Call to Action: Davos Alzheimer’s Collaborative Calls for the Implementation of Innovative, Global Strategies for Alzheimer’s Accurate Diagnosis.

We are entering a new, critical period for the global response to Alzheimer’s disease with novel treatments and diagnostic tests poised to transform care. However, in order for patients, clinicians, and families to realize the benefits of these innovations, health systems, governments, and other stakeholders must prioritize implementation to speed clinical adoption and broaden access.

On June 18th, the Davos Alzheimer’s Collaborative (DAC) Healthcare System Preparedness Learning Laboratory convened 450+ stakeholders from 45 countries and 270+ organizations to explore the current landscape for clinical adoption of blood biomarkers, introduce DAC Healthcare System Preparedness’s (DAC-SP) newly launched Accurate Diagnosis (AccDx) program, and discuss ongoing collaborations with organizations around the world to speed and scale early detection and accurate diagnosis of Alzheimer’s disease and related dementias.

The discussion featured perspectives from: Karen Blackmon, Imarisha Center for Healthy Brain Aging, Brain and Mind Institute, Aga Khan University; Jeff Burns, University of Kansas Alzheimer’s Disease Research Center; Amy Deckert, Davos Alzheimer’s Collaborative; Ishtar Govia, Amagi Health, Ltd.; Atsushi Iwata, Tokyo Metropolitan Institute for Geriatrics and Gerontology; Tim MacLeod, Davos Alzheimer’s Collaborative; Lefkos Middleton, School of Public Health, Imperial College London; Michelle Mielke, Wake Forest University School of Medicine; Suzanne Schindler, Washington University; and George Vradenburg, Davos Alzheimer’s Collaborative.

As next steps, DAC calls on governments, healthcare systems, global organizations, the private sector, and other stakeholders to implement several key actions:

1 Accelerate clinical adoption of blood biomarker tests and other innovative diagnostic tools. Blood tests for amyloid pathology are now available in multiple countries and hold great promise for early detection and accurate diagnosis. However, there is a need to translate research into pragmatic guidance for healthcare systems and clinicians to determine appropriate tests for their context of use, interpret results, and how to integrate tests into routine clinical practice in real world care settings. The recent CEOi Blood Biomarker Working Group publication in Nature Reviews Neurology represents an important step forward, laying out performance standards to guide health systems as they select and adopt blood tests in the United States.

1 Bridge healthcare system gaps to drive towards accessible, early, and accurate diagnosis. The first-of-its-kind DAC-SP AccDx program recently launched with 8 sites from 5 countries, to adopt innovative blood biomarker tests in the diagnostic pathway. Partners are already working together through a Community of Practice to share learnings and find solutions to common challenges. Findings will be shared at future DAC events, including the Learning Laboratory and build on the DAC-SP Early Detection Blueprint.

1 Prioritize education and support for primary care providers. Clinician education related to new diagnostic screening and tests is essential, especially at the primary care level. Today, the majority of people with cognitive impairment are still not identified, resulting in individuals not having access to critical care and support services in a timely manner. For new tests, primary care providers need help understanding the difference between Alzheimer’s disease and dementia, when to provide the tests, how to interpret and disclose results, what steps to take after diagnosis, and how best to engage with specialists.

2 Advance, fund, and scale global implementation and innovation. Governments, global organizations, and the Alzheimer’s disease community cannot afford to wait on the challenges faced by LMICs, home to the majority of people with dementia. Our collective efforts in high resource settings will help inform infrastructure needs in LMICs. At the same time, innovations from LMICs have the potential to deliver important benefits to the globe, with opportunities of lower costs and greater scalability. DAC-funded programs in Jamaica to identify and address reversible causes of cognitive impairment and research on fluid biomarkers and cognitive assessments in Kenya are part of this journey. Programs such as these should be a policy and funding priority for governments, foundations, multilateral organizations, and others, given the size of the challenge, the immense economic impact, and promising advancements on the horizon.

After decades of effort, we are finally seeing vital new diagnostics and treatments poised to move from the lab to the clinic. Our challenge now is to accelerate this process, far faster than the typical 17-20 years for routine use of clinical innovations, while ensuring new tools are used appropriately for the millions of families affected by Alzheimer’s disease in every country and community around the world.

DAC Healthcare System Preparedness Program will continue collaborating with our partners to advance these goals, share findings through our Learning Laboratory, and equip healthcare systems to implement adaptable, proven solutions.

Ett nytt test, utvecklat av en forskargrupp vid Wolfson Institute of Population Health vid Queen Mary University of London, kan förutsäga demens upp till nio år före en klinisk diagnos. Med >80 % noggrannhet är denna metod ett mer tillförlitligt test för att förutsäga demens än vanliga metoder för demensdiagnostik, såsom minnestester eller mätningar av hjärnans krympning.

A new test, developed bya WIPH-led research team, is able to predict dementia up to nine years before a clinical diagnosis. With >80% accuracy, this method is a more reliable test for predicting dementia than commonly used methods of dementia diagnosis, such as memory tests or measurements of brain shrinkage.

Led by Professor Charles Marshall, the team developed the predictive test by analysing functional MRI (fMRI) scans to detect changes in the brain’s ‘default mode network’ (DMN). The DMN connects regions of the brain to perform specific cognitive functions, and is the first neural network to be affected by Alzheimer’s disease. The researchers used fMR scans from over 1,100 volunteers from the UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from half a million UK participants, to estimate the effective connectivity between ten regions of the brain that constitute the default mode network.

The researchers assigned each patient a probability of dementia value, based on the extent to which their effective connectivity pattern conformed to a pattern that indicates dementia or a control-like pattern. They compared these predictions with the recorded UK Biobank medical data for each patient.

The findings showed that the model accurately predicted onset of dementia up to nine years before an official diagnosis was made, and with greater than 80% accuracy. In the cases where the volunteers had gone on to develop dementia, it was also found that the model could predict, within a two-year margin of error, how long it would take for that diagnosis to be made.

The researchers also examined whether changes to the DMN might be caused by known risk factors for dementia. Their analysis showed that genetic risk for Alzheimer’s disease was strongly associated with connectivity changes in the DMN, supporting the idea that these changes are specific to Alzheimer’s disease. They also found that social isolation was likely to increase risk of dementia through its effect on connectivity in the DMN.

Professor Charles Marshall, who led the research team from the WIPH Centre for Preventive Neurology said: ‘Predicting who is going to get dementia in the future will be vital for developing treatments that can prevent the irreversible loss of brain cells that causes the symptoms of dementia. Although we are getting better at detecting the proteins in the brain that can cause Alzheimer’s disease, many people live for decades with these proteins in their brain without developing symptoms of dementia. We hope that the measure of brain function that we have developed will allow us to be much more precise about whether someone is actually going to develop dementia, and how soon, so that we can identify whether they might benefit from future treatments.’

Samuel Ereira, lead author from the WIPH Centre for Preventive Neurology, said: ‘Using these analysis techniques with large datasets we can identify those at high dementia risk, and also learn which environmental risk factors pushed these people into a high-risk zone. Enormous potential exists to apply these methods to different brain networks and populations, to help us better understand the interplays between environment, neurobiology and illness, both in dementia and possibly other neurodegenerative diseases. fMRI is a non-invasive medical imaging tool, and it takes about 6 minutes to collect the necessary data on an MRI scanner, so it could be integrated into existing diagnostic pathways, particularly where MRI is already used.’

Hojjat Azadbakht, CEO of AINOSTICS (an AI company collaborating with world-leading research teams to develop brain imaging approaches for the early diagnosis of neurological disorders) said: ‘The approach developed has the potential to fill an enormous clinical gap by providing a non-invasive biomarker for dementia. In the study published by the team at QMUL, they were able to identify individuals who would later develop Alzheimer’s disease up to nine years before they received a clinical diagnosis. It is during this pre-symptomatic stage that emerging disease-modifying treatments are likely to offer the most benefit for patients.’

Charles R. Marshall, Sam Ereira, Sheena Wates, Adeel Razi. Early detection of dementia with default-mode network effective connectivity. Published in Nature Mental Health. https://www.nature.com/articles/s44220-024-00259-5

*UKB data access was funded by a grant from the Tom and Sheila Springer Charity.

The Division of Clinical Neuroscience vid Oslo universitetssjukhus och det svenska biofarmabolaget TikoMed har nyligen undertecknat ett forskningssamarbetsavtal. Parterna är överens om att samarbetet ska leda till mer kunskap och bättre behandlingsalternativ för patienter med diagnosen Amyotrofisk lateralskleros – ALS.

TikoMed har tidigare genomfört och rapporterat om två kliniska fas 2a-studier på ALS patienter, en vid Sahlgrenska Universitetssjukhuset i Sverige och en vid University of Birmingham i Storbritannien, båda med lovande resultat.^1,2 Studiedata bekräftar säkerheten och tolerabiliteten för ILB® hos patienter med ALS, samtidigt som de pekar på ILB®s framtida potential som det första sjukdomsmodifierande läkemedlet för behandling av både familjär- och sporadisk ALS med minimala biverkningar.

TikoMeds vetenskapliga rådgivare, professor Ann Logan, hedersprofessor i regenerativ medicin vid University of Warwick, säger: ”Vi är mycket exalterade över den kliniska potentialen för ILB®, en behandling som kan visa sig vara banbrytande för patienter inom flera förödande neurodegenerativa sjukdomar.”

Svensk uppfinnare
TikoMed är ett svenskt, privat företag som grundades 2002 av familjen Bruce. Lars Bruce, som leder ILB® programmet, är entreprenör och uppfinnare med flera kommersiella uppfinningar inom mekanik, metallurgi och medicin. Uppfinnaren Lars Bruce kallar läkemedlet ILB® för upptäckten av «The Missing Link», som orkestrerar kroppens signaler för reparation av vävnader. ILB® aktiverar kroppens naturliga reparationssystem och är ett läkemedel som behandlar neurodegenerativa och neuroinflammatoriska processer genom endogen aktivering av en repertoar av tillväxtfaktorer.

Högspecialiserade Oslo universitetssjukhus
Oslo Universitetssjukhus (OUS) är ett högspecialiserat sjukhus som ansvarar för omfattande regionala och lokala sjukhusuppdrag och som tillhandahåller högkvalitativ service till innevånarna i  Oslo. OUS har också ett rikstäckande ansvar för ett antal nationella och multiregionala kliniska uppdrag och driver även flera nationella kompetenscentrum.

En stor del av den totala medicinska forskningen som bedrivs av norska medicinska centra utförs vid OUS. Detta är ett resultat av OUS allmänna forskningsstrategi och dess omfattande internationella och nationella nätverkssamarbete. https://www.oslo-universitetssykehus.no/en/about-oslo-university-hospital/#research

Publikationer:

1. Logan A, Nagy Z, Barnes NM, Belli A, Di Pietro V, Tavazzi B, Lazzarino G, Lazzarino G, Bruce L, Persson LI. A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for Amyotrophic Lateral Sclerosis. PLoS One. 2022 May 25;17(5):e0267183. doi: 10.1371/journal.pone.0267183. PMID: 35613082; PMCID: PMC9132272.

1. Srinivasan V, Homer V, Barton D, Clutterbuck-James A, Jenkins S, Potter C, Brock K, Logan A, Smith D, Bruce L, Nagy Z, Bach SP. A low molecular weight dextran sulphate, ILB®, for the treatment of Amyotrophic Lateral Sclerosis (ALS): an open-label, single-arm, single-centre, phase II trial. PLoS One. 2024 (in press).

Trots ökade krav på sjukvården från Nato och erfarenheterna från pandemin känner få läkare till om arbetsgivaren har en plan för en akut kris eller krigssituation. Färre än två av tio vet vad de förväntas göra och färre än var tionde har övat. Det visar en ny undersökning från Läkarförbundet.

Vårdens beredskap är allt annat än god. Att alla medarbetare känner till de planer som finns och att de har övat är en grundläggande förutsättning för att sjukvården ska kunna hantera en kris eller krigssituation, säger Sofia Rydgren Stale, ordförande för Läkarförbundet.

Sofia Rydgren Stale, ordförande för Läkarförbundet

Regionerna har viktiga uppgifter inom svensk krisberedskap, då de ansvarar för hälso- och sjukvård. Enligt lag ska de också ha planer för detta. Natomedlemskapet har också ökat kraven på sjukvårdens kapacitet att hantera masskadehändelser.

En ny undersökning från Läkarförbundet visar dock att drygt fyra av tio läkare inte vet om arbetsgivaren har en plan. Två av tio svarar att plan saknas. Många vet inte heller vad de har för uppgift vid en kris. Färre än två av tio vet vad de förväntas göra och färre än var tionde har övat.

Drygt fyra av tio tycker att beredskapen har förbättrats efter Covid-19-pandemin. Samtidigt tycker var tredje att förmågan att hantera akuta kriser och krigssituationer är oförändrad eller försämrad.

– Det är tydligt att vårdens arbetsgivare behöver förbättra beredskapen. Trots erfarenheterna från pandemin i färskt minne saknas rutiner på många håll. Medarbetarna behöver veta vilka uppgifter de ska ha och de behöver få utrymme att öva, säger Sofia Rydgren Stale.

Läkarförbundet arrangerade ett seminarium på årets Almedalsveckan med rubriken ”Vad innebär Natos krav på svensk sjukvård”? Seminariet genomfördes den 26 juni kl. 8:40 – 9:30 och livesändes på Läkarförbundets Facebooksida.

Om undersökningen
Enkäten genomfördes 20-29 maj. 1 650 läkare svarande och svarsfrekvensen är 38 procent. Svaren är viktade för att vara representativa för medlemsgruppen. Läkarförbundet har drygt 58 000 medlemmar.

Sveriges läkarförbund