Performance of Simulated Real-Life Daily Functioning Test Associated With Risk of Alzheimer Disease

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Findings from a recent exploratory study suggest that assessing daily functioning in a more sensitive way may identify Alzheimer disease before a patient develops more pronounced cognitive changes.

Gad Marshall, MD, director of clinical trials at the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital

Gad Marshall, MD

Recently published in the Journal of Alzheimer’s Disease, a new study showed that an older adult’s performance on a brief phone menu test was associated with Alzheimer disease (AD) pathologies, including amyloid and tau depositions in the brain. These preliminary findings suggest the test can detect the earliest changes in daily functioning in patients at risk of AD and could help inform prevention trials testing treatments for AD before the start of cognitive decline symptoms.1,2

Among 77 participants who were clinically normal, approximately under 26% of these patients showed evidence of elevated amyloid and tau in the brain regions while experiencing difficulties with challenging tasks of the daily functioning assessment. Authors noted these findings as significant since most people with AD begin with short-term memory difficulties, word-finding difficulties, and issues with sense of direction as well as have decreased motivation, depression, irritability, and anxiety.

“This test is a more objective assessment of an aspect of daily functioning as opposed to our typical way of using a questionnaire filled out by somebody who knows the individual well. The implication is we may in fact detect a clinically meaningful change much earlier than we anticipate,” senior author Gad Marshall, MD, director of clinical trials at the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, said in a statement.1

The study examined the cross-sectional relationship between a performance-based activities of daily living test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in 77 cognitively normal older adult patients. The APT included 3 tasks an older patient may encounter on a phone menu such as a prescription refill (APT-Script), health insurance company call (APT-PCP) and a banking transaction (APT-Bank). The test asked participants to navigate an interactive voice response system for these specific tasks. In addition, the patients and their study partner completed other assessments on a variety of daily activities, which were then followed by standard cognitive testing and brain scans.

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Despite no significant associations between the APT tasks and tau or amyloid alone, there was an association observed between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau (standardized β = −0.61, t(69) = −2.31, P = .02; model R2 = .17, F(6, 69) = 2.30, P = .04). There was also an association observed with the APT-PCP task and interactions between amyloid and inferior temporal (β = −0.62, t(69) = −2.65, P = .01; model R2 = .22, F(6, 69) = 3.23, P = .007) and precuneus tau (β = −0.51, t(69) = −2.01, P = .048; model R2 = .19, F(6, 69) = 2.63, P = .02).

Although most participants were able to complete the tasks on their own outside of a clinical setting in a timely manner, the assessment only represents a small part of daily functioning that not everyone utilizes. Authors also noted that the lack of diversity among the participants as 86% of the cohort were White and only 9% were nonHispanic. Therefore, investigators recommended further research on these findings to determine if they can be replicated in more diverse patient populations and if associations emerge with difficulty completing the simpler tasks over a longer period.

"Although these findings are preliminary, they signal that there is an association between an objective measurement of instrumental activities of daily living (i.e., the Harvard APT task) and the interaction of tau and amyloid in a sample of cognitively normal older adults,” lead author Chris Gonzalez, MS, 4th-year PhD student in clinical neuropsychology at Rosalind Franklin University of Medicine and Science, said in a statement.1 “Having a task like the Harvard APT could better capture an individual's overall ability to complete complex everyday tasks rather than the questionnaires that are given to patients and their informants to better understand the preclinical stages of Alzheimer disease.”

REFERENCES
1. Phone Menu Test Detects Who May Be at Risk of Alzheimer’s Disease. News Release. Mass General Brigham. Published June 20, 2023. Accessed September 11, 2023. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/phone-menu-test-detects-risk-of-alzheimers
2. Gonzalez C, Mimmack KJ, Amariglio RE, et al. Associations of the Harvard Automated Phone Task and Alzheimer's Disease Pathology in Cognitively Normal Older Adults: Preliminary Findings. J Alzheimers Dis. 2023;94(1):217-226. doi:10.3233/JAD-220885
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