With great interest, we read the letter to the editor by Perrin et al. in response to our recent manuscript “General practitioners' perspectives on Alzheimer's disease blood biomarkers”.1 Both studies highlight similar perspectives from European general practitioners (GPs) regarding the use and implementation of Alzheimer's disease (AD) blood biomarkers in primary care. GPs see potential benefits in using AD blood biomarkers, but they also perceive challenges concerning disclosure and interpretation of these biomarkers and patient management post-diagnosis. Although they shared optimism about the availability of an accessible, timely and non-invasive AD diagnosis, concerns arose respecting AD overdiagnosis, being faced with inappropriate testing demands and imposing unwarranted psychological burden on patients. These concerns resulted in GPs feeling uncomfortable with assuming full responsibility for AD diagnosis and disclosure of AD blood biomarker results. Further research into GPs’ perspectives is important to provide a more in-depth overview and determine the relative importance of factors associated with the use and implementation of AD blood biomarkers in primary care. However, these two studies, together with the research of Burns and O'Brien and other developments in the field, may already allow some preliminary conclusions about the road forward.2, 3 Taken together, they illustrate the need for a careful and interdisciplinary approach regarding future implementation of AD blood biomarkers in primary care. The first evidence concerning the accuracy of AD blood biomarkers in primary care allows for optimism towards their diagnostic value, but these results need additional validation.4 In addition, there is a lower prevalence of AD in primary care than in secondary or tertiary care. This leads to a lower pre-test probability, lowering the risk of false-negative results while increasing the risk of false-positive results.5 Thus, a two-tiered approach may be needed to increase the chance of accurately identifying AD cases. For example, by adding brief pen-and-paper or digital cognitive tests to any diagnostic work-up that includes AD blood biomarkers.6, 7 In a scenario where disease-modifying therapies (DMTs) are available, a confirmatory test later in the diagnostic work-up is likely to remain necessary.8 Furthermore, evidence-based (counseling) guidelines and collaboration between primary, secondary, and tertiary care are needed to overcome the challenges described. Additionally, education about AD blood biomarkers through training or toolkits could help to mitigate GPs’ concerns.9 Importantly, AD blood biomarkers should always be interpreted in conjunction with a patient's clinical presentation.1 Both studies showed that availability of AD treatment is likely to change GPs’ perspectives toward AD blood biomarkers. With the recent approval of the first DMTs by the European Medicines Agency, there is a clear imperative to initiate preparations for a future in which AD blood biomarkers play a clearly defined role in selecting eligible patients for DMTs. The next step is to increase the willingness of GPs to use AD blood biomarkers by taking the considerations outlined above into account. L.N.C. Visser has received funds from ZonMW, Alzheimer Nederland, Health∼Holland Topsector Life Sciences #LSHM20106). Research of C.E. Teunissen is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE) and No 101119596 (TAME), Innovative Medicines Initiatives 3TR (Horizon 2020, grant no 831434) EPND (IMI 2 Joint Undertaking (JU), grant No. 101034344) and JPND (bPRIDE, CCAD), European Partnership on Metrology, co-financed from the European Union's Horizon Europe Research and Innovation Programme and by the Participating States (22HLT07 NEuroBioStand), Horizon Europe (PREDICTFTD, 101156175), CANTATE project funded by the Alzheimer Drug Discovery Foundation, Alzheimer Association, Michael J Fox Foundation, Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands. C.E. Teunissen is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences #LSHM20106). C.E. Teunissen is recipient of TAP-dementia, a ZonMw funded project (#10510032120003) in the context of the Dutch National Dementia Strategy. C.E. Teunissen has research contracts with Acumen, ADx Neurosciences, AC-Immune, Alamar, Aribio, Axon Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Instant Nano Biosensors, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama, Vivoryon. C.E. Teunnisen has research contracts with Acumen, ADx Neurosciences, AC-Immune, Alamar, Aribio, Axon Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, C2N diagnostics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Instant Nano Biosensors, Merck, Muna, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama, Vaccinex, Vivoryon. She is editor in chief of Alzheimer Research and Therapy, and serves on editorial boards of Molecular Neurodegeneration, Alzheimer's & Dementia, Neurology: Neuroimmunology & Neuroinflammation, Medidact Neurologie/Springer, and is committee member to define guidelines for Cognitive disturbances, and one for acute Neurology in the Netherlands. She has consultancy/speaker contracts for Aribio, Biogen, Beckman-Coulter, Cognition Therapeutics, Eisai, Eli Lilly, Merck, Novo Nordisk, Novartis, Olink, Roche, Sanofi and Veravas. A.C. van Harten has received funding from ZonMW and Alzheimer Nederland (WE.06-2021-06) and has received consulting fees from Lilly. Thomas Claessen has no disclosures. Author disclosures are available in the Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Claessen et al. (Thu,) studied this question.