Alzheimer’s disease and other dementias will double over the next thirty years

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Over the past three decades, a number of significant pieces of work have been undertaken to estimate the prevalence of dementia at a European level, including:

  • EURODEM study in the early 80s (updated in 2000)
  • Alzheimer Europe’s project European Collaboration on Dementia – EuroCoDe (2006-2008)
  • ALCOVE, the 1st EU Joint Action on Dementia (2011-2013).

As the most recent of these studies is six years old, Alzheimer Europe recognised the importance of establishing more recent dementia prevalence estimates, using the most up-to-date academic literature on the subject.

The findings presented below are based on a collaborative analysis of prevalence studies published since the conclusion of the EuroCoDe project.

A total of 16 studies meeting predefined quality criteria were included in the collaborative analysis.

The key findings of this new Alzheimer Europe report include:

  • For men, there has been a reduction in the prevalence of dementia across all age groups over the past ten years when compared to Alzheimer Europe’s 2008 EuroCoDe estimates.
  • For women, apart from the age group of women between 75 and 79 years, there has been a reduction in the prevalence of dementia over the past ten years when compared to EuroCoDe.
  • The number of people living with dementia in the European Union (EU27) is estimated to be 7,853,705 and in European countries represented by AE members, 9,780,678. Compared to its earlier estimates, this constitutes a significant reduction from 8,785,645 for the EU27 and from 10,935,444 for the broader European region.
  • Women continue to be disproportionately affected by dementia with 6,650,228 women and 3,130,449 men living with dementia in Europe.
  • The number of people with dementia in Europe will almost double by 2050, increasing to 14,298,671 in the European Union and 18,846,286 in the wider European region.

Women continue to be disproportionately affected by dementia with 6,650,228 women and 3,130,449 men living with dementia in Europe.

Alzheimer Europe’s Yearbook also highlighted significant limitations in the available research into dementia prevalence and a lack of research into:

  • the prevalence of younger people with dementia (i.e. those aged under 65)
  • the prevalence of different types of dementia
  • the number of people affected by different stages of dementia including mild cognitive impairment
  • the prevalence of dementia of people from ethnic minority groups.

Commenting on the findings, Alzheimer Europe Executive Director, Jean Georges, said:

“It is promising to see that healthier lifestyles, better education and improved control of cardiovascular risk factors seem to have contributed to a reduction of the prevalence of dementia.

However, our report also demonstrates that the number of people living with the condition is set to increase substantially in the years ahead, which will only place greater pressure on care and support services unless better ways of treating and preventing dementia are identified.

If people with dementia, their families and carers are to receive the high-quality and person-centred care they need, governments must ensure their health and care systems are ready to meet this demand and greater investments in research into the treatment and prevention of dementia are needed.”

Source:
Alzheimer’s Europe


Alzheimer’s disease (AD) isa neuropathological disease involving progressive neurodegeneration.

It initially impacts memory and leads to progressive and irreversible cognitive decline and functional impairment.

In 2010, an estimated 503,400 deaths of Americans aged 75 years and older were attributed to AD (James et al., 2014). In Europe, a meta-analysis estimated the prevalence and incidence of AD in Europe to be 5.05% and 11.08 per 1,000 person-years, respectively (Niu et al., 2017). With increasing average life expectancy, AD is predicted to become a major socioeconomic burden in the near future and is projected to affect 131.5 million people worldwide by 2050 (Khan et al., 2017).

Despite advancements in understanding AD, its exact etiology and pathogenesis remain unclear. Over the past three decades, our understanding of the mechanism of AD has increased and methods for the diagnosis and treatment of AD have been developed. Simultaneously, scientific and technological strength has developed in China. However, global and China-specific trends in AD research have not yet been described.

Bibliometrics, an emerging field of information science, is useful for gaining insights into the intellectual structure of an academic field. Bibliometric studies can identify hotspots in a specific research area.

In addition, bibliometric analyses are often used to identify academically significant articles and landmark publications.

Bibliometric analyses have been previously used to investigate the research output of various fields at the global, regional, and national levels, including neoplasms (Iqbal et al., 2019), parasite (Goarant et al., 2019), pituitary adenoma (Guo et al., 2018), and glioma (Burak Atci et al., 2019). However, a bibliometric study has not yet been conducted to understand the landscape of AD.

To evaluate the quantity and influence of global AD research, a bibliometric analysis was performed over the time period of 1988 to 2017. The present state and progress of AD research was examined both globally and in China.

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Alzheimer’s disease (AD)-related articles globally and in China. (A) Global number of AD-related publications. Blue bars indicate the quantity of AD articles. (B) Sum of AD-related articles from the top 20 countries and territories. (C) AD articles published from the top six countries over time. (D) Heat map showing the distribution of AD publications in China.

Discussion

The present study provides a comprehensive overview of the global development of AD research and summarizes the contribution of China to AD research over the last three decades. In the past 30 years, the global volume of AD research has increased tremendously. A linear growth was observed in the number of AD publications over the survey period, consistent with publications in other neuroscience research fields (Yeung et al., 2017a).

Most research originated in the United States, highlighting that country’s important role in AD research. Our findings suggest that healthcare expenditures are substantially related to the economic power of a country.

With its rapid growth in science and technology, China has made great strides and now holds a respectable position in AD research among developing countries, but a gap still exists between China and developed countries in terms of the academic level of AD research.

In recent years, especially since 2008, the Chinese government has supported the development of AD research: the number of projects funded by NSFC has increased, and the amount of funding from the NSFC has expanded. At the same time, the lens of TCM has been used to investigate the pathological mechanisms and prevention of AD.

Global AD research has developed appreciably, with 481 articles published in 1988 and 14,985 in 2017. Based on results of these studies, the pathological mechanisms of AD are becoming more and more defined, including the accumulation of pathological misfolded tau (Leuzy et al., 2019), the amyloid-β cascade hypothesis (Panza et al., 2019), circadian dysrhythmia (Van Erum et al., 2018), gut microbiota (Jiang et al., 2017), cholinergic neuron death and acetylcholine deficiency (Anand et al., 2012), and chronic inflammation and oxidative stress (Jaworski et al., 2011).

In line with the mechanisms mentioned above, drugs to treat AD have been developed to reduce tau protein abnormalities, inhibit amyloid-β protein production, treat circadian rhythm disorder, modulate the structure and metabolism of gut microbiota, increase acetylcholine synthesis, protect cholinergic neurons, and promote anti-inflammatory and anti-oxidant compounds.

At present, there is no cure for AD; treatments for AD only alleviate disease symptoms, and many treatments are effective in some AD patients for a limited time. Despite research efforts, no disease-modifying treatments are available and the underlying mechanisms of AD and optimal treatment targets have not been fully elucidated.

Early non-invasive examination tools such as transcranial sonography (Favaretto et al., 2018) have been improved, and functional neuroimaging techniques have been gradually applied in AD research (Dennis and Thompson, 2014; delEtoile and Adeli, 2017).

The overarching goals of AD research are to determine when and how interventions can slow or stop cognitive decline in patients, and to identify early signs of decline and treatment response. Phase II results of new treatments and several therapies in phase III clinical trials are encouraging.

Previous studies revealed that pathophysiological changes of AD take place decades before clinical symptoms of dementia appear (Morris, 2005). This extended preclinical phase of AD provides a critical opportunity for disease-modifying agents to halt or slow the progression of AD (Sperling et al., 2011).

We therefore optimistically anticipate more effective therapies in the foreseeable future. Partnerships between pharmacy, biotechnology, physics, chemistry, electronic informatics, botany, and medicine are growing.

These will enable treatments with a range of targets to be developed, with an emphasis on drug repositioning and novel drug discovery. More investment is urgently needed to enable more treatments to be studied in clinical trials.

Some form of preventative treatment strategy, possibly specialized combination therapies with multiple targets, may be available in the next decade.

Research results must be published in the form of journal articles. Globally, 8,935 journals have published AD-related articles, with the 10 journals publishing the largest number of articles in this field contributing only 15.925% of published AD research. Journals publishing large numbers of AD-related articles, such as Neurobiology of Aging, Journal of Alzheimer’s Disease, Neurology, PLoS ONE, Journal of Neurochemistry, and Neuroscience Letters, allow different viewpoints to be freely exchanged.

The journals publishing the 10 most-cited articles and those publishing the largest number of articles are not the same, for complex reasons. The journals publishing the 10 most-cited articles have long histories, such as the Lancet, published since 1823, Nature, published since 1869, Science, published since 1880, and the Journal of Neurology, Neurosurgery, and Psychiatry, published since 1920.

Being published in such well-established journals might have allowed these articles to accumulate a large number of citations, consistent with suggestions from a previous neuroscience study (Yeung et al., 2017b).

By contrast, citations can have a snowball effect, since articles with higher impact factors are likely to be cited more often (Lefaivre et al., 2011; Yeung et al., 2017b). These highly cited articles should be familiar to every AD researcher and are critical for understanding the key messages in this field.

Large clusters in keyword co-occurrence networks indicate important research hotspots. Worldwide, the number of keywords in AD-related literature has grown from 4 in 1988 to 22,641 in 2017, illustrating the enriched content of this research.

Popular research topics include beta-amyloid, tau, aging, the hippocampus, neurodegeneration, apoptosis, neuroprotection, neuroinflammation, and neurodegenerative diseases.

These represent good choices for strong AD research teams but may be risky for less established research teams owing to the difficulty of securing funding and making research breakthroughs in these relatively underdeveloped areas.

Less developed research areas include neuroimaging, functional connectivity, iron, reactive oxygen species, alpha-synuclein, proteostasis, phytochemicals, homocysteine, voxel-based morphometry, angiogenesis, and sleep.

Dynamic research trends can be observed to understand changes in the clustering network and to make informed decisions on research directions. Regardless, each of these areas helps to improve our understanding of the pathophysiological mechanisms of AD.

Despite changes in research topics, the countries and institutes producing the most AD literature did not change significantly between 1988 and 2017. The United States, Canada, Japan, Australia, and European Union countries continue to be major contributors to AD research. Remarkably, these countries were previously identified as major contributors to neuroscience research (Yeung et al., 2017a), indicating that these countries and their institutes occupy core positions in global research.

Prior to 2008, AD research in China was progressing slowly. Since 2008, Chinese AD research has grown substantially. A possible explanation for this is that the Chinese government established the Central Coordination Group for Talents Work and implemented the Recruitment Program of Global Experts in 2008.

By 2018, the program has attracted about 6,000 Chinese scientists, entrepreneurs, and scholars living abroad to return to China. Another possible explanation for this growth is the increased financial aid to AD research and the enhanced funding system for AD research.

Together, these results provide insights into the importance of both talent and financial support for developing scientific research.

The economic power of a country has a direct bearing on its medical research expenditures (Zhang et al., 2017; Ye et al., 2018). In recent years, China’s economic power has grown rapidly and the country has become the world’s second-biggest economy. This could greatly boost AD research in China. The NSFC, with 18 sponsor systems covering all scientific subjects, is a bellwether of scientific research grants in China.

In addition to support for local scientific researchers, the NSFC also provides substantial support to international collaborative projects and Chinese scientists returning from overseas studies. Beyond the China-wide funding system, the country has established a medical research funding system at the provincial, municipal, and district levels, with funds such as the Zhejiang Provincial Natural Science Foundation, and the Qingdao Municipal Source Innovation Project Fund.

Thanks to these policies and funding systems, a large number of outstanding scholars have returned to China and have promoted AD research because of the concepts, techniques, international academic exchanges, and collaborations they bring with them. Additionally, the huge population base in China provides an unparalleled advantage for AD clinical research.

According to data from the Sixth Census of China’s National Bureau of Statistics (2010), 13.26% of China’s population is over 60 years old; according to the Statistical Bulletin of Social Services Development published by the Ministry of Civil Affairs in 2016, 16.7% of China’s population is over 60 years old.

It estimated that, by 2030, the proportion of the total population over 60 years old will exceed 20% of the total population. So far, researchers in China have relatively low output in clinical trials and randomized controlled trials compared to basic research.

This is largely due to the NSFC principally supporting basic scientific research. Clinical study of AD in China has great potential, and platforms for clinical cooperation, databases, and analysis systems should be planned to unite and integrate this massive clinical potential.

However, the gap between China and leading countries in AD research cannot be ignored. While the total number of AD articles from China has increased dramatically in recent years, the citation frequency and h-index remain low.

In terms of research types, Chinese publications are highly focused on basic research, and in earlier years, Chinese AD research lagged behind global AD research. For example, in 1988, no AD-related research was published in China; in 1997, apoptosis and neurodegeneration appeared on global keywords co-occurrence maps, while these keywords only appeared on China’s keywords co-occurrence maps in 2007. Studies associated with MRI and schizophrenia were conducted globally in 2007, but these keywords only appeared in China’s keywords co-occurrence maps in 2017.

Only one Chinese research institute has entered the top 80 global institutions contributing to AD research. In our bibliometric analysis, China’s scientific research institutions impacted the world institutions map only in 2017.

There are few AD-related international journals in China; creation of several international AD-related journals might attract submissions and encourage academic exchange. Finally, TCM research provides a unique opportunity for AD research in China. TCM has been prescribed in the Chinese community for more than 2000 years, and many herbal compounds are regarded as promising anti-AD drugs (Howes et al., 2017).

However, unknown molecular targets and mechanisms, incorrect dosage, and high toxicity of herbal concoctions due to their complex formulations have hindered the therapeutic development of TCM. Chinese researchers could achieve breakthroughs in pharmacological research in TCM, eventually developing TCM as alternative medicines to modulate AD.

The bibliometric analysis had some limitations. First, bibliometric analyses cannot necessarily measure the validity of or the scientific quality of publications and instead must focus on the impact of the research.

A highly cited publication may not necessarily be of high scientific quality. An article’s citation count depends on a variety of factors, including journal type, research model, and self-citing rate. Second, delayed publication collections from the WOS and PubMed databases could also cause bias in the study.

Third, the WOS and PubMed databases mainly included literature written in English, excluding many non-English publications. Fourth, the WOS and PubMed databases classify literature types differently, so the literature identified from different databases cannot be compared mechanically. Readers should note these confounding factors when interpreting the results from the present study.

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