Alzheimer’s disease (AD) is a very common malady of the elderly, currently affecting 5.8 million Americans above the age of 65. It accounts for 60–80% of all dementia cases, which also makes it the most common cause of dementia.1 Its disease pathology initiates around 20 years before the first clinical symptoms,2 and the mechanisms behind the initiation are under constant investigation. Thus, our current understanding of the disease’s onset should already allow for earlier diagnoses and medical intervention – but how is this implemented in common clinical practice?
To discuss this question, Giovanni Frisoni (Department of Psychiatry, Geneva University Hospitals, Switzerland), Wiesje van der Flier (Alzheimer Center Amsterdam, Amsterdam University Medical Center, The Netherlands), Jonathan Schott (National Hospital for Neurology and Neurosurgery, University College London, United Kingdom), and Pierre Krolak-Salmon (Department of Neurology and Geriatrics and Centre Mémoire Ressource et Recherche de Lyon, Hôpital des Charpennes, France) came together on a virtual platform during this year’s virtual EAN.
Cognitive assessment for early differential diagnosis
Cognitive assessment is an essential early diagnosis tool for AD. Prof. van der Flier reminded the audience that “even before the stage of dementia, episodic and working memory, as well as executive function, can be impaired”.3 The identification of several cognitive domains, with the help of various screening tests, enable an early differential diagnosis of AD. Given the current circumstances, Prof. van der Flier pointed out that there is increasing interest in online self-tests as a cognitive screening instrument: “I think future developments will take a flight, especially in this new situation with the COVID-19 and that online testing at home will actually become quite popular in the near future,” she stated at the end of her presentation.
Biomarkers provide evidence
The cognitive impairment in patients with AD is preceded by pathological changes. In the continuum of the disease, amyloid beta (Aß) accumulation and tau-mediated neuronal injury are followed by neurodegeneration, which can be visualised by imaging techniques like magnetic resonance imaging (MRI). Notably, changes that can be detected by MRI are not necessarily specific to AD, and are also present in other neurodegenerative diseases.4 The detection of confirmed biomarkers like Aß or tau via specific amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) analysis allows for a more accurate differential diagnosis.2 “What biomarkers can do is to provide some evidence of the underlying pathology and the underlying cause,” Dr Schott remarked. However, he also pointed out that standardised cut-offs for thresholds are needed to ensure reliable and consistent results in the future.
Are our healthcare systems ready?
“Research in the past decades has shown that we should prevent, rather than cure, AD and dementia by using disease modifying drugs,” Prof. Krolak-Salmon summarised. However, an early diagnosis with the help of cognitive assessment as well as biomarkers is necessary for this approach to be successful. A big constraint is the general lack of specialists, which leads to long waiting times for patients in some countries. In addition, a lack of training and knowledge in primary and specialised care, as well as limited access to diagnostic tools, can lead to fewer early diagnoses.
Currently, according Prof. Krolak-Salmon, the European system is not equipped to diagnose AD early – but this will hopefully change soon. New approaches are impacting the field, including agreements with general practitioner (GP) communities, the implementation of a structured diagnosis strategy, dedicated training of medical professionals and further research on cognitive tools and biomarkers. Hence, earlier diagnosis of AD in the general population is not impossible, but will require the collaboration and efforts of several stakeholders.
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1. Alzheimer’s Association. Alzheimer’s Dement. 2020;16:391–460
2. Clifford RJ, Jr. et al. Alzheimer’s Dement. 2018;14:535–62
3. Cloutier S et al. J Alzheimers Dis. 2020;47:901–13
4. Johnson KA et al. Cold Spring Harb Perspect Med. 2012;2:A006213