Return of Amyloid Imaging Results (RAISR Study) — RAISR  

Mild Cognitive Impairment Clinical Trial

Official title: Return of Amyloid Imaging Results

Status Completed

Clinical Trial Summary

Diagnostic tests designed to detect Alzheimer's disease (AD) pathology are increasingly popular in research on cognitive aging and AD. Due to concerns that information from such tests may be misunderstood, psychologically harmful, and of unclear clinical significance, results of pre mortem tests of AD pathology have typically been withheld from research participants. However, as the reliability and potential clinical significance of tests like brain amyloid imaging have become clear, there is a pressing need to revisit the practice of unilaterally withholding such information from research participants and identify responsible approaches to communicating individual results. Amyloid imaging results may be particularly relevant to mild cognitive impairment (MCI), a population for whom a growing body of evidence suggests that such testing may provide valuable prognostic and planning information, despite the unavailability of interventions to alter one's clinical course. Our preliminary work suggests that research participants with MCI and their family members are receptive to and capable of understanding information about the purpose, results, and implications of amyloid imaging when presented using a standardized approach developed by our interdisciplinary team. Building on this work, the proposed study will examine a well characterized sample of MCI care dyads (patient + family member) who will be randomized to either receive the opportunity to decide if they would like to pursue an amyloid PET Scan, or be randomized to not receive that opportunity (and will serve in the no-scan comparison group). This study aims to test hypotheses that examine how receiving amyloid imaging results will impact understanding of, and perceived self-efficacy for coping with, MCI among both patients and care partners.

Clinical Trial Description

Objective:

Advances in amyloid imaging are leading to unprecedented changes in research on cognitive aging. We intend to characterize the way individuals respond to learning of the results of their amyloid imaging scans, understand the context in which decisions to obtain results of brain amyloid status are made, and examine the impact of such knowledge over the first year following results disclosure.

Specific Aim:

To determine the effect of receiving amyloid imaging results on understanding of, and perceived efficacy to cope with, Mild Cognitive Impairment (MCI) as a potential precursor to dementia.

Hypothesis 1. MCI care dyads who receive amyloid imaging results, using the text and visual aids developed by our interdisciplinary team, will a) perform better on objective assessments of basic knowledge about MCI and its relation to AD, and b) report lower levels of perceived ambiguity about what MCI means, as compared to control MCI care dyads not receiving amyloid imaging.

Hypothesis 2. MCI care dyads who receive the patient's amyloid imaging results, using the text and visual aids developed by our interdisciplinary team, will report higher levels of perceived efficacy to cope with MCI as compared to those not participating in amyloid imaging.

Background: Amyloid imaging is a brain scanning technique that uses radioligands along with positron emission tomography (PET) to detect the presence of neuritic plaques associated with Alzheimer's disease (AD). Evidence accumulating over the past decade suggests that current imaging techniques show fibrillar amyloid beta deposits in patients with known AD in a pattern consistent with post mortem pathological descriptions of amyloid plaque distribution (1,2). Although the prognostic utility of amyloid imaging in cognitively healthy older adults remains unclear, it is increasingly evident that brain amyloid positivity may have significant implications for the long-term outcomes of individuals with mild cognitive impairment (MCI).

Across 5 published studies, 155 persons with both amnestic and other subtypes of MCI have received amyloid PET scans and been followed longitudinally (3-7). Of these 155 individuals, 101 were amyloid positive at baseline, just over half (n = 53) of whom converted to dementia within 1 to 3 years. By contrast, only 7.4% (n = 4) of those who were amyloid negative at baseline converted to dementia within the same time period.

This body of research suggests that, regardless of MCI subtype, amyloid imaging is a unique and powerful indicator of clinical outcomes in MCI. This mounting evidence of the prognostic value of amyloid imaging underscores the significance of providing amyloid research participants who have MCI with information about, and the choice of, receiving their amyloid PET scan results. It is recognized that such results are not medically actionable because there are no FDA-approved treatments for MCI or otherwise effective means of slowing progression to dementia.

Despite the fact that amyloid PET research results are not medically actionable in MCI, preliminary findings from our team's investigation of disclosing mock amyloid scan results to MCI care dyads (patient + family member) indicate that these individuals are highly receptive to and generally capable of understanding information about amyloid-based biomarkers for AD, including the limitations and limited clinical utility of such testing.

Significance: Amyloid imaging advances are leading to unprecedented changes in research on cognitive aging and AD. As the field transitions into an era of pre-mortem testing for AD pathology, amyloid imaging is playing a key role in identifying candidates for and evaluating effectiveness in anti-amyloid clinical trials. Whereas tests of cognitive function have long been the gold standard for measuring treatment response, amyloid-based markers are rapidly being adopted as secondary outcome measures and, in some cases, methodologies of choice for evaluating the effectiveness of experimental therapies targeting AD. In clinical practice, the recent FDA approval of the commercial amyloid imaging agent, florbetapir, suggests that in the near future tests of pre-mortem AD pathology, while not sufficient to render a dementia diagnosis, may augment clinical evaluations of cognitive impairment. Findings from this research will lead to guidelines to assist clinicians in counseling and supporting individuals who are considering undergoing such testing. ;

Related Conditions & MeSH terms

• Amyloidosis
• Cognitive Dysfunction
• Mild Cognitive Impairment

• NCT number: NCT03121118
• Study type: Observational
• Source: University of Pittsburgh
• Status: Completed
• Start date: September 17, 2014
• Completion date: May 31, 2020