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ImportanceSince 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations.ObjectiveTo consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states.Evidence ReviewPubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms “biomarker” OR “amyloid” OR “tau” OR “neurodegeneration” OR “preclinical” OR “CSF” OR “PET” OR “plasma” AND “Alzheimer’s disease.” The references of relevant articles were also searched.FindingsIn the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease.Conclusions and RelevanceThe ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.
ImportanceSince 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations.ObjectiveTo consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states.Evidence ReviewPubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms “biomarker” OR “amyloid” OR “tau” OR “neurodegeneration” OR “preclinical” OR “CSF” OR “PET” OR “plasma” AND “Alzheimer’s disease.” The references of relevant articles were also searched.FindingsIn the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease.Conclusions and RelevanceThe ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.
INTRODUCTIONUnderstanding the impact of biomarker‐based dementia risk estimation in people with mild cognitive impairment (MCI) and their care partners is critical for patient care.METHODSMCI patients and study partners were counseled on Alzheimer's disease (AD) biomarker and dementia risk was disclosed. Data on mood, quality of life (QoL), and satisfaction with life (SwL) were obtained 1 week and 3 months after disclosure.RESULTSSeventy‐six dyads were enrolled, and two‐thirds of the patients opted for biomarker testing. None of the participants experienced clinically relevant depression or anxiety after disclosure. All dyads reported moderate to high QoL and SwL throughout the study. Patients reported more subthreshold depressive symptoms 1 week and lower QoL and SwL 3 months after disclosure. In patients, depression (odds ratio [OR]: 0.76) and anxiety (OR: 0.81) were significant predictors for the decision against biomarker testing.DISCUSSIONNo major psychological harm is to be expected in MCI patients and care partners after dementia risk disclosure.TRIAL REGISTRATIONThis study is registered in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS): http://www.drks.de/DRKS00011155, DRKS registration number: DRKS00011155, date of registration: 18.08.2017.Highlights Patients with mild cognitive impairment (MCI) and study partners were counseled on Alzheimer's disease (AD) biomarker‐based dementia risk estimation. About two‐thirds of patients opted for biomarker testing and received their dementia risk based on their AD biomarker status. Patients who decided in favor or against CSF biomarker testing differed in psychological features. We did not observe major psychological harm after the dementia risk disclosure. Coping strategies were associated with better subsequent mood and well‐being in all participants.
New possibilities of biomarker‐based predictive technologies for Alzheimer's disease (AD) have become more reliable as well as more accessible. Standardized clinical recommendations and guidance for counseling and disclosure in this context are not yet well developed. Our scoping review identified publications from database searches in PubMed, PsycINFO, LIVIVO, and Web of Science. Inclusion criteria were: (1) information or counseling, (2) biomarkers and a type of cognitive impairment or AD, and (3) published between 2005 and 2024. We identified 63 articles and synthesized them along the categories of staged information provision: pre‐test counseling, disclosure, and post‐disclosure follow‐up. Most publications referred to the context of disclosure (48), followed by pre‐test counseling (33), and post‐disclosure follow‐up (31). Some publications referred to all stages of counseling (17). Our findings highlight the need to further develop and specify comprehensive and standardized guidelines for counseling, disclosure, and post‐disclosure follow‐up in the context of AD biomarker testing.Highlights New possibilities of biomarker‐based predictive technologies for Alzheimer's disease (AD) have become more reliable and also more accessible. However, clinical recommendations and guidance for counseling and disclosure in the context of AD biomarker testing are currently not well developed. We carried out a scoping review with the aim to generate an overview of the scientific literature and guidance available regarding counseling, biomarker test result and dementia risk disclosure, and clinical management prior to and in the course of a biomarker‐based diagnosis in early stages of AD. We identified 63 relevant articles. Most publications referred to the context of disclosure (48), followed by pre‐test counseling (33), and post‐disclosure follow‐up (31). Some publications referred to all stages of counseling (17). Our findings highlight the urgent need for national and international consensus guidelines for comprehensive and staged counseling and disclosure practices. While most publications identify relevant ethical challenges posed for counseling practices in the context of AD biomarker testing, they rarely present any practical recommendations for clinicians, on how and what to counsel on a concrete level.
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