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Jul 05 / Springer Healthcare

EAN 2021 In-depth report: Dementia


This EAN 2021 report gives an overview of emerging and future diagnostics in Alzheimer’s disease and dementia.

The European Academy of Neurology

EAN 2021 Virtual Meeting

June 19th – 22nd, 2021

In-Depth Report

The 7th Annual Meeting of the European Academy of Neurology (EAN) - the largest neurology congress in Europe - was held virtually between the 19th and 22nd June 2021 and drew over 11,000 participants. The overarching theme of this year’s congress was ‘Towards Precision Neurology’, reflecting a focus on current and future use of precise tools such as genetics, imaging and omics for the diagnosis and personalised treatment of neurological disorders.

Opening Plenary

EAN President Claudio Bassetti, Bern, Switzerland, began the opening plenary session by reviewing key activities and future initiatives across the EAN’s four main pillars - science, education, membership and advocacy/communication. The vision of EAN is to be the home and voice of neurology in Europe, with a mission to reduce the overall burden of brain diseases. The ‘Big 6’ is a new EAN theme focused on key steps for the promotion/preservation of brain health and prevention of neurological diseases.

Six key steps for the promotion and preservation of brain health

The 'Big 6' is a new EAN theme

“The spread of COVID-19 has not only profoundly changed our lives and habits but has also pushed us to discover innovative ways of working and interacting, while also stimulating a great amount of scientific activity.”

Raphaela Goldbach-Mansky, Bethesda, MD, USA

The opening lecture of EAN 2021 was delivered by Juergen Knoblich, Vienna, Austria, and explored insights from the laboratory that may profoundly influence how neurology research is conducted in the future. To combat the difficulties of murine modelling, cerebral organoids have been developed which can be used to model human brain development and recapitulate neurodevelopmental disorders in stem cell derived 3D cultures.

“The human brain is the most complex and most fascinating organ that mother nature has created - but this complexity comes at a price as the brain is also home to some of the most devastating disorders.”

Juergen Knoblich, Vienna, Austria


Emerging and future diagnostics in Alzheimer’s disease and dementia

Stephane Epelbaum, Paris, France, proposed a future diagnostic pathway for Alzheimer’s disease (AD) in which patients are closely monitored at home using digital biomarkers, thereby providing an enriched population for GP screening using blood-based risk biomarkers such as amyloid-β-1-42/amyloid-β-40. Subsequent specialist cognitive evaluation should include subjective memory complaint, which is a robust indicator of dementia risk. In addition to positron emission tomography (PET) and CSF biomarkers, Dr Epelbaum recommended electroencephalogram (EEG) as a key diagnostic tool which has proved strongly predictive of neurodegeneration in preclinical AD and benefits from being cheap, non-invasive and reproducible.

Femke Bouwman, Amsterdam, the Netherlands, explained how, due to advances in technology, it is now possible to detect the presence of AD pathology in the plasma with good accuracy. A panel of plasma biomarkers can achieve good approximation to the accuracy of cerebrospinal fluid (CSF) biomarkers and benefits from being more patient-friendly than a lumbar puncture or time consuming PET scan. In the future, plasma biomarkers may be used to pinpoint individual patients for RCTs of anti-amyloid or other therapies, or to select patients from memory clinic cohorts who require additional biomarker evaluation.

4 plasma biomarkers in AD

Plasma biomarkers in AD

“In the far future we may use plasma biomarkers to screen the general population for AD”

Femke Bouwman, Amsterdam, the Netherlands

40 risk-factor genes for AD have now been identified

The number of risk-factor genes for AD that have now been identified

Familial dementias are rare but important disorders with risks related to age, family history and phenotype, said Jonathon Schott, London, UK. Gene panels combined with specific testing for repeat disorders have helped to revolutionise diagnosis, but a careful approach must be taken to counselling, testing and interpretation of results. None of the numerous AD risk-factor genes identified are more influential than apolipoprotein E (APOE), explained Dr Schott, but together they provide valuable insights into disease pathogenesis. Moving forward, the advent of polygenic risk scores may find utility for preclinical screening.

CNS neuropathology of dementias: diagnosis at the microscope

The advent of new imaging technologies which allow in vivo visualisation of CNS pathology marks a new frontier in the diagnosis of misfolded pathogenic proteins. This teaching course explored microscopic neuropathology in neurodegenerative diseases, with a focus on dementias due to amyloid, tau, TDP-43 and α-synuclein proteins.

Multiple pathologies in the elderly brain
Multiple pathologies in the elderly brain

Multiple pathologies are seen in the brains of most elderly people

Dietmar Thal, Leuven, Belgium, described how, in addition to the AD pathogenic proteins Amyloid-β and tau, multiple pathologies are seen in the brains of most elderly people including: atherosclerosis of the circle of Willis, small vessel disease, granulovacuolar degeneration and limbic-predominant age-related TDP-43 encephalopathy (LATE). These pathologies can stand alone and/or exhibit complex additive and interactive features. In most cases, therefore, dementia or other types of neurodegeneration do not arise from a single disorder but are the net result of multiple pathologies. Diagnosis should include all underlying pathologies, stressed Dr Thal, and combined treatment strategies may be beneficial, even incorporating therapies which lack standalone efficacy.

“AD has multiple types and is not purely linked to amyloid-β and tau. Copathologies may have an important impact on therapeutic trial outcomes when testing AD-targeting drugs.”

Dietmar Thal, Leuven, Belgium

Tauopathy was reviewed by Gabor Kovacs, Toronto, Canada, who explained that the folding of tau filaments is different in distinct major tau proteinopathies and thought to be a driving force of different morphologies and patterns seen at the microscope.

Sequential/hierarchical involvement of anatomical regions of the brain is evident in major tau proteinopathies, supporting the notion of a preclinical phase that could potentially be targeted for preventative intervention if a suitable biomarker can be identified. Due to the diversity in clinical and cellular types, developing of staging for neuropathology diagnostics is challenging. However, glial tau accumulation appears critical for differential diagnosis. Moving forward, study of a wide range of disorders is needed to provide greater insight into the pathogenesis of tauopathies. Evidence already exists to support the concept that cognitive decline and neurodegeneration in AD is primarily driven by the onset and spread of tau pathology.

The many faces of the TDP-43 protein were explored by Marta Scarioni, Amsterdam, the Netherlands. She explained that frontal temporal dementia (FTD) is both clinically and pathologically heterogenous and definitive diagnosis is only possible through pathology. The neuropathology of FTD is an advancing field, with classification having evolved from ubiquitin to TDP-43. Distinct TDP-43 subtypes have now been delineated that show association with both disease course and disease features. The key clinical indicators pointing to underlying TDP pathology include motor neuron symptoms and psychoses.

Ultimately, the staging of all synucleinopathies is based on anatomical distribution and amount of α-synuclein immunostaining in the brain, explained Steve Gentleman, London, UK. Some clear clinicopathological correlations exist between α-synuclein pathology spread and the appearance of symptoms. However, in the elderly age group, it is important to bear in mind that mixed pathologies often underlie cognitive decline and there are very few cases of pure α-synucleinopathy.

Precision neurology

As part of the Precision Neurology plenary symposium at this year’s EAN, Henrik Zetterberg, Gothenburg, Sweden, discussed current and future use of precise fluid biomarkers for personalised diagnosis and prognosis. In the field of neurodegeneration, encouraging results have been achieved using plasma amyloid-β as a biomarker for plaque pathology, although plasma total-tau based has proved less successful based on current assays. Dr Zetterberg described the data for plasma P-tau181 and P-tau217 as ‘very promising’, providing potential predictive markers of AD-type tangle pathology and neuronal response to amyloid markers. Plasma and serum neurofilament light (NfL) have also emerged as important biomarkers for neurodegeneration.

“We now have the possibility of using simple blood tests to classify according to the ATN scheme which we hope will be useful in clinical trials and practice.”

Henrik Zetterberg, Gothenburg, Sweden

Congress highlights in neurodegenerative disorders
5 congress highlights in neurodegenerative disorders

Congress highlights in neurodegenerative disorders

“In 2021 the FDA approved a drug against AD - aducanumab. This is obviously a seismic event for our field, however, at present no one knows how this will turn out in Europe and we have to wait for the decision of the EMA which is expected in the upcoming year.”

Elisabeth Stogmann, Vienna, Austria


Closing remarks

In closing, Programme Committee Chair, Tony Marson, Liverpool, UK, explained that plans are already well developed for the 8th Annual EAN congress which will take place in Vienna, Austria under the overarching theme ‘Getting Evidence into Practice’. We very much hope this will be an in-person event, stressed Dr Marson but contingency plans are in place for a hybrid congress or reversion to a virtual congress if required.

“The aim for 2022 is to have a congress that represents the whole of Europe with a pan-European flavour. It will be a celebration that we can finally come together again after this really challenging time with the COVID-19 pandemic.”

Tony Marson, Liverpool, UK

©Springer Healthcare 2021. This content has been independently selected and developed by Springer Healthcare and licensed by Roche for Medically. The topics covered are based on therapeutic areas specified by Roche. Inclusion or exclusion of any product does not imply its use is either advocated or rejected. Use of trade names is for product identification only and does not imply endorsement. Opinions expressed do not reflect the views of Springer Healthcare. Springer Healthcare assumes no responsibility for any injury or damage to persons or property arising out of, or related to, any use of the material or to any errors or omissions. Please consult the latest prescribing information from the manufacturer for any products mentioned in this material.