Considerations regarding a diagnosis of Alzheimer’s disease before dementia: a systematic review

Jetske van der Schaar, Leonie N. C. Visser, Femke H. Bouwman, Johannes C. F. Ket, Philip Scheltens, Annelien L. Bredenoord, Wiesje M. van der Flier

    Research output: Contribution to JournalReview articleAcademicpeer-review

    Abstract

    Background: The NIA-AA research framework proposes a purely biological definition of Alzheimer’s disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia. Methods: A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer’s disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis. Results: We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects. Conclusions: We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.
    Original languageEnglish
    Article number31
    JournalAlzheimer's Research and Therapy
    Volume14
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2022

    Funding

    Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. WMvdF holds the Pasman Chair. JvdS is appointed at ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. PS is a recipient of JPND-funded EURO-FINGERS (ZonMW-Memorabel #733051102). JvdS wrote a book for a layman’s audience about the personal impact of dominantly inherited Alzheimer’s disease, for which she received grants or contracts from Aegon Nederland and Alzheimer Nederland and royalties from Uitgeverij Prometheus. She received compensation for writings, presentations, or educational events on this topic from Zin Magazine, Psychologie Magazine, Libelle, NRC Media, Provincie Drenthe, Radboud UMC, and Roche NL. She is a member of the advisory board for the National Dementia Strategy of the Dutch Ministry of Health, Welfare and Sport. All payments are made to her. LNCV is supported by a fellowship grant received from Alzheimer Nederland (WE.15-2019-05). She received a small fee for the development of an online course on shared decision-making by EACH, the international organization for research in healthcare. Payments were made to her institution. FHB received grants, contracts, or consulting fees from Optina Diagnostics (Canada), Biogen, and Roche. Payments were made to her institution. PS has received consultancy fees (paid to the institution) from AC Immune, Alkermes, Alnylam, Alzheon, Anavex, Axoltis, Brainstorm Cell, Cortexyme, Denali, EIP, ImmunoBrain Checkpoint, GemVax, Genentech, Green Valley, Novartis, Novo Nordisk, PeopleBio, Renew LLC, and Roche. He received payment or honoraria from Nutricia. He is PI of studies with AC Immune, CogRx, FUJI-film/Toyama, IONIS, UCB, and Vivoryon. He is a part-time employee of Life Sciences Partners Amsterdam. He serves on the board of Brain Research Center and New Amsterdam Pharma. He participated on a Data Safety Monitoring Board or Advisory Board at Genentech. He is a member of the advisory board for the National Dementia Strategy of the Dutch Ministry of Health, Welfare and Sport (paid to the institution). He is co-editor-in-chief of the Alzheimer’s Research and Therapy and was firewalled from the review and decision process. ALB received grants or contracts (paid to her institution) from Horizon2020 INKplant: “Ink-based hybrid multi-material fabrication of next generation implants” (2021-2025); COGEM (RIVM Committee on Genetic Modification) Grant: “The role and meaning of the concept ‘naturalness’ in scientific, legal and societal context” (2019-2021); Netherlands Organisation for Scientific Research (NWO) Crossover Grant: “INTENSE: Innovative Neurotechnology for Society” (2020-2025); Netherlands Organisation for Scientific Research (NWO): “RAIDIO: Responsible Artificial Intelligence for Clinical Decision-Making” (2020-2025); EU H2020 grant “EXPANSE: exposome empowered tools for healthy living in urban settings” (2020-2024); National Science Agenda (NWA): SYMPHONY: Orchestrating personalised treatment in patients with a bleeding disorder (2019–2023); Horizon2020 grant “iPSpine: induced pluripotent stem cell-based therapy for spinal regeneration” (2019–2024). She is a member of Dutch Senate (payment to her), Board of ZonMw (payment to her institution), Supervisory Board Amsterdam UMC (payment to her) International Society for Stem Cell Research Ethics Committee (no payment), and IQVIA’s Ethics Advisory Panel (payment to her institution). Research programs of WMvdF have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, and Combinostics. She holds the Pasman chair. She is a consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. She participated in an advisory board of Biogen MA Inc. She is an associate editor at Brain. All funding is paid to her institution.

    FundersFunder number
    COGEM2019-2021
    EU-FP7
    EU-JPND
    Edwin Bouw Fonds and Gieskes-Strijbisfonds
    Horizon2020
    National Science Agenda
    Responsible Artificial Intelligence for Clinical Decision-Making
    Roche
    Northwest Airlines
    Horizon 2020 Framework Programme2020-2024
    ZonMw
    Nederlandse Organisatie voor Wetenschappelijk Onderzoek2020-2025

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