Short-term Psychological Outcomes of Disclosing Amyloid Imaging Results to Research Participants Who Do Not Have Cognitive Impairment - PubMed (original) (raw)

Clinical Trial

Short-term Psychological Outcomes of Disclosing Amyloid Imaging Results to Research Participants Who Do Not Have Cognitive Impairment

Joshua D Grill et al. JAMA Neurol. 2020.

Abstract

Importance: The goal of preclinical Alzheimer disease (AD) clinical trials is to move diagnosis and treatment to presymptomatic stages, which will require biomarker testing and disclosure.

Objective: To assess the short-term psychological outcomes of disclosing amyloid positron emission tomography results to older adults who did not have cognitive impairment.

Design, setting, and participants: This observational study included participants who were screening for a multisite randomized clinical trial that began on February 28, 2014, and is anticipated to be completed in 2022. Participants aged 65 to 85 years who had no known cognitive impairments underwent an amyloid positron emission tomography scan and learned their result from an investigator who used a protocol-specified process that included prescan education and psychological assessments. This report compares participants with elevated amyloid levels with at least 1 available outcome measure with participants who did not have elevated amyloid levels who enrolled in an observational cohort study and received further evaluations. Data were collected from April 2014 to December 2017 and analyzed from March 2019 to October 2019.

Exposures: A personal biomarker result described as either an elevated or not elevated amyloid level.

Main outcomes and measures: To assess the immediate and short-term psychological outcome of disclosure, the following validated measures were used: the Geriatric Depression Scale, the state items from the State-Trait Anxiety Inventory, and the Columbia Suicide Severity Rating Scale, as well as the Concerns About AD Scale and the Future Time Perspective Scale to assess changes in participants' perceived risk for AD and perceived remaining life span, respectively.

Results: A total of 1167 participants with elevated amyloid levels and 538 participants with not elevated amyloid levels were included. Participants had a mean (SD) age of 71.5 (4.7) years, 1025 (60.1%) were women, and most were white (1611 [94.5%]) and non-Latino (1638 [96.1%]). Compared with participants who learned that they had a not elevated amyloid result, individuals who learned of an elevated amyloid result were no more likely to experience short-term increases in depression (mean [SD] change in the Geriatric Depression Scale score, 0.02 [1.3] vs 0.04 [1.3]; P = .90), anxiety (mean [SD] change in State-Trait Anxiety Inventory score, -0.02 [3.2] vs -0.15 [3.0]; P = .65), or suicidality (mean [SD] change in the Columbia Suicide Severity Rating Scale score, 0.0 [0.4] vs -0.01 [0.5]; P = .67). Participants with elevated amyloid levels had increased Concern About AD scores (raw change in scores: elevated amyloid group, 0.8 [3.9]; not elevated amyloid group, -0.4 [3.8]; P < .001). Participants with not elevated amyloid levels experienced a slight increase in Future Time Perspective score(mean [SD] score, 1.15 [7.4] points; P < .001); there was no change in time perspective among those receiving an elevated amyloid result (mean [SD] score, 0.33 [7.8] points).

Conclusions and relevance: In this observational preclinical AD study, participants who learned they had elevated amyloid levels did not experience short-term negative psychological sequelae compared with persons who learned they did not have elevated amyloid levels.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Grill reports research support from Biogen, Eli Lilly, Genentech, and the National Institutes of Health and consulting for Cogniciti. Dr Sultzer reports consulting for Acadia, Avanir, and Otsuka; employment by University of California and Department of Veterans Affairs; and grants from the National Institutes of Health. Dr Raman and Ms Ernstrom reports research support from the National Institute on Aging, Eli Lilly, and Janssen. Dr Donohue’s spouse is a fulltime employee of Janssen; he has also served on scientific advisory boards for Biogen and Eli Lilly, consulted for Roche, received grants from the National Institute on Aging and Eli Lilly during the conduct of the study, received grants from Janssen outside the submitted work, and received personal fees from Biogen, Neurotrack, Roche, and Eli Lilly outside the submitted work. Dr Johnson reports grants from the National Institutes of Health; personal fees from Biogen, Merck, Novartis, Takeda, Roche/Genentech, and Janssen; and grants from Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation during the conduct of the study. Dr Aisen reports grants from the National Institute on Aging, Foundation for the National Institutes of Health, the Alzheimer's Association, Janssen, Eli Lilly, and Eisai and personal fees from Merck, Roche, Biogen, ImmunoBrain Checkpoint, and Samus outside the submitted work. Dr Sperling’s institution has received research support from Eli Lilly, but she does not receive any personal income; she has also received research grants from the National Institute on Aging, Eli Lilly, GHR Foundation, Fidelity, Gates Ventures, and the Alzheimer’s Association; served as a consultant for AC Immune, Biogen, Eisai, Neurocentria, Roche, Novartis, and Takeda; received nonfinancial support from Cogstate and Mount Sinai during the conduct of the study; and received grants and personal fees from Janssen outside the submitted work. Dr Karlawish is a site investigator for clinical trials supported by Lilly Inc, including the A4 Study, and Novartis. Dr Burns reported grants from the National Institutes of Health and Eli Lilly during the conduct of the study and grants from Avid Radiopharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Screening Visit Schedule for the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study

Screening required 4 to 5 visits, depending on whether participants completed the optional lumbar puncture. Education, informed consent, and psychological assessment were completed at visit 1. Amyloid results were disclosed at visit 3. Immediately after disclosure, associated assessments were performed (the Concerns About AD and the Future Time Perspective [FTP] scales); the Impact of Events Scale (IES) was collected by telephone within 72 hours of disclosure for all participants. Participants with elevated and not elevated amyloid levels selected for the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration trial underwent a baseline assessment at visit 6, when postdisclosure psychological assessments were collected. CSSRS indicates Columbia Suicide Severity Rating Scale; GDS, Geriatric Depression Scale; LP, lumbar puncture; MRI, magnetic resonance imaging; PET, positron emission tomography; STAI, State-Trait Anxiety Scale; V, visit.

Figure 2.. Changes in Psychological Outcomes After Amyloid Disclosure

Box plots of the group (elevated amyloid levels vs not elevated amyloid levels) changes are plotted for the Geriatric Depression Scale (GDS) (A), State-Trait Anxiety Scale (STAI) (B), and Columbia Suicide Severity Rating Scale (CSSRS) (C). D, The group data from the Impact of Events Scale (IES), collected by telephone 24 to 72 hours after amyloid level disclosure.

Figure 3.. Change in Concerns About Alzheimer Disease (AD) Responses

The changes in the proportion of participants endorsing the 2 most extreme levels of agreement (somewhat and strongly agree) on the Concerns About AD Scale are plotted for the elevated amyloid group (n = 1167) and the not elevated amyloid group (n = 538). Bars above the x-axis represent an increase in the proportion of individuals acknowledging the highest level of concern about AD; bars below the x-axis represent a decrease in the proportion of individuals acknowledging the highest level of concern.

References

1. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270-279. doi: 10.1016/j.jalz.2011.03.008 -DOI -PMC -PubMed
1. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263-269. doi: 10.1016/j.jalz.2011.03.005 -DOI -PMC -PubMed
1. McKhann GM. Changing concepts of Alzheimer disease. JAMA. 2011;305(23):2458-2459. doi: 10.1001/jama.2011.810 -DOI -PubMed
1. Cummings JL, Cole G. Alzheimer disease. JAMA. 2002;287(18):2335-2338. doi: 10.1001/jama.287.18.2335 -DOI -PubMed
1. Morris JC, Roe CM, Grant EA, et al. Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Arch Neurol. 2009;66(12):1469-1475. doi: 10.1001/archneurol.2009.269 -DOI -PMC -PubMed

Short-term Psychological Outcomes of Disclosing Amyloid Imaging Results to Research Participants Who Do Not Have Cognitive Impairment - PubMed (original) (raw)