Study: People Don't Freak Out Over Alzheimer's Biomarker Data

— Study looks at short-term effects on depression, anxiety, suicidality

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Is it safe to share Alzheimer's disease biomarker results with older adults who don't have cognitive impairment?

In the short-term at least, the answer appears to be "yes," according to a study of Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) clinical trial candidates.

Older adults who learned they had elevated amyloid levels didn't experience more short-term depression, anxiety, or suicidality than those who learned they didn't have elevated amyloid, reported Joshua Grill, PhD, of University of California Irvine, and colleagues in JAMA Neurology.

Assessments taken 42 to 57 days after amyloid results were disclosed showed similar mean changes in Geriatric Depression Scale scores (0.02 vs 0.04, P=0.90), State-Trait Anxiety Inventory scores (-0.02 vs -0.15, P=0.65), and Columbia Suicide Severity Rating Scale scores (0.0 vs -0.01, P=0.67) between those without and those with elevated amyloid.

"This study is a critical component of the larger global effort to change the way we diagnose and treat Alzheimer's disease," Grill said.

"Someday, we hope that older people will be tested for their risk of developing dementia and started on a therapy to stave off memory problems," Grill told MedPage Today. "Studying the safety and other implications of giving people that information is as important as the studies of the new drugs we hope to use to treat them."

This may be the largest study to date about delivering Alzheimer's biomarker information to cognitively unimpaired older people, and the first to do so across many research sites, Grill added. "It tells us that, at least in the short-term, this can be done safely if a rigorous process for sharing this information is implemented by expert clinicians who receive additional training on how to carefully educate and prepare patients to receive it."

The disclosure process in this study "was very well designed, involving education over several sessions, checking that disclosure was still desired, and extra monitoring of potentially high-risk participants," noted Brian Draper, MBBS, MD, of UNSW in Sydney, who wasn't involved with this study, but who has researched suicide risk in older adults.

"The lack of differences between positive and negative results at the between 1 and 2 months follow-up is promising, but from the perspective of risk of depression, anxiety, and suicide too early, as these outcomes, particularly suicidal behavior, are more likely to start appearing at 3 or more months, particularly after contact with health -- or in this case, research -- services diminishes," Draper told MedPage Today.

"The 3, 6, and 12 month outcomes will be interesting and perhaps more informative about likely risks," he added.

In their study, Grill and colleagues looked at cognitively normal older adults who had been screened for the A4 multisite randomized clinical trial from April 2014 to December 2017. A4 is a phase III trial of the anti-amyloid drug solanezumab in people meeting criteria for preclinical Alzheimer's disease.

Participants underwent an amyloid PET scan and learned their result from an investigator who used a protocol-specified process that began with education about preclinical Alzheimer's and included psychological assessments.

A total of 1,167 people with elevated amyloid levels and 538 participants without elevated amyloid levels were included. Participants had a mean age of about 72; 60.1% were women, and 94.5% were white.

While short-term depression, anxiety, and suicidality scores were similar, the groups differed in two other measures. People with elevated amyloid levels had increased Concern About Alzheimer's Disease scores (raw change in scores for the elevated amyloid group were 0.8, compared with -0.4 for the not-elevated group, P<0.001). And people who did not have elevated amyloid levels experienced a slight increase in Future Time Perspective score (mean score 1.15 points, P<0.001), while there was no change in time perspective among those receiving an elevated amyloid result (mean score 0.33 points).

"These results mark an important milestone," Grill said. "But we need to study the long-term implications -- both positive and negative -- of giving this information to people who may still have 10 or 15 years before they develop memory problems, if they develop them at all."

This is especially important because an earlier study of 50 A4 trial participants showed that approximately 20% of participants with elevated amyloid levels acknowledged considering suicide or physician-assisted death if they were to experience cognitive decline or become a burden to others.

The findings emphasize the importance of the longitudinal evaluation of psychological outcomes being gathered in the trial, the researchers noted. The A4 trial "is the first of its kind and we need much more data in future cohorts of people, including more diverse people and potentially people at younger ages," Grill said.

  • Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

The A4 Study is funded by the National Institute on Aging (NIA), Eli Lilly, the Alzheimer's Association, the GHR Foundation, and other philanthropic supporters.

The researchers disclosed support from, and/or relevant relationships with, the NIA, the National Center for Advancing Translational Sciences, Biogen, Eli Lilly, Genentech, NIH, Cogniciti, Acadia, Avanir, Otsuka, Janssen, Roche, Neurotrack, Merck, Novartis, Takeda, the Alzheimer's Drug Discovery Foundation, Eisai, GHR Foundation, Fidelity, Gates Ventures, Alzheimer's Association, AC Immune, Neurocentria, Cogstate, and Avid Radiopharmaceuticals.

Primary Source

JAMA Neurology

Source Reference: Grill JD, et al "Short-term Psychological Outcomes of Disclosing Amyloid Imaging Results to Research Participants Who Do Not Have Cognitive Impairment" JAMA Neurology 2020; DOI: 10.1001/jamaneurol.2020.2734.