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WCN 2015: “Changing Neurology Worldwide” – Santiago, Chile, 31 October– 5 November 2015

7.7 million new dementia cases every year – experts discuss advances in Alzheimer vaccine and biomarkers for early diagnosis

Every four seconds someone in the world comes down with dementia. Dementias are among the main topics under discussion at the World Congress of Neurology currently being held in Santiago de Chile. A vaccination strategy which is just around the corner is among the key advances being presented by experts speaking at the Congress. Speakers are also set to present new data including a new therapeutic monoclonal antibody showing clinical benefit in a first trial, biomarkers for early diagnosis, the role of inflammation in the disease process or Vitamin D deficits and disease progression.

Santiago de Chile, 31 October 2015–Dementias are among the major challenges facing neurology worldwide. According to WHO estimates, 47.5 million people live with dementia worldwide. “Every four seconds, there is a new case, and each year the number of people it affects increases by around 7.7 million according to WHO data,” Roger Rosenberg, Professor of Neurology and Director of the Alzheimer’s Disease Center at the University of Texas Southwestern Medical Center said at the World Congress of Neurology (WCN 2015). About 3,500 participants are gathered in the Chilean capital Santiago for the world's leading neurology event. “Dementia will be the fastest growing health problem over the next few decades.”Alzheimer’s disease (AD) is the leading form of age-related dementia, responsible for 60 to 70 percent of all dementia disorders. It is a progressive and, in regard to clinical scores, a highly variable disease.

Despite being so widespread, dementia is still dismissed as an inevitable symptom of old age in many instances, even among health professionals. This attitude is clearly reflected in a Chilean study presented at the WCN 2015, in which half of the health professionals included in the survey considered their knowledge of dementia to be inadequate. 53 percent of the physicians surveyed had never prescribed symptomatic pharmacological treatment for dementia. “The data shows that dementia is not widely appreciated as a disease with treatable co-morbidities,” Prof Rosenberg commented.

Alzheimer: Vaccination paves the way to effective prevention

A major focus of the WCN in Santiago is on the prevention and early detection of dementia, particularly AD. With AD, many studies around the world focus on the role of the protein amyloid beta and the increased deposition of amyloids in the brain in the genesis and development of the disease. Some of them are leading in the direction of new therapeutic and preventive approaches such as the possible immunisation against beta-amyloid, which is often referred to as the Alzheimer vaccination.

Prof Rosenberg is set to present his own research at the WCN on a vaccination in which DNA encoding the amyloid beta 42 peptide is injected with the gene gun, a method of transferring large molecules such as DNA into the cell. The injected DNA is translated in the vaccinatedperson to produce amyloid beta peptide which in consequence triggers immune responses. “Our research shows the effectiveness, safety and potential therapeutic value of the DNA amyloid beta 42 vaccination in individuals at risk of Alzheimer’s disease,”the expert reported.

There are other promising therapies targeting amyloids, as shown by a new study. “Aducanumab, a monoclonal anti-amyloid antibody, has shown some clinical benefit in a pilot clinical trial presented at WCN. It reduced beta-amyloid plaques and slowed cognitive decline,” Prof Rosenberg commented. “A Phase 3 clinical trial is now being planned.”

Research groups around the world are also making progress as far as a potential delay of onset of dementia disorders is concerned. At the WCN, a team of scientistsfrom the University of Texas is presenting new data on the potential of a specific group of antibodies for this purpose, namely tau oligomer related antibodies. Abnormal levels of tau protein can be found in the brain in a number of neurodegenerative conditions. “Tau oligomer antibodies are being used to identify tau accumulation and may be a means to delay onset of neurodegenerative diseases,” Prof Rosenberg reported. “New research also shows that tau proteins, and in particular the identification of tau stability isoforms and potential isoforms of instability, could also be novel targets for dementia therapy.”

Important role for inflammation, vitamin D supplementation possibly preventive

Other research results being discussed at the WCN concern the identification of factors supporting the development of dementias. Inflammatory processeshave been under investigation for their role in the development of AD pathology. Prof Rosenberg: “According to a study presented by researchers from Brazil, systemic inflammation is correlating with the functional connectivity of the default mode network (DMN) in mild Alzheimer’s disease and mild cognitive impairment (MCI).” The DMNis the network of brain regions that are active when a person is not focused on the outside world and the brain is at wakeful rest.

Mild cognitive impairment is considered a transitional stage of a normal ageing process leading to AD or other forms of dementia. However, not all those affected by MCI go on to develop dementia. “Identifying risk factors forprogressionof MCI would be an important contribution to effective prevention,” Prof Rosenberg says. Vitamin D seems to play an important role in this respect, according to reports from Argentinian researcherspresented at the WCN. “Reduced vitamin D levels increase the risk and development of the disease,” Prof Rosenberg summarises the data. The study authors suggest that a large trial on vitamin D supplementation in patients with MCI should be initiated.

Stroke survivors at risk of dementia

Congress participants also look at the possible interrelation between dementias and other brain conditions. A research team from Turkey is presenting a study at WCN according to which 30 percent of patients are diagnosed with dementia one year after they suffered stroke. “The prevalence of dementia one year after stroke is clearly increased,” Prof Rosenberg underlined.“This might be an indication that vascular and neurodegenerative pathologies interact.”

New therapy targets

In recent dementia research, important progress has been observed in particular in the diagnosis of the disorder. A number of research groups are presenting findings at the WCN on biomarkers for the early diagnosis of the disease in a symptom free or early stage of the disease.

A research team from Lublin, Poland is presenting data which provides new insights into the role of demyelination in Alzheimer’s disease and possible biomarkers for identifying this degenerative process that erodes the myelin sheath protecting the nerve fibres. “The study provides evidence for the significantly increased production of autoantibodies against myelin sheath proteins in AD,” Prof Rosenberg reported. “These antibodies are effective biomarkers of memory loss and AD.”

Epidemiology is another important topic on the Congressagenda. According to the global disease burden data available so far, the prevalence of dementia in some parts of the world, particularly Sub-Saharan Africa and Asia appears to be lower than in Europe or North America. Prof Rosenberg: “At the WCN, a first detailed study on prevalence in Sub-Saharan Africa is being presented that shows the burden of dementia and its implications for African populations.”


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Sources: WCN 2015 Abstract Balthazar et al., Systemic inflammation is linked to default mode network functional connectivity in mild Alzheimer’s disease and mild cognitive impairment; WCN 2015 Abstract Golimstok et al., Vitamin D and progression in mild cognitive impairment (MCI); WCN 2015 Abstract Guerchet et al., Prevalence of dementia in sub-Saharan Africa: systematic review and meta-analysis; WCN 2015 Lasagna-Reeves et al, Targetint tau protein stability in Alzheimer Disease to identify novel therapeutic entry points; WCN 2015 Abstract Logroscino, Dementias across continents: The Global Burden of Disease Study; WCN 2015 Abstract Olavarria et al., Chilean health professionals’ perception of knowledge about dementia; WCN 2015 Abstract Papuc et al., Antibodies against glial derived antigens as early biomarkers of hypocampal demyelination and memory loss; WCN 2015 Abstract Rakez et al., Tau oligomers as a therapeutic target for Alzheimer’s disease; WCN 2015 Abstract Rosenberg and Lambracht-Washington,DNA AB 42 vaccination as therapy to prevent Alzheimer’s disease; WCN 2015 Abstract Sevigny et al., Randomized, placebo-controlled phase 1B study of anti-beta amyloid aducanumab (BIIB037) in prodromal AD/mild dementia: interim results by patient subgroup; WCN 2015 Abstract Tamam and Tamam, Prevalence of dementia one year after stroke.