Biomarker-based diagnosis of mild cognitive impairment due to Alzheimer’s disease: how and what to tell. A kickstart to an ethical discussion

Abstract

New criteria for the diagnosis of Alzheimer’s disease (AD) based on biomarker results have recently been developed and are currently undergoing extensive validation. The next few years may represent a time window where the diagnostic validity of biomarkers will be studied in highly specialized research settings. Biomarkers results will be used to direct clinical diagnosis and, whenever appropriate, therapy and management. This piece aims to stimulate discussion by identifying the ethical challenges involved in the use of biomarkers to make a diagnosis of mild cognitive impairment due to AD and disclose it to patients. At the individual level, these challenges are related to (i) the ethical appropriateness of implementing an ecological diagnostic research protocol, (ii) the related informed consent process, and (iii) the diagnostic disclosure. We justify the ethical legitimacy of implementing a research diagnostic protocol by referring to the respect of patients’ subjectivity and autonomy, and we suggest guidelines for informed consent development and diagnostic disclosure. All of the above points are discussed in light of the unique features of AD, currently scanty treatment options, and knowledge and uncertainties regarding the diagnostic value of biomarkers.

Amnestic MCI patients’ experiences after disclosure of their amyloid PET result in a research context

“…These questions relate, among others, to the prediction of the individual timeline of cognitive decline and the psychological consequences of amyloid PET disclosure [ 6 – 9 ]. There is also limited knowledge on how to best disclose amyloid PET scan results to the tested individual [ 7 , 10 – 12 ].…”

The biomarker-based diagnosis of Alzheimer's disease. 1—ethical and societal issues

“…Of note is that at the present state of knowledge, both the offering and not offering the opportunity to take part in a research protocol in order to improve clinical diagnosis carries ethical implications. The main ethical justification for offering participation in a diagnostic research protocol consists of the basic principle that considers individuals as autonomous persons entitled to ask, to know, and to make present and future decisions about their health and life outcomes (Porteri and Frisoni, 2014). Interestingly, preliminary study results show how highly motivated persons with memory impairments and their caregivers are in obtaining unambiguous diagnosis, at the point that one of their primary reasons to participate in a hypothetical drug clinical trial would be to have access to pre-trial screening that would identify whether the person's memory problems had an underlying AD pathology (Lawrence et al, 2014).…”

From information to follow‐up: Ethical recommendations to facilitate the disclosure of amyloid PET scan results in a research setting

“…Disclosure of results is associated with multiple ethical challenges. Based on the article of Porteri et al [12] that describes multiple important aspects of the informed consent process, we suggest a six-step recommendation to facilitate disclosure and to minimize possible risks of amyloid PET disclosure. This recommendation results in six concrete steps: Information (I), Decision (D), Testing (T), Confirmation (C), Return of result (R), and Postguidance (P).…”

“…Before testing, it is of key importance to provide accurate, clear, and easily understandable information to the participant [10] , [12] , [19] . Participants with diverse educational backgrounds might have difficulties to understand the complexity of the research design and the type of individual research result they may opt for [1] , [20] , [21] .…”

“…The recommendations from Porteri et al, Lingler et al, and Grill et al focus on mild cognitive impairment (MCI) patients, whereas the recommendations by Harkins et al targeted the disclosure of results to cognitively normal adults [10] , [11] , [12] , [13] . Three of four recommendations [10] , [11] , [13] focused on the disclosure of amyloid PET results, whereas one recommendation [12] pertains to biomarker-based information more generally. Relatively few empirical studies have explored the viewpoints of patients, carers, and stakeholders regarding amyloid PET disclosure [14] , [15] , [16] , [17] .…”