Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.

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

Summary Background Neurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses. Methods Through a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn and Yahr scale and assigned disability weights to each level. We jointly modelled prevalence and excess mortality risk in a natural history model to derive estimates of deaths due to Parkinson's disease. Death counts were multiplied by values from the Global Burden of Disease study's standard life expectancy to compute years of life lost. Disability-adjusted life-years (DALYs) were computed as the sum of years lived with disability and years of life lost. We also analysed results based on the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, 6·1 million (95% uncertainty interval [UI] 5·0–7·3) individuals had Parkinson's disease globally, compared with 2·5 million (2·0–3·0) in 1990. This increase was not solely due to increasing numbers of older people, because age-standardised prevalence rates increased by 21·7% (95% UI 18·1–25·3) over the same period (compared with an increase of 74·3%, 95% UI 69·2–79·6, for crude prevalence rates). Parkinson's disease caused 3·2 million (95% UI 2·6–4·0) DALYs and 211 296 deaths (95% UI 167 771–265 160) in 2016. The male-to-female ratios of age-standardised prevalence rates were similar in 2016 (1·40, 95% UI 1·36–1·43) and 1990 (1·37, 1·34–1·40). From 1990 to 2016, age-standardised prevalence, DALY rates, and death rates increased for all global burden of disease regions except for southern Latin America, eastern Europe, and Oceania. In addition, age-standardised DALY rates generally increased across the Socio-demographic Index. Interpretation Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors. Demographic and potentially other factors are poised to increase the future burden of Parkinson's disease substantially. Funding Bill & Melinda Gates Foundation.

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Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Global, regional, and national burden of neurological disorders during 1990-2015

The neuroscience of exercise is a growing research area that is dedicated to furthering our understanding of the effects that exercise has on mental health and athletic performance. The present study examined three specific topics: (1) the relationship between exercise and mental disorders (e.g. major depressive disorder, dementia and Parkinson's disease), (2) the effects of exercise on the mood and mental health of athletes, and (3) the possible neurobiological mechanisms that mediate the effects of exercise. Positive responses to regular physical exercise, such as enhanced functional capacity, increased autonomy and improved self-esteem, are frequently described in the recent literature, and these responses are all good reasons for recommending regular exercise. In addition, physical exercise may improve both mood and adherence to an exercise program in healthy individuals and might modulate both the performance and mental health of athletes. Exercise is associated with the increased synthesis and release of both neurotransmitters and neurotrophic factors, and these increases may be associated with neurogenesis, angiogenesis and neuroplasticity. This review is a call-to-action that urges researchers to consider the importance of understanding the neuroscience of physical exercise and its contributions to sports science.

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Neuroscience of Exercise: From Neurobiology Mechanisms to Mental Health

Parkinson’s disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics.

Parkinson's Disease: From Pathogenesis to Pharmacogenomics

https://www.jstage.jst.go.jp/article/jea/19/6/19_JE20081034/_pdf

Systematic Review of the Prevalence and Incidence of Parkinson's Disease in Asia

Background : A number of epidemiologic studies of Parkinson’s disease (PD) have been conducted worldwide over the years. Although every study reported the rise in prevalence and incidence rate of PD with the increasing age, the overall estimates were different across countries. The variation in reported data may partly be contributed by case ascertainment, case finding method, data collection, and most importantly different population structures. Objective : Systematically review prevalence and incidence of PD and find the causes of variation in the results. Material and Method : A literature search was conducted on Medline and EMBASE for studies worldwide investigating the prevalence and incidence of PD and included all adults, English and publication between 1965 and January 2010.The primary search of both databases yielded 5,330 results. After screening topics and abstracts, 168 relevant abstracts were tagged and saved for more thorough perusal. Ultimately, 40 papers were selected for review after applying the pre-specified inclusion criteria Results : The worldwide prevalence of PD varies widely. One reason for the variation in prevalence estimates could be due to the differences in survival across countries. The use of epidemiological studies using medical records could be another reason for the variation in disease frequency. Conclusion : PD is common in the elderly. A number of descriptive epidemiologic studies have been conducted worldwide. Comparing the incidence and prevalence of Parkinson’s disease is difficult. Keywords : Parkinson’s disease, Parkinsonism, Epidemiology, Prevalence, Incidence

A systematic review of the worldwide prevalence and incidence of Parkinson's disease.

As demonstrated by the United Nations High-Level Meeting on tuberculosis (TB) held in September 2018, the political momentum for TB has been increasing. The aim of this study was to analyze the current challenges and opportunities for global TB control and, with specific focus on policies surrounding TB control, to reveal what kinds of efforts are needed to accelerate global TB control. We organized two expert meetings with the purposes of assessing the current situation and analyzing challenges regarding TB control. By applying Shiffman and Smith’s framework which contains four categories; Actor, Ideas, Political context, and Issue characteristics, we analyzed the challenges and opportunities for global TB control based on the findings from the two expert meetings. In the Actor Category, we found that although there has already been active engagement by non-governmental organizations (NGOs), civil society organizations (CSOs) and private sectors, there still remained an area with room for improvement. In particular, the complexities behind varying drug regulatory and procurement systems per country hindered the active participation of the private sector in this area. As for the Ideas category, due to an increasing threat of antimicrobial resistance and growing number of global migrations, TB is now widely recognized as a health security issue rather than a purely health issue. This makes TB an easier target for political attention. As for the Political category, having the UN High-Level Meeting itself is not enough; such meetings must be followed up by actual commitments from heads of states. Lastly the issue characteristic indicates that the amount of funding for R&D for new drugs, vaccines and diagnostics for TB is not at an adequate level, and investment in childhood TB and missing cases are particularly in need. This study provides important insight into the current status of global efforts toward end TB epidemic. The outcomes from the UN high-level meeting on TB need to be closely monitored will be crucial for the progress towards this goal.

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Hiroyuki Hori

Papers

Systematic Review of the Prevalence and Incidence of Parkinson's Disease in Asia

A systematic review of the worldwide prevalence and incidence of Parkinson's disease.

Challenges and opportunities for eliminating tuberculosis - leveraging political momentum of the UN high-level meeting on tuberculosis.