Amyloid imaging, Risk Disclosure and Alzheimer’s Disease: Ethical and Practical Issues

Roberts, J. Scott; Dunn, Laura B.; Rabinovici, Gil D.

doi:10.2217/nmt.13.25

Cited by 58 publications

(125 citation statements)

References 69 publications

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“…This discussion aims at finding a much-desired balance between the "value of knowing" (23) and the principle of nonmaleficence ("avoiding potential harms of disclosure given the currently unproven clinical utility" (24)). Positive aspects of disclosing the results of amyloid imaging are the possibility of adapting the life plan and keeping autonomy, whereas negative aspects relate to fear of upsetting patients who have no therapeutic options.…”

Section: Disclosure Of Amyloid Imaging Resultsmentioning

confidence: 99%

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Clinical Use and Utility of Amyloid Imaging

Barthel

Sabri

2017

J Nucl Med

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Currently, 3 amyloid PET tracers are approved and commercially available for clinical use. They allow for the accurate in vivo detection of amyloid plaques, one hallmark of Alzheimer disease. Here, we review the current knowledge on the clinical use and utility of amyloid imaging. Appropriate use criteria for the clinical application of amyloid imaging are established, and most currently available data point to their validity. Visual amyloid image analysis is highly standardized. Disclosure of amyloid imaging results is desired by many cognitively impaired subjects and seems to be safe once appropriate education is delivered to the disclosing clinicians. Regarding clinical utility, increasing evidence points to a change in diagnosis via amyloid imaging in about 30% of cases, to an increase in diagnostic confidence in about 60% of cases, to a change in patient management in about 60% of cases, and specifically to a change in medication in about 40% of cases. Also, amyloid imaging results seem to have a relevant impact on caregivers. Further, initial simulation studies point to a potential positive effect on patient outcome and to cost effectiveness of amyloid imaging. These features, however, will require confirmation in prospective clinical trials. More work is also required to determine the clinical utility of amyloid imaging specifically in subjects with mild cognitive impairment and in comparison with or in conjunction with other Alzheimer disease biomarkers. In summary, the clinical use of amyloid imaging is being studied, and the currently available data point to a relevant clinical utility of this imaging technique. Ongoing research will determine whether this accurate and noninvasive approach to amyloid plaque load detection will translate into a benefit to cognitively impaired subjects. Wi th the successful development and subsequent clinical approval of 18 F-florbetapir, 18 F-florbetaben, and 18 F-flutemetamol, the nuclear imaging community has a set of b-amyloid aggregatetargeting PET tracers in hand for clinical use. They allow the in vivo detection or exclusion of neuritic b-amyloid plaques, one histopathologic hallmark in the neocortex of patients with Alzheimer disease (AD), which previously could be diagnosed only histopathologically after death. Of note, brain b-amyloid accumulation is known to be an early event in this disease (1) and is considered by many as the initial trigger of a cascade of other pathobiochemical and pathophysiologic alterations finally leading to neurodegeneration and related cognitive decline in AD (2).The emergence of amyloid imaging technology is hoped to fill a relevant diagnostic gap in the clinic in cognitively impaired subjects and in AD in particular. Most people would like to get a diagnosis when cognitive symptoms are identified (3). Conversely, dementia diagnosis is often missed and delayed (4,5). With regard to the therapeutic implications of an AD diagnosis, it was reported that older people are willing to accept the relevant side effects of AD-modifying therap...

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Section: Disclosure Of Amyloid Imaging Resultsmentioning

confidence: 99%

“…picture (24), or pointed to the need for adequate education (24,28,29). For cognitively impaired participants of research studies, Lingler et al argued (30) that it is time to disclose the respective amyloid imaging results, again providing adequate pre-and postdisclosure education.…”

Section: Disclosure Of Amyloid Imaging Resultsmentioning

confidence: 99%

Clinical Use and Utility of Amyloid Imaging

Barthel

Sabri

2017

J Nucl Med

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“…The current findings cannot be extrapolated to nongenetic biomarkers because there are potentially important differences [48]. In particular, the presence of nongenetic biomarkers compatible with an “AD profile”, such as a positive amyloid PET scan, is increasingly considered not only as indicative of pathological processes that may eventually lead to the development of AD, but as defining the disease itself, even in the absence of symptoms.…”

Section: Discussionmentioning

confidence: 99%

Psychological, behavioral and social effects of disclosing Alzheimer’s disease biomarkers to research participants: a systematic review

et al. 2016

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BackgroundCurrent Alzheimer’s disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants.MethodsWe performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group.ResultsFourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning.ConclusionIn cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed.Trial registrationPROSPERO international prospective register for systematic reviews CRD42016035388. Registered 19 February 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0212-z) contains supplementary material, which is available to authorized users.

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“…Third, covering the cost of scans could be interpreted as an attempt by the sponsor to unduly influence these potential participants and may violate the ethical principle of justice and erode trust among several stakeholders, including physicians, investigators, patients and families. Finally, covering the cost of clinical scans for cognitively normal participants (e.g., those with a family history or who know they are carriers of the APOE ε4 allele) would violate preliminary recommendations made by expert investigators [26, 27, 55] and sponsored panels [56], which state that until disease-delaying treatments are available and more is understood about the implications of testing results, clinical amyloid imaging should not be performed in people without objective cognitive impairment. If the sponsored registry intends to support preclinical AD trial recruitment, this would necessitate a careful biomarker disclosure process, as discussed above.…”

Section: Sponsorshipmentioning

confidence: 99%

Recruiting to preclinical Alzheimer's disease clinical trials through registries

Grill

2017

A&D Transl Res & Clin Interv

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Participant registries are repositories of individuals who have expressed willingness to learn about studies for which they may be eligible. Registries are increasingly being used to improve recruitment to preclinical Alzheimer's disease (AD) clinical trials, which require large screening efforts to identify adequate numbers of participants who meet enrollment criteria. Recruiting to preclinical AD trials from registries is made more efficient through registry collection of data that permits exclusion of those who will not be eligible and identifies individuals most likely to qualify for trials. Such data could include self-reported disease family history or other risk factors but could also include cognitive, genetic, or biomarker testing outcomes. Few data are available to guide investigators overseeing registries and important ethical questions are likely to arise related to their conduct, especially in registries collecting AD risk information. This article outlines three areas of consideration for registry investigators: informed consent, disclosure, and sponsorship.

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Amyloid imaging, Risk Disclosure and Alzheimer’s Disease: Ethical and Practical Issues

Cited by 58 publications

References 69 publications

Clinical Use and Utility of Amyloid Imaging

Clinical Use and Utility of Amyloid Imaging

Psychological, behavioral and social effects of disclosing Alzheimer’s disease biomarkers to research participants: a systematic review

Recruiting to preclinical Alzheimer's disease clinical trials through registries

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