 5662) 3758 (3278 to 4241) –27% (–31 to –24) Albania 116 (101 to 132) 140 (122 to 159) 21% (7 to 35) 4838 (4353 to 5362) 4437 (3879 to 5028) –8% (–17 to 1) Bosnia and Herzegovina 191 (168 to 216) 205 (179 to 235) 7% (–5 to 21) 5193 (4626 to 5763) 4137 (3593 to 4794) –20% (–29 to –11) Bulgaria 615 (563 to 669) 508 (441 to 572) –17% (–26 to –8) 6120 (5564 to 6659) 4637 (3997 to 5233) –24% (–31 to –17) Croatia 260 (233 to 290) 225 (198 to 256) –13% (–21 to –5) 5030 (4485 to 5606) 3662 (3173 to 4202) –27% (–34 to –20) Czech Republic 576 (520 to 635) 415 (355 to 479) –28% (–33 to –23) 5201 (4686 to 5744) 3112 (2635 to 3641) –40% (–45 to –35) Hungary 639 (579 to 703) 467 (400 to 531) –27% (–33 to –21) 5447 (4924 to 6007) 3496 (2976 to 4014) –36% (–42 to –30) Macedonia 102 (91 to 114) 124 (111 to 138) 21% (13 to 30) 6304 (5682 to 7012) 5154 (4606 to 5763) –18% (–24 to –12) Montenegro 30 (27 to 33) 36 (32 to 41) 21% (9 to 33) 5433 (4878 to 6006) 4772 (4218 to 5331) –12% (–20 to –4) Poland 1589 (1407 to 1770) 1555 (1335 to 1778) –2% (–9 to 5) 4390 (3910 to 4872) 3246 (2782 to 3753) –26% (–31 to –21) Romania 1352 (1226 to 1487) 1231 (1096 to 1376) –9% (–16 to –2) 5814 (5265 to 6371) 4492 (3961 to 5057) –23% (–28 to –17) Serbia 498 (440 to 559) 498 (438 to 561) 0% (–8 to 8) 5402 (4811 to 6057) 4260 (3697 to 4830) –21% (–27 to –15) Slovakia 225 (199 to 253) 219 (185 to 253) –3% (–11 to 7) 4579 (4069 to 5106) 3420 (2907 to 3952) –25% (–32 to –18) Slovenia 88 (77 to 101) 79 (67 to 92) –11% (–20 to –2) 4414 (3855 to 4983) 2909 (2431 to 3444) –34% (–41 to –27) Central Asia 2740 (2477 to 3023) 3305 (2919 to 3726) 21% (15 to 27) 5522 (5055 to 6014) 4661 (4197 to 5173) –16% (–19 to –12) Armenia 117 (102 to 135) 105 (89 to 122) –11% (–18 to –3) 4325 (3839 to 4844) 3184 (2714 to 3713) –26% (–32 to –20) Azerbaijan 247 (216 to 280) 359 (302 to 420) 45% (27 to 63) 4924 (4415 to 5463) 4248 (3627 to 4917) –14% (–24 to –4) Georgia 306 (276 to 338) 228 (199 to 261) –25% (–34 to –16) 5721 (5177 to 6290) 4543 (3947 to 5206) –21% (–29 to –11) Kazakhstan 703 (625 to 791) 694 (589 to 809) –1% (–12 to 12) 5586 (5029 to 6189) 4614 (3941 to 5317) –17% (–26 to –7) Kyrgyzstan 198 (179 to 218) 207 (181 to 235) 5% (–4 to 14) 6426 (5918 to 6973) 4867 (4364 to 5438) –24% (–30 to –18) Mongolia 95 (76 to 116) 141 (123 to 162) 50% (21 to 85) 5749 (5075 to 6485) 6460 (5729 to 7287) 13% (–2 to 29) Tajikistan 213 (185 to 242) 279 (238 to 326) 31% (12 to 53) 5819 (5211 to 6476) 5037 (4427 to 5718) –13% (–23 to –2) Turkmenistan 137 (122 to 153) 206 (181 to 232) 50% (37 to 65) 5646 (5164 to 6181) 5085 (4582 to 5587) –10% (–16 to –3) Uzbekistan 722 (637 to 820) 1083 (922 to 1262) 50% (34 to 67) 5300 (4761 to 5896) 4631 (4027 to 5309) –13% (–21 to –4) Central Latin America 4147 (3576 to 4743) 5654 (4688 to 6652) 36% (29 to 43) 3410 (3016 to 3836) 2631 (2241 to 3048) –23% (–26 to –19) Colombia 894 (758 to 1053) 1078 (875 to 1309) 21% (6 to 38) 3692 (3246 to 4213) 2542 (2119 to 3035) –31% (–38 to –23) Costa Rica 62 (51 to 75) 107 (87 to 130) 72% (53 to 92) 2799 (2395 to 3241) 2336 (1937 to 2803) –17% (–25 to –8) El Salvador 161 (138 to 185) 140 (114 to 168) –13% (–23 to –1) 4033 (3536 to 4548) 2538 (2106 to 3000) –37% (–44 to –30) Guatemala 220 (188 to 255) 346 (280 to 419) 58% (35 to 80) 3314 (2843 to 3777) 2823 (2315 to 3365) –15% (–27 to –2) Honduras 200 (173 to 228) 224 (185 to 269) 13% (–5 to 36) 4829 (4234 to 5470) 3461 (2887 to 4126) –28% (–39 to –14) Mexico 1979 (1695 to 2284) 2800 (2332 to 3313) 41% (35 to 48) 3158 (2755 to 3576) 2562 (2173 to 2977) –19% (–22 to –16) Nicaragua 101 (85 to 120) 128 (103 to 155) 27% (10 to 47) 3500 (3026 to 3996) 2644 (2195 to 3120) –24% (–33 to –15) Panama 61 (53 to 71) 94 (78 to 113) 55% (38 to 74) 3526 (3122 to 3997) 2681 (2256 to 3161) –24% (–32 to –16) Venezuela 467 (394 to 554) 732 (592 to 885) 57% (35 to 81) 3623 (3180 to 4140) 2837 (2350 to 3390) –22% (–31 to –11) Andean Latin America 1114 (981 to 1258) 1248 (1037 to 1496) 12% (1 to 25) 3715 (3321 to 4148) 2457 (2073 to 2913) –34% (–40 to –28) Bolivia 272 (234 to 310) 272 (225 to 322) 0% (–16 to 17) 4942 (4339 to 5634) 3022 (2517 to 3552) –39% (–47 to –30) Ecuador 267 (229 to 312) 346 (282 to 416) 29% (13 to 49) 3529 (3096 to 4029) 2467 (2061 to 2928) –30% (–38 to –21) Peru 575 (493 to 657) 630 (509 to 778) 10% (–5 to 28) 3411 (2964 to 3835) 2271 (1868 to 2742) –33% (–41 to –24) Caribbean 1576 (1383 to 1786) 1544 (1346 to 1784) –2% (–14 to 9) 5057 (4518 to 5636) 3539 (3108 to 4056) –30% (–37 to –23) Antigua and Barbuda 2 (2 to 2) 3 (2 to 3) 16% (3 to 30) 4249 (3780 to 4758) 2987 (2538 to 3492) –30% (–37 to –22) The Bahamas 7 (6 to 8) 12 (10 to 14) 68% (51 to 85) 3909 (3470 to 4375) 3142 (2683 to 3604) –20% (–27 to –12) Barbados 10 (8 to 11) 10 (9 to 12) 6% (–2 to 16) 3853 (3421 to 4321) 2963 (2555 to 3428) –23% (–29 to –16) Belize 5 (4 to 6) 8 (7 to 9) 63% (43 to 85) 3606 (3206 to 4065) 3253 (2830 to 3719) –10% (–18 to –1) Bermuda 2 (1 to 2) 2 (1 to 2) 2% (–9 to 14) 3980 (3514 to 4491) 2492 (2081 to 2945) –37% (–44 to –30) Cuba 341 (301 to 385) 395 (342 to 449) 16% (8 to 25) 3542 (3159 to 3965) 2795 (2394 to 3202) –21% (–27 to –15) Dominica 2 (2 to 2) 2 (2 to 3) 15% (3 to 30) 3673 (3258 to 4145) 3155 (2712 to 3645) –14% (–22 to –4) Dominican Republic 215 (188 to 246) 267 (222 to 313) 24% (8 to 40) 4168 (3716 to 4650) 3049 (2590 to 3540) –27% (–35 to –19) Grenada 4 (3 to 4) 4 (3 to 4) –4% (–15 to 9) 4892 (4404 to 5433) 3881 (3384 to 4413) –21% (–30 to –11) Guyana 33 (30 to 36) 29 (25 to 32) –13% (–23 to –3) 7493 (6942 to 8090) 4876 (4350 to 5450) –35% (–41 to –28) (Table 2 continues on next page) Articles 474 www.thelancet.com/neurology Vol 18 May 2019 Khanh Bao Tran, Thomas Clement Truelsen, Afewerki Gebremeskel Tsadik, Lorainne Tudor Car, Kingsley Nnanna Ukwaja, Irfan Ullah, Muhammad Shariq Usman, Olalekan A Uthman, Pascual R Valdez, Tommi Juhani Vasankari, Rajagopalan Vasanthan, Yousef Veisani, Narayanaswamy Venketasubramanian, Francesco S Violante, Vasily Vlassov, Kia Vosoughi, Giang Thu Vu, Isidora S Vujcic, Fasil Shiferaw Wagnew, Yasir Waheed, Yuan-Pang Wang, Elisabete Weiderpass, Jordan Weiss, Harvey A Whiteford, Tissa Wijeratne, Andrea Sylvia Winkler, Charles Shey Wiysonge, Charles D A Wolfe, Gelin Xu, Ali Yadollahpour, Tomohide Yamada, Yuichiro Yano, Mehdi Yaseri, Hiroshi Yatsuya, Ebrahim M Yimer, Paul Yip, Engida Yisma, Naohiro Yonemoto, Mahmoud Yousefifard, Chuanhua Yu, Zoubida Zaidi, Sojib Bin Zaman, Mohammad Zamani, Hamed Zandian, Zohreh Zare, Yunquan Zhang, Sanjay Zodpey, Mohsen Naghavi, Christopher J L Murray, and Theo Vos. Affiliations National Institute for Stroke and Applied Neurosciences (Prof V L Feigin PhD, A Theadom PhD), School of Public Health (R V Krishnamurthi PhD), National Institute for Stroke and Applied Neurosciences (B J Te Ao PhD), Auckland University of Technology, Auckland, New Zealand; Institute for Health Metrics and Evaluation (Prof V L Feigin PhD, E Nichols BA, T Alam MPH, M S Bannick BS, C Fitzmaurice MD, S L James MD, C O Johnson PhD, N J Kassebaum MD, W C Mountjoy-Venning BA, M Nguyen BS, G A Roth MD, Prof S Vollset DrPH, S D Dharmaratne MD, Prof S I Hay FMedSci, I A Khalil MD, Prof A H Mokdad PhD, M R Nixon PhD, N Reinig BS, N L S Roberts BS, M Smith MPA, Prof H A Whiteford PhD, Prof M Naghavi MD, Prof C J L Murray DPhil, Prof T Vos PhD), Department of Neurology (Prof R G Ellenbogen MD, J R Zunt MD, R Kalani MD), Division of Cardiology, Department of Medicine (G A Roth MD), Division of Hematology (C Fitzmaurice MD), Department of Health Metrics Sciences (Prof S Vollset DrPH, Prof S I Hay FMedSci, I A Khalil MD, Prof A H Mokdad PhD, Prof M Naghavi MD, Prof C J L Murray DPhil, Prof T Vos PhD), Division of Plastic Surgery (C S Crowe MD, B B Massenburg MD), Department of Surgery (S D Morrison MD), University of Washington, Seattle, WA, USA (Prof E Oren PhD); Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy (E Beghi MD, G Giussani PhD); Research, Evidence and Policy Department, Meningitis Research Foundation, Bristol, UK (N Blake MSc, L Glennie MSc, C Wright MSc); Department of Veterans Affairs Multiple Sclerosis Center of Excellence, Baltimore, MD, USA (W J Culpepper PhD); Department of Neurology, School of Medicine (W J Culpepper PhD), School of Medicine (M T Wallin MD), University of Maryland, Baltimore, MD, USA; University of Rochester, Rochester, NY, USA (E Dorsey MD); Centre for Research in Epidemiology and Population Health, National Institute of Health and Medical Research, Paris, France (A Elbaz MD); Department of Surgery (Prof R G Ellenbogen MD), Department of Anesthesiology & Pain Medicine (N J Kassebaum MD), Seattle Children’s Hospital, Seattle, WA, USA; James Cancer Hospital (J L Fisher PhD), Department of Pediatrics (W D Lo MD), Ohio State University, Columbus, OH, USA; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M Piccininni MSc), Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology (M Piccininni MSc), University of Bari Aldo Moro, Bari, Italy (Prof G Logroscino PhD); Department of Clinical Research in Neurology, Fondazione Cardinale Giovanni Panico Hospital, Tricase, Italy (Prof G Logroscino PhD); Institute of Neurological Epidemiology and Tropical Neurology, University of Limoges, Limoges, France (B Marin PhD); Centre of Cardiovascular Research and Education in Therapeutics (R Ofori-Asenso MSc), School of Public Health and Preventive Medicine (Prof Y Guo PhD, S Li PhD), Monash University, Melbourne, VIC, Australia (Prof A G Thrift PhD); Independent Consultant, Accra, Ghana (R Ofori-Asenso MSc); Neurosurgery, University of Washington Medical Center, Seattle, WA, USA (A P Patel MD); Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway (Prof T J Steiner PhD, Prof L J Stovner PhD); Division of Brain Sciences (Prof T J Steiner PhD, Prof R A Shakir MD), Department of Primary Care and Public Health (M Car PhD, Prof A Majeed MD, Prof S Rawaf PhD), WHO Collaborating Centre for Public Health Education and Training (D L Rawaf MD), Imperial College London, London, UK; Neuro Centre, St. Olavs Hospital, Trondheim, Norway (Prof L J Stovner PhD); School of Health Sciences (Prof C E I Szoeke PhD, A Meretoja MD, R Sahathevan PhD), Department of Paediatrics (M T Mackay PhD), Department of Medicine (Prof T Wijeratne MD), University of Melbourne, Melbourne, VIC, Australia; The Brain Institute (Prof C E I Szoeke PhD), Mary MacKillop Institute for Health Research (Prof E Cerin PhD), Australian Catholic University, Melbourne, VIC, Australia; Department of Neurology, George Washington University, Washington, DC, USA (M T Wallin MD); Non-communicable Diseases Research Center (N Abbasi MD, F Farzadfar MD, S N Irvani MD, M Shams-Beyranvand MSc, B Mohajer MD, F Mohebi MD), Endocrinology and Metabolism Research Center (M Afarideh MD, Prof A Esteghamati MD, S Esteghamati MD, M Ganji MD), Multiple Sclerosis Research Center (S Eskandarieh PhD, B Mohajer MD, Prof M Sahraian MD), Department of Pharmacology (Arv Haj-Mirzaian MD, Ary Haj-Mirzaian MD), Department of Epidemiology and Biostatistics (Prof S Hosseini PhD, M Mansournia PhD, M Yaseri PhD), Hematologic Malignancies Research Center (A Kasaeian PhD), Knowledge Utilization Research Center (KURC) (Prof R Majdzadeh PhD), Digestive Diseases Research Institute (Prof R Malekzadeh MD, H Poustchi PhD, G Roshandel PhD, S G Sepanlou MD), Iran National Institute of Health Research (F Mohebi MD), Department of Health Management and Economics (S Mousavi PhD), Sina Trauma and Surgery Research Center (Prof V Rahimi-Movaghar MD, Prof P Salamati MD, M Sharif-Alhoseini PhD), Cancer Biology Research Center (R Shirkoohi PhD), Department of Anatomy (S Sobhani MD), Hematology-Oncology and Stem Cell Transplantation Research Center (A Kasaeian PhD), Community-Based Participatory-Research Center (CBPR) (Prof R Majdzadeh PhD), Cancer Research Center (R Shirkoohi PhD), Tehran University of Medical Sciences, Tehran, Iran; Montreal Neuroimaging Center (N Abbasi MD), School of Physical and Occupational Therapy (K K V Mate MSc), McGill University, Montreal, QC, Canada; Department of Neurology, Cairo University, Cairo, Egypt (Prof F Abd-Allah MD, Prof A Abdelalim MD, M I Hegazy PhD); Department of Epidemiology, Arak University of Medical Sciences, Arak, Iran (I Abdollahpour PhD); Multiple Sclerosis Research Center, Tehran, Iran (I Abdollahpour PhD); Department of Cardiology, Dupuytren University Hospital, Limoges, France (Prof V Aboyans MD); Institute of Epidemiology, University of Limoges, Limoges, France (Prof V Aboyans MD); Clinical Pharmacy Unit (H N Abraha MSc, T D Kassa MSc, Y L Nirayo MSc), School of Public Health (A B Belachew MSc), School of Pharmacy (A K Gebre MSc, T G Gebremichael MSc, A G Tsadik MSc, E M Yimer MSc), Department of Biostatistics (K Gezae MSc), Anatomy Unit (T B Hagos MSc), Department of Nutrition and Dietetics (A Kahsay MPH, M G Degefa MSc), School of Medicine (D T Mengistu MSc), Mekelle University, Mekelle, Ethiopia (H G Meles MPH); Department of Preventive Medicine, Dongguk University, Gyeongju, South Korea (D Acharya MPH); Department of Community Medicine, Kathmandu University, Devdaha, Nepal (D Acharya MPH); Department of Global Health (A A Adamu MSc, Prof C S Wiysonge MD), Faculty of Medicine & Health Sciences (Prof P S Nyasulu PhD), Department of Psychiatry (Prof S Seedat PhD), Stellenbosch University, Cape Town, South Africa; Cochrane South Africa (A A Adamu MSc), South African Medical Research Council, Cape Town, South Africa (Prof D J Stein MD); Department of Medicine, University College Hospital, Ibadan, Ibadan, Nigeria (O M Adebayo MD); College of Medicine (A M Adeoye MD), Institute for Advanced Medical Research and Training (R O Akinyemi PhD, Prof M O Owolabi DrM), University of Ibadan, Ibadan, Nigeria; Community Cardiovascular Research Unit, Elyon Heart Rehabilitation Center, Ibadan, Nigeria (A M Adeoye MD); Sport Science Department, University of Extremadura, Badajoz, Spain (J C Adsuar PhD); Indian Institute of Public Health (Prof S Zodpey PhD), Public Health Foundation of India, Gurugram, India (S Agrawal PhD, A Awasthi PhD); Vital Strategies, Gurugram, India (S Agrawal PhD); Department of Anesthesiology (A Ahmadi PhD), Department of Traditional and Complementary Medicine (M Farzaei PhD), Faculty of Nutrition and Food Sciences (F Heydarpour PhD), Department of Psychiatry (Prof H Khazaie MD), Research Center for Environmental Determinants of Health (M Moradinazar PhD), Department of Operating Room, School Articles www.thelancet.com/neurology Vol 18 May 2019 475 of Paramedical (M Naderi MSc), Department of Epidemiology & Biostatistics (Prof F Najafi PhD, Y Salimi PhD), Department of Health Education & Promotion (F Rajati PhD), Faculty of Public Health (R Safari-Faramani PhD), Radiology and Nuclear Medicine (S Salehi Zahabi PhD), Imam Ali Cardiovascular Research Center (S Siabani PhD), Environmental Determinants of Health Research Center (M Soofi PhD), Pharmaceutical Sciences Research Center (M Farzaei PhD), Kermanshah University of Medical Sciences, Kermanshah, Iran (S Rezaeian PhD); Department of Epidemiology (M B Ahmed MPH), Mycobacteriology Research Center (E Duken MSc), Department of Health Education & Behavioral Sciences (G T Feyissa MPH), Jimma University, Jimma, Ethiopia; University Ferhat Abbas of Setif, Algeria (A Aichour BMedSc, I Aichour BPharm); Higher National School of Veterinary Medicine, Algiers, Algeria (M Aichour MA); The Hospital for Sick Children (N Akseer PhD), Department of Nutritional Sciences (A Badawi PhD), The Centre for Global Child Health, Hospital for Sick Children (Prof Z A Bhutta PhD), University of Toronto, Toronto, ON, Canada; Pediatric Intensive Care Unit (A Al-Eyadhy MD), Department of Pediatrics (B H Sobaih MD, M Temsah MD), King Saud University, Riyadh, Saudi Arabia (K Altirkawi MD); Centre for Clinical Brain Sciences (Prof R Al-Shahi Salman PhD), Usher Institute of Population Health Sciences and Informatics (Prof A Sheikh MD, I N Soyiri PhD), University of Edinburgh, Edinburgh, UK; Evidence-Based Practice Center, Mayo Clinic Foundation for Medical Education and Research, Rochester, MN, USA (F Alahdab MD); Institute of Public Health (K A Alene MPH, B Bekele MPH), Department of Clinical Chemistry (B Biadgo MSc), Department of Medical Microbiology (D Geremew MSc), University of Gondar, Gondar, Ethiopia; Research School of Population Health (K A Alene MPH), National Centre for Epidemiology and Population Health (M Bin Sayeed MSPS, Prof R M Lucas PhD), Australian National University, Canberra, ACT, Australia; Department of Health Policy and Management, Kuwait University, Safat, Kuwait (Prof S M Aljunid PhD); International Centre for Casemix and Clinical Coding, National University of Malaysia, Bandar Tun Razak, Malaysia (Prof S M Aljunid PhD); Research Group on Health Economics, University of Cartagena, Cartagena, Colombia (Prof N Alvis-Guzman PhD); Research Group in Hospital Management and Health Policies, University of the Coast, Barranquilla, Colombia (Prof N Alvis-Guzman PhD); Faculty of Medicine (N H Anber PhD), Mansoura University, Mansoura, Egypt (N H Anber PhD); Department of Health Policy and Administration (C T Antonio MD), Department of Epidemiology and Biostatistics (J F Lopez MD), University of the Philippines Manila, Manila, Philippines; Department of Applied Social Sciences, Hong Kong Polytechnic University, Hong Kong, China (C T Antonio MD); Health Management and Economics Research Center (J Arabloo PhD, M Behzadifar PhD), Preventive Medicine and Public Health Research Center (M Moradi-Lakeh MD, K Vosoughi MD, A Tehrani-Banihashemi PhD), Department of Health Policy (H Shabaninejad PhD), Department of Community Medicine (A Tehrani-Banihashemi PhD), Physiology Research Center (M Yousefifard PhD), Iran University of Medical Sciences, Tehran, Iran (F Farhadi MD); School of Health Sciences, Birmingham City University, Birmingham, UK (O Aremu PhD); Department of Neurobiology (Prof J Ärnlöv PhD), Department of Medical Epidemiology and Biostatistics (J J Carrero PhD, Prof E Weiderpass PhD), Department of Public Health Sciences (Z El-Khatib PhD), Department of Neurobiology, Care Sciences and Society (S Fereshtehnejad PhD), Karolinska Institutet, Stockholm, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden (Prof J Ärnlöv PhD); Qom University of Medical Sciences, Qom, Iran (H Asayesh MSc); South Asian Public Health Forum, Lahore, Pakistan (R J Asghar MPH); Department of Nursing (H T Atalay MSc), Department of Clinical Pharmacy (G T Demoz MSc), Aksum University, Aksum, Ethiopia; Indian Institute of Public Health, Gandhinagar, India (A Awasthi PhD); The Judith Lumley Centre (B Ayala Quintanilla PhD), School of Nursing and Midwifery (Prof D Edvardsson PhD), Austin Clinical School of Nursing (M Rahman PhD), Department of Psychology (Prof T Wijeratne MD), La Trobe University, Melbourne, VIC, Australia; General Office for Research and Technological Transfer, Peruvian National Institute of Health, Lima, Peru (B Ayala Quintanilla PhD); Centre for Food and Nutrition Research, Institute of Medical Research and Medicinal Plant Studies, Yaounde, Cameroon (T B Ayuk PhD); Department of Health Studies, University of South Africa, Pretoria, South Africa (T B Ayuk PhD); Public Health Risk Sciences Division, Public Health Agency of Canada, Toronto, ON, Canada (A Badawi PhD); Department of Hypertension, Medical University of Lodz, Lodz, Poland (Prof M Banach PhD); Polish Mothers’ Memorial Hospital Research Institute, Lodz, Poland (Prof M Banach PhD); Faculty of Medicine, Alexandria University, Alexandria, Egypt (J A M Banoub MD); Department of Transplant Services, University Hospital Foundation Santa Fe de Bogotá, Bogotá, Colombia (J A M Banoub MD); Department of Neurosciences, Costa Rican Department of Social Security, San Jose, Costa Rica (Prof M A Barboza MD); School of Medicine, University of Costa Rica, San Pedro, Costa Rica (Prof M A Barboza MD); School of Psychology (Prof S L Barker-Collo PhD), School of Population Health, Faculty of Medical & Health Science (B J Te Ao PhD), Molecular Medicine and Pathology (K B Tran MD), University of Auckland, Auckland, New Zealand; Institute of Public Health, Heidelberg University Hospital, Heidelberg, Germany (Prof T W Bärnighausen MD); T.H. Chan School of Public Health (Prof T W Bärnighausen MD), Division of General Internal Medicine and Primary Care (Prof A Sheikh MD), Harvard University, Boston, MA, USA; Melbourne Medical School, Melbourne, VIC, Australia (Prof B T Baune PhD); Department of Community Medicine, Gandhi Medical College Bhopal, Bhopal, India (Prof N Bedi MD); Jazan University, Jazan, Saudi Arabia (Prof N Bedi MD); Social Determinants of Health Research Center (M Behzadifar PhD), Lorestan University of Medical Sciences, Khorramabad, Iran (M Behzadifar MSc); Department of Neurology, University Hospital of Dijon, Dijon, France (Prof Y Béjot PhD); Dijon Stroke Registry – UFR Sciences Santé, University of Burgundy, Dijon, France (Prof Y Béjot PhD); Public Health Department (B Bekele MPH, H Y Hassen MPH), Pharmacy Department (A T Kefale MSc), Mizan-Tepi University, Teppi, Ethiopia (A Henok MPH); Nuffield Department of Population Health (D A Bennett PhD, B Lacey DPhil), Department of Psychiatry (Prof C R J Newton MD), University of Oxford, Oxford, UK; Department of Internal Medicine (I M Bensenor PhD, Prof I S Santos PhD), University Hospital, Internal Medicine Department (A C Goulart PhD), Department of Medicine (Prof P A Lotufo DrPH), Department of Psychiatry (G V Polanczyk MD, Y Wang PhD), Department of Pathology and Legal Medicine (M R Tovani-Palone MSc), Center for Clinical and Epidemiological Research (A C Goulart PhD), University of São Paulo, São Paulo, Brazil; School of Public Health (A Berhane PhD, K Deribe PhD, M Y Gidey MSc), Department of Pharmacology and Clinical Pharmacy (O S Muhammed MSc), Public Health (E M Roro MPH), School of Allied Health Sciences (E Yisma MPH), Addis Ababa University, Addis Ababa, Ethiopia (G T Demoz MSc); Emergency Hospital of Bucharest (Prof M Beuran PhD, I Negoi PhD), Anatomy and Embryology Department (R I Negoi PhD), Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Biostatistics and Bioinformatics, National Institute of Biomedical Genomics, Kalyani, India (K Bhattacharyya MSc); Center of Excellence in Women and Child Health (Prof Z A Bhutta PhD), Human Development Programme (B Fatima DrPH), Aga Khan University, Karachi, Pakistan; Social Determinants of Health Research Center (A Bijani PhD), Health Research Institute (M Ghasemi-Kasman PhD), Department of Pharmacology (M Mohammadi-Khanaposhtani PhD), Department of Immunology (M Mohammadnia-Afrouzi PhD), Infectious Diseases and Tropical Medicine Research Center (A Rostami PhD, P Sabbagh PhD), Student Research Committee (M Zamani MD), Babol University of Medical Sciences, Babol, Iran; Woldia University, Woldia, Ethiopia (N Bililign BHlthSci); Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Ramna, Bangladesh (M Bin Sayeed MSPS); Medical School, University of Michigan, Ann Arbor, MI, USA (C K Blazes MD); Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK (Prof C Brayne MD); School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada (Z A Butt PhD, Prof N Sarrafzadegan MD); Al Shifa School of Public Health, Al Shifa Trust Eye Hospital, Rawalpindi, Pakistan (Z A Butt PhD); Center for Evaluation and Surveys Research (V De la Cruz-Góngora PhD), National Institute of Public Health, Cuernavaca, Mexico (I R Campos-Nonato PhD); Department of Neurology, Salvador Zubiran National Institute of Medical Sciences and Nutrition, Mexico City, Mexico (Prof C Cantu-Brito PhD); Ministry of Health, Zagreb, Croatia (M Car PhD); Department of Articles 476 www.thelancet.com/neurology Vol 18 May 2019 Population and Health, Metropolitan Autonomous University, Mexico City, Mexico (Prof R Cárdenas DSc); Institute of Public Health (Prof F Carvalho PhD), UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy (Prof V M Costa PharmD), REQUIMTE/LAQV (Prof E Fernandes PhD, Prof D M Pereira PhD), UCIBIO (J P Silva PhD), Applied Molecular Biosciences Unit (Prof F Carvalho PhD), University of Porto, Porto, Portugal; Colombian National Health Observatory (C A Castañeda-Orjuela MD), National Institute of Health, Bogota, Colombia (C M Rios González MEd); Epidemiology and Public Health Evaluation Group (C A Castañeda-Orjuela MD), Department of Public Health (Prof F P De La Hoz PhD), National University of Colombia, Bogota, Colombia; Department of Research and Health Technology Assessment (F Castro MD), Gorgas Memorial Institute for Health Studies, Panama City, Panama (I Moreno Velásquez PhD); Department of Health Planning and Economics, Institute of Health Carlos III, Madrid, Spain (F Catalá-López PhD); School of Public Health (Prof E Cerin PhD), Centre for Suicide Research and Prevention (Prof P Yip PhD), University of Hong Kong, Hong Kong, China; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia (Y Chaiah, Prof Z A Memish MD, M Temsah MD, O Temsah); College of Medicine, National Taiwan University, Taipei, Taiwan (J Chang PhD); 2nd Department of Ophthalmology, University of Athens, Haidari, Greece (I Chatziralli PhD); Clinical Governance, Gold Coast Health, Gold Coast, QLD, Australia (P P Chiang PhD); Institute of Clinical Medicine and Bispebjerg Hospital (Prof H Christensen DMSci), Department of Neurology (T C Truelsen PhD), University of Copenhagen, Copenhagen, Denmark; Department of Pulmonary Medicine (Prof D J Christopher MD), Department of Neurology (Prof J D Pandian MD), Christian Medical College and Hospital (CMC), Vellore, India; NIHR Oxford Biomedical Research Centre (Prof C Cooper MEd), University of Southampton, Southampton, UK (Prof C Cooper MEd); School of Medicine and Surgery, University of Milan Bicocca, Monza, Italy (P A Cortesi PhD, A Lafranconi MD, Prof L G Mantovani DSc); Department of Family Medicine and Public Health (Prof M H Criqui MD), Department of Psychiatry (M B Stein MD), University of California San Diego, La Jolla, CA, USA; Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique (Prof A A M Damasceno PhD); Toxoplasmosis Research Center (Prof A Daryani PhD, S Sarvi PhD), Department of Neurology (N Karimi MD), Department of Physiology and Pharmacology (M Mohammadi PhD), Health Sciences Research Center (M Moosazadeh PhD), Molecular and Cell Biology Research Center (Prof A Rafiei PhD), Department of Pediatrics (M Rezai MD), Immunogenetics Research Center (N Karimi MD), Department of Immunology (Prof A Rafiei PhD), Mazandaran University of Medical Sciences, Sari, Iran (M Nourollahpour Shiadeh PhD, Z Zare PhD); Australian Institute for Suicide Research and Prevention, Griffith University, Mount Gravatt, QLD, Australia (Prof D De Leo DSc); Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK (K Deribe PhD); Department of Community Medicine, University of Peradeniya, Peradeniya, Sri Lanka (S D Dharmaratne MD); Center of Complexity Sciences, National Autonomous University of Mexico, Mexico City, Mexico (Prof D Diaz PhD); Faculty of Veterinary Medicine and Zootechnics, Autonomous University of Sinaloa, Culiacán, Mexico (Prof D Diaz PhD); Department of Midwifery, Debre Berhan University, Debre Berhan, Ethiopia (M T Dinberu MA); Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran (S Djalalinia PhD); Department of Population and Health, University of Cape Coast, Cape Coast, Ghana (D T Doku PhD); Faculty of Social Sciences, Health Sciences, University of Tampere, Tampere, Finland (D T Doku PhD); United Nations World Food Programme, New Delhi, India (M Dubey PhD); Faculty of Medicine (E Dubljanin PhD), Centre School of Public Health and Health Management (Prof M M Santric Milicevic PhD), Faculty of Medicine Institute of Epidemiology (I S Vujcic PhD), University of Belgrade, Belgrade, Serbia; Department of Health Sciences (E Duken MSc), Department of Public Health (E M Roro MPH), Wollega University, Nekemte, Ethiopia; Department of Nursing, Umeå University, Umea, Sweden (Prof D Edvardsson PhD); Department of Neurology, Charité University Medical Center Berlin, Berlin, Germany (Prof M Endres MD); Public Health Department, Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia (A Y Endries MPH); Department of Psychology, Federal University of Sergipe, Sao Cristovao, Brazil (Prof A Faro PhD); Division of Neurology, University of Ottawa, Ottawa, ON, Canada (S Fereshtehnejad PhD); Psychiatry, Kaiser Permanente, Fontana, CA, USA (I Filip MD); Department of Health Sciences (I Filip MD), A T Still University, Mesa, Arizona, USA (A Radfar MD); Department of Public Health Medicine, Bielefeld University, Bielefeld, Germany (F Fischer PhD); Gene Expression & Regulation Program, Cancer Institute (WIA), Philadelphia, PA, USA (T Fukumoto PhD); Department of Dermatology, Kobe University, Kobe, Japan (T Fukumoto PhD); Faculty of Medicine and Pharmacy of Fez, University Sidi Mohammed Ben Abdellah, Fez, Morocco (F G Gankpe MD); Non Communicable Disease Department, Laboratory of Studies and Research-Action in Health, Porto Novo, Benin (F G Gankpe MD); Faculty of Business and Management (M A Garcia-Gordillo PhD), Institute of Physical Activity and Health (Prof P R Olivares PhD), Autonomous University of Chile, Talca, Chile; School of Pharmacy, Ambo University, Ambo, Ethiopia (B K Gelaw MSc); Division of Human Nutrition and Health, Wageningen University& Research, Wageningen, Netherlands (Prof J M Geleijnse PhD); Research, Performance Monitoring and Accountability 2020-Ethiopia, Addis Ababa, Ethiopia (M Y Gidey MSc); Unit of Academic Primary Care (Prof P S Gill DM), Division of Health Sciences (O A Uthman PhD), University of Warwick, Coventry, UK; Adelaide Medical School (T K Gill PhD), University of Adelaide, Adelaide, SA, Australia (A T Olagunju MD); Research Center of Neurology, Moscow, Russia (E V Gnedovskaya PhD, Prof M A Piradov DSc); School of Medicine, Boston University, Boston, MA, USA (A Grada MD); Registro Tumori Integrato, Vittorio Emanuele University Hospital Polyclinic, Catania, Italy (G Grosso PhD); Commissioner of Public Health, West Virginia Bureau for Public Health, Charleston, WV, USA (Prof R Gupta MD); Department of Health Policy, Management & Leadership, West Virginia University School of Public Health, Morgantown, WV, USA (Prof R Gupta MD); Academics and Research, Rajasthan University of Health Sciences, Jaipur, India (Prof R Gupta MD); Department of Preventive Cardiology, Eternal Heart Care Centre & Research Institute, Jaipur, India (Prof R Gupta MD); Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands (J A Haagsma PhD, S Polinder MA); Research Institute for Endocrine Sciences (Arv Haj-Mirzaian MD, S N Irvani MD), Ophthalmic Epidemiology Research Center (S Safi PhD), Ophthalmic Research Center (M Yaseri PhD, S Safi PhD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Radiology (Ary Haj-Mirzaian MD), Department of Gastroenterology and Hepatology (K Vosoughi MD), Johns Hopkins University, Baltimore, MD, USA; Department of Family and Community Medicine, Arabian Gulf University, Manama, Bahrain (Prof R R Hamadeh DPhil); School of Health and Environmental Studies, Hamdan Bin Mohammed Smart University, Dubai, United Arab Emirates (Prof S Hamidi DrPH); School of Medicine (Prof G J Hankey MD), Lions Eye Institute (Prof R M Lucas PhD), University of Western Australia, Perth, WA, Australia; Neurology Department, Sir Charles Gairdner Hospital, Perth, WA, Australia (Prof G J Hankey MD); Sun Yat-sen Global Health Institute (Prof Y Hao PhD), Department of Medical Statistics and Epidemiology (Y Liao PhD, Prof Y Hao PhD), Sun Yat-sen University, Guangzhou, China; Research and Development Unit, San Juan de Dios Sanitary Park, Sant Boi De Llobregat, Spain (Prof J M Haro MD, A Koyanagi MD); Department of Medicine, University of Barcelona, Barcelona, Spain (Prof J M Haro MD); Tabriz University of Medical Sciences, Tabriz, Iran (H Hassankhani PhD); Independent Consultant, Tabriz, Iran (H Hassankhani PhD); Unit of Epidemiology and Social Medicine, University Hospital Antwerp, Wilrijk, Belgium (H Y Hassen MPH); Clinical Sciences, Karolinska University Hospital, Stockholm, Sweden (R Havmoeller PhD); Endocrinology and Metabolism Research Center, Teikyo University School of Medicine, Tehran, Iran (B Heidari MD); Center of Excellence in Behavioral Medicine (C L Hoang BMedSc, G T Vu BA), Center for Excellence in Behavioral Health (L H Nguyen PhD), Nguyen Tat Thanh University, Ho Chi Minh, Vietnam; University of Texas Austin, Austin, TX, USA (M K Hole MD); School of Health (E Homaie Rad PhD), Guilan Road Trauma Research Center (E Homaie Rad PhD), Guilan University of Medical Sciences, Rasht, Iran; Department of Epidemiology and Health Statistics, Central South University, Changsha, China (Prof G Hu PhD); School of Public Health, University of the Western Cape, Bellville, Cape Town, South Africa Articles www.thelancet.com/neurology Vol 18 May 2019 477 (Prof E U Igumbor PhD); Department of Public Health, Walter Sisulu University, Mthatha, South Africa (Prof E U Igumbor PhD); Department of Public Health and Community Medicine, University of Liberia, Monrovia, Liberia (O S Ilesanmi PhD); Institute for Physical Activity and Nutrition (S Islam PhD), National Centre for Farmer Health (M Rahman PhD), Department of Psychology (M A Stokes PhD), Deakin University, Burwood, VIC, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia (S Islam PhD); Medical Sciences Department, University of Kragujevac, Kragujevac, Serbia (Prof M Jakovljevic PhD); Newcastle University, Tyne, UK (M Javanbakht PhD); Department of Community Medicine, Banaras Hindu University, Varanasi, India (R P Jha MSc); Department of Medicine (Y B Jobanputra MD), Department of Neurology (Prof R L Sacco MD), University of Miami, Atlantis, FL, USA; Department of Ophthalmology (Prof J B Jonas MD), Medical Clinic V (Prof W März MD), Institute of Public Health (B Moazen MSc, S Mohammed PhD), Augenpraxis Jonas (S Panda-Jonas MD), Heidelberg University, Mannheim, Germany; Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, China (Prof J B Jonas MD); Faculty of Medicine and Health Sciences (J J Jozwiak PhD), Department of Family Medicine and Public Health (J J Jozwiak PhD), University of Opole, Opole, Poland; Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia (M Jürisson PhD); Public Health, Society for Education, Action and Research in Community Health, India (Y Kalkonde MD); School of Public Health, Department of Health Informatics and Health Innovation (T Kamil MSc), ACS Medical College and Hospital, Mekelle, Ethiopia (Prof Z Zaidi DrPH); Department of Forensic Medicine and Toxicology (T Kanchan MD), Department of Psychiatry (Prof R Sagar MD), All India Institute of Medical Sciences, Jodhpur, India; Department of Epidemiology (M Karami PhD), Biostatistics (N Mohammad Gholi Mezerji MSc), Health (Prof R Mohammadibakhsh PhD), Chronic Diseases (Home Care) Research Center (M Shamsizadeh MSc), Hamadan University of Medical Sciences, Hamadan, Iran; Department for Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany (A Karch MD); School of Nursing and Midwifery, Hawassa University, Hawassa, Ethiopia (Z Y Kassa MSc); School of Health Care Administration, Oklahoma State University, Tulsa, OK, USA (Prof A Kaul MD); Health Care Delivery Sciences, University of Tulsa, Tulsa, OK, USA (Prof A Kaul MD); ODeL Campus (Prof P N Keiyoro PhD), Department of Psychiatry (M Kumar PhD), University of Nairobi, Nairobi, Kenya; Department of Public Health and Community Medicine, Jordan University of Science and Technology, Ramtha, Jordan (Prof Y S Khader PhD); Department of Public Health (M A Khafaie PhD), Thalassemia and Hemoglobinopathy Research Center (F Rahim PhD), Department of Neurosurgery (H Safari MD), Medical Physics Department (A Yadollahpour PhD), Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Epidemiology and Biostatistics Department, Health Services Academy, Islamabad, Pakistan (E A Khan MPH); Institute of Health Policy and Management (Prof Y Khang MD), Department of Health Policy and Management (Prof Y Khang MD), Seoul National University, Seoul, South Korea; Clinical Epidemiology Unit (A A Kiadaliri PhD), Department of Clinical Sciences (Prof B Norrving PhD), Lund University, Lund, Sweden; Research Department, Kenya Revenue Authority, Nairobi, Kenya (D N Kiirithio MSc); Research and Data Solutions, Synotech Consultant, Nairobi, Kenya (D N Kiirithio MSc); Department of Neurology, University of California San Francisco, San Francisco, CA, USA (A S Kim MD); Department of Health Sciences, Northeastern University, Boston, MA, USA (Prof D Kim DrPH); Department of Preventive Medicine, Korea University, Seoul, South Korea (Y Kim PhD); School of Medicine, Xiamen University Malaysia, Sepang, Malaysia (Y Kim PhD); Department of Health Management and Health Economics (Prof A Kisa PhD), Institute of Health and Society (A S Winkler PhD), University of Oslo, Oslo, Norway; Department of Global Community Health and Behavioral Sciences, Tulane University, New Orleans, LA, USA (Prof A Kisa PhD); Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan (Prof Y Kokubo PhD); Department of Social and Preventive Medicine (Prof B Kuate Defo PhD), Department of Demography (Prof B Kuate Defo PhD), University of Montreal, Montreal, QC, Canada; Department of Public Health, Yuksek Ihtisas University, Ankara, Turkey (B Kucuk Bicer BEP); Department of Public Health, Hacettepe University, Ankara, Turkey (B Kucuk Bicer BEP); Department of Psychology, University College London, London, UK (M Kumar PhD); NIHR Oxford Biomedical Research Centre, Oxford, UK (B Lacey DPhil); Helpmesee, New York, NY, USA (Prof V C Lansingh PhD); International Relations, Mexican Institute of Ophthalmology, Queretaro, Mexico (Prof V C Lansingh PhD); Department of Public Health (A Latifi PhD), Managerial Epidemiology Research Center (S Safiri PhD), Maragheh University of Medical Sciences, Maragheh, Iran; Department of Public Health (C T Leshargie MPH), Department of Nursing (F S Wagnew MSc), Debre Markos University, Debre Markos, Ethiopia; Alliance for Improving Health Outcomes, Inc., Quezon City, Philippines (Y Liao PhD); School of Public Health, University of Haifa, Haifa, Israel (Prof S Linn DrPH); Department of Pediatric Neurology, Nationwide Children’s Hospital, Columbus, Ohio, USA (W D Lo MD); Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany (Prof S Lorkowski PhD); Innovation Office (T Meier PhD), Competence Cluster for Nutrition and Cardiovascular Health (NUTRICARD), Jena, Germany (Prof S Lorkowski PhD); General Surgery Department, Aintree University Hospital National Health Service Foundation Trust (NHS), Liverpool, UK (R Lunevicius PhD); Surgery Department, University of Liverpool, Liverpool, UK (R Lunevicius PhD); Neurology Department, Royal Children’s Hospital, Melbourne, VIC, Australia (M T Mackay PhD); Institute of Medicine, Tribhuvan University, Kathmandu, Nepal (N B Mahotra MD); Department of Public Health, Trnava University, Trnava, Slovakia (M Majdan PhD); Non-communicable Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran (Prof R Malekzadeh MD, S G Sepanlou MD); Department of Maternal and Child Nursing and Public Health, Federal University of Minas Gerais, Belo Horizonte, Brazil (Prof D C Malta PhD); Ophthalmology, IUMS, Tehran, Iran (N Manafi MD); Ophthalmology, University of Manitoba, Winnipeg, MB, Canada (N Manafi MD); Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria (Prof W März MD); Department of Public Health Medicine, University of Kwazulu-Natal, South Africa (T P Mashamba-Thompson PhD, Y Moodley PhD, Prof B Sartorius PhD); Department of Ophthalmology, Hywel Dda University Health Board, Carmarthen, UK (C McAlinden PhD, E Skiadaresi MD); Queensland Brain Institute (Prof J J McGrath MD), The University of Queensland, Brisbane, QLD, Australia (Prof H A Whiteford PhD); National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark (Prof J J McGrath MD); Department of Internal Medicine, Sevenhills Hospital, Mumbai, India (V Mehta MD); Institute for Agricultural and Nutritional Sciences (T Meier PhD), Institute of Medical Epidemiology (I Shiue PhD), Martin Luther University Halle-Wittenberg, Halle, Germany; College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia (A Melese MSc); Department of Public Health, University of West Florida, Pensacola, FL, USA (P T N Memiah DrPH); Research Department Prince Mohammed Bin Abdulaziz Hospital, Ministry of Health, Riyadh, Saudi Arabia (Prof Z A Memish MD); Peru Country Office, United Nations Population Fund (UNFPA), Lima, Peru (W Mendoza MD); School of Pharmacy, Haramaya University, Harar, Ethiopia (G Mengistu MSc); Department of Pharmacy, Wollo University, Dessie, Ethiopia (G Mengistu MSc); Neurocenter (A Meretoja MD), Breast Surgery Unit (T J Meretoja MD), Helsinki University Hospital, Helsinki, Finland; University of Helsinki, Helsinki, Finland (T J Meretoja MD); Clinical Microbiology and Parasitology Unit, Dr. Zora Profozic Polyclinic, Zagreb, Croatia (T Mestrovic PhD); University Centre Varazdin, University North, Varazdin, Croatia (T Mestrovic PhD); Department of Hypertension (Prof T Miazgowski MD), Emergency Department (B Miazgowski MD), Pomeranian Medical University, Szczecin, Poland (B Miazgowski MD); Pacific Institute for Research & Evaluation, Calverton, MD, USA (T R Miller PhD); School of Public Health, Curtin University, Perth, WA, Australia (T R Miller PhD); Achutha Menon Centre for Health Science Studies (GK Mini PhD), Neurology Department (Prof P Sylaja MD), Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India (Prof P Sylaja MD); Department of Public Health, Amrita Institute of Medical Sciences, Kochi, India (GK Mini PhD); Faculty of General Medicine, Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan (Prof E M Mirrakhimov MD); Department of Atherosclerosis and Coronary Heart Disease, National Center of Cardiology and Internal Disease, Bishkek, Kyrgyzstan (Prof E M Mirrakhimov MD); Institute of Addiction Research (ISFF), Frankfurt University of Applied Sciences, Frankfurt, Articles 478 www.thelancet.com/neurology Vol 18 May 2019 Germany (B Moazen MSc); Hamedan University of Medical Sciences, Hamedan, Iran (Prof R Mohammadibakhsh PhD); Health Systems and Policy Research Unit (S Mohammed PhD), Department of Community Medicine (M B Sufiyan MD), Ahmadu Bello University, Zaria, Nigeria; Clinical Epidemiology and Public Health Research Unit, Burlo Garofolo Institute for Maternal and Child Health, Trieste, Italy (L Monasta DSc, L Ronfani PhD); Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy (S Mondello MD); Department of Neurology, Oasi Research Institute, Troina, Italy (S Mondello MD); Department of Epidemiology and Biostatistics (G Moradi PhD), Social Determinants of Health Research Center (G Moradi PhD), Kurdistan University of Medical Sciences, Sanandaj, Iran; Lancaster University, Lancaster, UK (P Moraga PhD); School of Population Health and Environmental Sciences (W Muruet MSc), School of Population Health & Environmental Sciences (Prof C D A Wolfe MD), King’s College London, London, UK; School of Medical Sciences, Science University of Malaysia, Kubang Kerian, Malaysia (K Musa PhD); Pediatrics Department, Nishtar Medical University, Multan, Pakistan (Prof G Mustafa MD); Pediatrics & Pediatric Pulmonology, Institute of Mother & Child Care, Multan, Pakistan (Prof G Mustafa MD); Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany (Prof G Nagel PhD); Initiative for Non Communicable Diseases (A Naheed PhD), Maternal and Child Health Division (S Zaman MPH), International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh; Department of Epidemiology (G Naik MPH, J A Singh MD), Department of Psychology (D C Schwebel PhD), Department of Medicine (J A Singh MD), University of Alabama at Birmingham, Birmingham, AL, USA (A R Sawant MD); Suraj Eye Institute, Nagpur, India (V Nangia MD); Department of Cardiology, Cardio-Aid, Bucharest, Romania (R I Negoi PhD); Neurosciences, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya (Prof C R J Newton MD); Department of Biological Sciences, University of Embu, Embu, Kenya (J W Ngunjiri DrPH); Institute for Global Health Innovations, Duy Tan University, Hanoi, Vietnam (C T Nguyen MPH); Public Health Science Department, State University of Semarang, Kota Semarang, Indonesia (D N A Ningrum MPH); Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei City, Taiwan (D N A Ningrum MPH); Department of Medicine (J Noubiap MD), Department of Psychiatry and Mental Health (Prof D J Stein MD), University of Cape Town, Cape Town, South Africa; Western Sydney University, Penrith, NSW, Australia (F A Ogbo PhD); Department of Preventive Medicine, Kyung Hee University, Dongdaemun-gu, South Korea (I Oh PhD); Department of Psychiatry, University of Lagos, Lagos, Nigeria (A T Olagunju MD); Department of Pathology and Molecular Medicine, Mcmaster University, Hamilton, ON, Canada (T O Olagunju MD); Department of Pharmacology and Therapeutics, University of Nigeria Nsukka, Enugu, Nigeria (Prof O E Onwujekwe PhD); Graduate School of Public Health, San Diego State University, San Diego, CA, USA (Prof E Oren PhD); Department of TB & Respiratory Medicine, Jagadguru Sri Shivarathreeswara University, Mysore, India (Prof M P A DNB); Department of Public Health, Qazvin University of Medical Sciences, Qazvin, Iran (Prof A H Pakpour PhD); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (Prof W Pan PhD); Research and Evaluation, Population Council, New Delhi, India (S K Patel PhD); Indian Institute of Health Management Research University, Jaipur, India (S K Patel PhD); Cartagena University, Cartagena, Colombia (Prof D M Pereira PhD); Institute of Medicine, University of Gothenburg, Gothenburg, Sweden (Prof M Petzold PhD); School of Public Health, University of Witwatersrand, Johannesburg, South Africa (Prof M Petzold PhD); Basic Medical Sciences Department, Durban University of Technology, Durban, South Africa (J D Pillay PhD); Department of Economics and Business (Prof M J Postma PhD), University Medical Center Groningen (Prof M J Postma PhD), University of Groningen, Groningen, Netherlands; Department of Psychology (Prof R Poulton PhD), Department of Medicine (A Ranta PhD), University of Otago, Dunedin, New Zealand; Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (S Prakash PhD); Askok & Rita Patel Institute of Physiotherapy, Charotar University of Science and Technology, Anand, India (V Prakash PhD); Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran (M Qorbani PhD); Medichem, Barcelona, Spain (A Radfar MD); Department of Epidemiology & Biostatistics, Contech School of Public Health, Lahore, Pakistan (A Rafay MS); Research and Evaluation Division, Brac University, Dhaka, Bangladesh (M Rahman PhD); Department of Public Health and Mortality Studies (M Rahman PhD), Department of Public Health & Mortality Studies (Prof U Ram PhD), International Institute for Population Sciences, Mumbai, India; Department of Neurology, Capital & Coast District Health Board, Wellington, New Zealand (A Ranta PhD); University College London Hospitals, London, UK (D L Rawaf MD); Public Health England, London, UK (Prof S Rawaf PhD); Department of Preventive Medicine and Occupational Medicine, Loma Linda University Medical Center, Loma Linda, CA, USA (C Reis MD); School of Social Sciences and Psychology, Western Sydney University, Penrith, NSW, Australia (Prof A M N Renzaho PhD); Brien Holden Vision Institute, Sydney, NSW, Australia (Prof S Resnikoff MD); Organization for the Prevention of Blindness, Paris, France (Prof S Resnikoff MD); Research Directorate, Nihon Gakko University, Fernando De La Mora, Paraguay (C M Rios González M Ed); Department of Clinical Research, Federal University of Uberlândia, Uberlândia, Brazil (L Roever PhD); Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran (G Roshandel PhD); School of Psychiatry, University of New South Wales, Kensington, NSW, Australia (Prof P S Sachdev MD); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia (Prof P S Sachdev MD); Medical Department, University of Sharjah, Sharjah, United Arab Emirates (B Saddik PhD); Internal Medicine Servcies, Ballarat Health Service, Ballarat, VIC, Australia (R Sahathevan PhD); Neurogenic Inflammation Research Center (A Sahebkar PhD), Biotechnology Research Center (A Sahebkar PhD), Mashhad University of Medical Sciences, Mashhad, Iran; School of Health and Policy Management, Faculty of Health, York University, Toronto, ON, Canada (Prof P Salamati MD); Research Deputy, Taleghani Hospital, Kermanshah, Iran (S Salehi Zahabi PhD); Department of Entomology, Ain Shams University, Cairo, Egypt (A M Samy PhD); Department of Surgery, Marshall University, Huntington, WV, USA (Prof J Sanabria MD); Department of Nutrition and Preventive Medicine, Case Western Reserve University, Cleveland, OH, USA (Prof J Sanabria MD); Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran (Prof N Sarrafzadegan MD); Surgery Department, Hamad Medical Corporation, Doha, Qatar (B Sathian PhD); Faculty of Health & Social Sciences, Bournemouth University, Bournemouth, UK (B Sathian PhD); UGC Centre of Advanced Study in Psychology, Utkal University, Bhubaneswar, India (M Satpathy PhD); Udyam-Global Association for Sustainable Development, Bhubaneswar, India (M Satpathy PhD); Dr. D.Y. Patil Vidyapeeth, Pune, India (A R Sawant MD); Department of Public Health Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA (M Sawhney PhD); School of Health Sciences, Federal University of Santa Catarina, Ararangua, Brazil (Prof I J C Schneider PhD); Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany (B Schöttker PhD); Langone Medical Center, New York University, New York, NY, USA (A Shafieesabet MD); Independent Consultant, Karachi, Pakistan (M A Shaikh MD); School of Medicine, Dezful University of Medical Sciences, Dezful, Iran (M Shams-Beyranvand MSc); Department of Laboratory Sciences (Prof M Sharif PhD), Department of Basic Sciences (Prof M Sharif PhD), Islamic Azad University, Sari, Iran; Department of Pulmonary Medicine, Fudan University, Shanghai, China (J She MD); Department of Neurology, Yale University, New Haven, CT, USA (K N Sheth MD); National Institute of Infectious Diseases, Tokyo, Japan (M Shigematsu PhD); Finnish Institute of Occupational Health, Helsinki, Finland (R Shiri PhD); School of Health, University of Technology Sydney, Sydney, NSW, Australia (S Siabani PhD); Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan (T J Siddiqi MB, M S Usman MB); Department of Psychology, Reykjavik University, Reykjavik, Iceland (Prof I D Sigfusdottir PhD, R Sigurvinsdottir PhD); Department of Health and Behavior Studies, Columbia University, New York, NY, USA (Prof I D Sigfusdottir PhD); Department of Neurology (D H Silberberg MD), Population Studies Center (J Weiss MA), University of Pennsylvania, Philadelphia, PA, USA; Brasília University, Brasília, Brazil (Prof D A Silveira MD); Department of the Health Industrial Complex and Innovation in Health, Federal Ministry of Health, Brasília, Articles www.thelancet.com/neurology Vol 18 May 2019 479 Brazil (Prof D A Silveira MD); Department of Epidemiology, School of Preventive Oncology, Patna, India (D N Sinha PhD); Department of Epidemiology, Healis Sekhsaria Institute for Public Health, Mumbai, India (D N Sinha PhD); Pediatric Department, King Khalid University Hospital, Riyadh, Saudi Arabia (S Sobhani MD); Hull York Medical School, University of Hull, Hull City, UK (I N Soyiri PhD); Clinical Neurological Sciences, The University of Western Ontario, London, ON, Canada (L A Sposato MD); Department of Criminology, Law and Society, University of California Irvine, Irvine, CA, USA (Prof B L Sykes PhD); Department of Medicine (Prof R Tabarés-Seisdedos PhD), Department of Pediatrics, Obstetrics and Gynecology (Prof M Tortajada-Girbés PhD), University of Valencia, Valencia, Spain; Carlos III Health Institute, Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Madrid, Spain (Prof R Tabarés-Seisdedos PhD); School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, India (Prof J S Thakur MD); Institute of Public Health, Jagiellonian University Medical College, Krakow, Poland (R Topor-Madry PhD); Agency for Health Technology Assessment and Tariff System, Warszawa, Poland (R Topor-Madry PhD); Pediatric Department, University Hospital Doctor Peset, Valencia, Spain (Prof M Tortajada-Girbés PhD); Department of Health Economics, Hanoi Medical University, Hanoi, Vietnam (B X Tran PhD); Clinical Hematology and Toxicology, Military Medical University, Hanoi, Vietnam (K B Tran MD); Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore (L Tudor Car PhD); Department of Internal Medicine, Federal Teaching Hospital, Abakaliki, Nigeria (K N Ukwaja MD); Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, Pakistan (I Ullah PhD); TB Culture Laboratory, Mufti Mehmood Memorial Teaching Hospital, Dera Ismail Khan, Pakistan (I Ullah PhD); Argentine Society of Medicine, Ciudad De Buenos Aires, Argentina (Prof P R Valdez M Ed); Velez Sarsfield Hospital, Buenos Aires, Argentina (Prof P R Valdez M Ed); UKK Institute, Tampere, Finland (Prof T J Vasankari MD); Department of Neurophysiotherapy, The Oxford College of Physiotherapy, Bangalore, India (R Vasanthan); Psychosocial Injuries Research Center, Ilam University of Medical Sciences, Ilam, Iran (Y Veisani PhD); Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore (Prof N Venketasubramanian PhD); Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore (Prof N Venketasubramanian PhD); Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (Prof F S Violante MPH); Occupational Health Unit, Sant’orsola Malpighi Hospital, Bologna, Italy (Prof F S Violante MPH); Department of Health Care Administration and Economy, National Research University Higher School of Economics, Moscow, Russia (Prof V Vlassov MD); Foundation University Medical College, Foundation University, Rawalpindi, Pakistan (Y Waheed PhD); Department of Research, Cancer Registry of Norway, Oslo, Norway (Prof E Weiderpass PhD); Department of Neurology, Technical University of Munich, Munich, Germany (A S Winkler PhD); Cochrane South Africa, Medical Research Council South Africa, Cape Town, South Africa (Prof C S Wiysonge MD); Biomedical Research Council, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK (Prof C D A Wolfe MD); School of Medicine, Nanjing University, Nanjing, China (Prof G Xu MD); Department of Diabetes and Metabolic Diseases, University of Tokyo, Tokyo, Japan (T Yamada MD); Department of Preventive Medicine, Northwestern University, Chicago, IL, USA (Y Yano MD); Department of Public Health, Fujita Health University, Toyoake, Japan (Prof H Yatsuya PhD); Department of Public Health and Health Systems, Nagoya University, Nagoya, Japan (Prof H Yatsuya PhD); Department of Psychopharmacology, National Center of Neurology and Psychiatry, Tokyo, Japan (N Yonemoto MPH); Global Health Institute (Prof C Yu PhD), Department of Preventive Medicine (Y Zhang MPH), Department of Epidemiology and Biostatistics (Prof C Yu PhD), Wuhan University, Wuhan, China; Department of Epidemiology, University Hospital of Setif, Setif, Algeria (Prof Z Zaidi DrPH); and Social Determinants of Health Research Center, Ardebil University of Medical Science, Ardabil, Iran (H Zandian PhD). Contributors VLF and TL prepared the first draft. EN, VLF, and TV analysed the data and edited the first draft and final versions of the manuscript. VLF and TL finalised all drafts and approved the final version of the manuscript. All other authors provided data, developed models, reviewed results, provided guidance on methodology, or reviewed the manuscript, and approved the final version of the manuscript. Declaration of interests CATA reports personal fees from Johnson & Johnson (Philippines), outside the submitted work. JÄ reports lecturing fees from AstraZeneca, outside the submitted work. YB reports personal fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Bristol-Myers Squibb (BMS), Pfizer, Medtronic, Bayer, Novex Pharma, Merck Sharp & Dohme (MSD), and grants from AstraZeneca and Boehringer Ingelheim, outside the submitted work. CC reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GlaxoSmithKline (GSK), Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB, outside the submitted work. JJJ reports grants and personal fees from Valeant, personal fees from ALAB Laboratoria and Amgen, and non-financial support from Microlife and Servier, outside the submitted work. ASK reports grants from SanBio and Biogen, personal fees from Neuravi, and other financial support from Sanofi, outside the submitted work. SLo reports personal fees from Amgen, Berlin-Chemie, MSD, Novo Nordisk, Sanofi-Aventis, Synlab, Unilever, and non-financial support from Preventicus, outside the submitted work; SLo is a member of the Scientific Board of the German Nutrition Society and a co-author of the evidence-based guideline Fat Intake and Prevention of Nutrition-Related Diseases published by the German Nutrition Society. WMä reports grants and personal fees from Siemens Diagnostics, Aegerion Pharmaceuticals, Amgen, AstraZeneca, Danone Research, Pfizer, BASF, Numares AG, and Berlin-Chemie, personal fees from Hoffmann LaRoche, MSD, Sanofi, and Synageva, grants from Abbott Diagnostics, and other financial support from Synlab Holding Deutschland GmbH, outside the submitted work. GVP reports personal fees from Shire, Teva, Medice, and Editora Manole, outside the submitted work. MJP reports grants and personal fees from Sigma Tau, MSD, GSK, Pfizer, Boehringer Ingelheim, Novavax, Ingress Health, AbbVie, and Sanofi, grants from AstraZeneca, ARTEG, Mundipharma, Bayer, and BMS; personal fees from Quintiles, Astellas, Mapi, OptumInsight, Novartis, Swedish Orphan, Innoval, Janssen, Intercept, and Pharmerit, other financial relationships with Ingress Health and PAG Ltd, and grants, personal fees, non-financial support, and other relationships with Asc Academics, outside the submitted work. RAS is the Chair of the ICD11 Neuroscience Topic Advisory Group and the past president of the World Federation of Neurology. JAS reports consulting activities with Horizon, Fidia, UBM LLC, Medscape, WebMD, the National Institutes of Health and the American College of Rheumatology, serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA Inc, a 501c3 entity, and is on the steering committee of OMERACT, an international organisation that develops measures for clinical trials and receives funding from 12 pharmaceutical companies (Amgen, Janssen, Novartis, Roche, UCB Group, Ardea/AstraZeneca, BMS, Celgene, Eli Lilly, Horizon Pharma, Pfizer, and Centrexion). AGT reports grants from National Health and Medical Research Council (NHMRC), Australia, during the conduct of the study, and grants from NHMRC, outside the submitted work. All other authors declare no competing interests. Acknowledgments ROA is funded by the National Institutes of Health (U01HG010273). SMA acknowledges the International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia and Department of Health Policy and Management, Faculty of Public Health, Kuwait University for the approval and support to participate in this research project. AAw acknowledges funding support from Department of Science and Technology, Government of India, New Delhi, through INSPIRE Faculty scheme. TBA acknowledges partial funding from the Institute of Medical Research and Medicinal Plant Studies. ABa is supported by the Public Health Agency of Canada. TWB was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor Award, funded by the Federal Ministry of Education and Research. MSBS acknowledges support from the Australian Government Research and Training Program scholarship for a PhD degree at the Australian National University, Australia. JJC is supported by the Swedish Heart and Lung Foundation. FCar is supported by the European Union (FEDER funds POCI/01/0145/FEDER/007728 and POCI/01/0145/ Articles 480 www.thelancet.com/neurology Vol 18 May 2019 FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreements PT2020 UID/MULTI/04378/2013 and PT2020UID/QUI/50006/2013. EC is supported by an Australian Research Council Future Fellowship (FT3 140100085). KD is supported by a Wellcome Trust [Grant Number 201900] as part of his International Intermediate Fellowship. EF is supported by the European Union (FEDER funds POCI/01/0145/FEDER/007728 and POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreements PT2020 UID/MULTI/04378/2013 and PT2020UID/QUI/50006/2013. SMSI is funded by the Institute for Physical Activity and Nutrition (IPAN), Deakin University and received funding from High Blood Pressure Research Council of Australia. YKa is a DBT/Wellcome Trust India Alliance Fellow in Public Health. YJK is supported by the Office of Research and Innovation at Xiamen University Malaysia. BL acknowledges funding from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. WDL is supported in part by U10NS086484 NINDS. SLo is funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1411A). RML is supported by a National Health and Medical Research Council (NHMRC) of Australia Senior Research Fellowship. AMa and the Imperial College London are grateful for support from the NW London NIHR Collaboration for Leadership in Applied Health Research and Care. JJM is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the John Cade Fellowship (APP1056929) from NHMRC. TMei acknowledges additional institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Jena-Halle-Leipzig. IMV is supported by the Sistema Nacional de Investigación (Panama). MOO is supported by SIREN U54 U54HG007479 and SIBS Genomics R01NS107900 grants. AMS was supported by a fellowship from the Egyptian Fulbright Mission Program. MMSM acknowledges the support from the Ministry of Education, Science and Technological Development, Republic of Serbia (contract no 175087). AShe is supported by Health Data Research UK. MBS’ work on traumatic brain injury is supported by grants NIH U01 NS086090 (PI G Manley) from the National Institutes of Health (NIH) and DoD W81XWH-14–2-0176 (PI G Manley) from the United States Department of Defense. RTS is supported in part by grant number PROMETEOII/2015/021 from Generalitat Valenciana and the national grant PI17/00719 from ISCIIIFEDER. AGT was supported by a Fellowship from the NHMRC (Australia; 1042600. KBT acknowledges funding supports from the Maurice Wilkins Centre for Biodiscovery, Cancer Society of New Zealand, Health Research Council, Gut Cancer Foundation, and the University of Auckland. CY acknowledges support from the National Natural Science Foundation of China (grant number 81773552) and the Chinese NSFC International Cooperation and Exchange Program (grant number 71661167007). References 1 United Nations General Assembly. Progress on the prevention and control of non-communicable diseases. Report of the SecretaryGeneral. 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