Summary: A new study finds that reports of cognitive decline in patients and their partners are linked to the accumulation of tau tangles, a hallmark of Alzheimer’s disease. This highlights the importance of treating memory problems quickly.
The study, involving 675 participants, used PET imaging to detect tau and beta-amyloid, finding a correlation between these markers and self-reported cognitive decline.
Highlights:
- Reports of cognitive decline are linked to the accumulation of tau in the brain.
- The study highlights the importance of early detection of memory problems.
- Results are based on PET imaging of 675 cognitively healthy individuals.
Source: Brigham and Women’s Hospital
A new study adds further evidence that when a patient or family member notices signs of persistent memory loss, it’s important to talk to a doctor.
Although there are many reasons why a person’s memory may change, researchers at Mass General Brigham who study patients before Alzheimer’s disease are diagnosed have discovered changes in the brain when patients and their Study partners (those who could answer questions about their daily cognitive function) reported a decline in cognition.
Using imaging, researchers found that reports of cognitive decline were associated with an accumulation of Tau tangles, a hallmark of Alzheimer’s disease.
The results are published in Neurology, the medical journal of the American Academy of Neurology.
“Something as simple as asking about memory problems can track disease severity in the preclinical stage of Alzheimer’s disease,” said lead author Rebecca E. Amariglio, PhD, of the Department of Neurology from Brigham and Women’s Hospital. Amariglio is a clinical neuropsychologist at Brigham and Women’s Hospital and Massachusetts General Hospital, the founding members of Mass General Brigham.
“We now understand that brain changes caused by Alzheimer’s disease begin long before patients show clinical symptoms detected by a doctor. There is growing evidence that individuals themselves or a close family member may notice changes in memory, even before a clinical measure detects signs of cognitive impairment.
The new study, led by first author Michalina F. Jadick, included researchers from Brigham and Mass General. The research team designed their study to include participants from the Anti-Amyloid Treatment in Asymptomatic AD/Longitudinal Assessment of Amyloid Risk (A4/LEARN) and Neurodegeneration studies, as well as the Harvard Aging Brain Study and affiliated studies.
The participants were people at risk, cognitively impaired, but who had not yet been diagnosed with Alzheimer’s disease. Each participant and respective study partner completed assessments of the participant’s cognitive function. Each participant also underwent PET imaging to detect levels of tau and beta-amyloid.
In 675 participants, the team found that amyloid and tau were associated with greater self-reported decline in cognitive function. The team also found that subjective reports from patients and their partners complemented objective tests of cognitive performance.
The authors note that the study was limited by the fact that most participants were white and highly educated. Future studies including more diverse participants and following participants longer term are needed.
Amariglio cautions that noticing a change in cognition does not mean jumping to the conclusion that a person has Alzheimer’s disease. However, a patient or family member’s concerns should not be ignored if they are worried about their cognitive functions.
Paternity: In addition to Jadick and Amariglio, Mass General Brigham authors include Hannah Klinger (MGH), Rachel F. Buckley (MGH, BWH), Gad A. Marshall (MGH, BWH), Patrizia Vannini (MGH, BWH), Dorene M. Rentz . (MGH, BWH), Keith A. Johnson (MGH, BWH), Reisa A. Sperling (MGH, BWH), Talia Robinson (BWH), and Michelle E. Farrell (BWH).
Disclosures: Marshall has received research salary support as the site’s principal investigator for clinical trials funded by Eisai Inc., Eli Lilly and Company, and Genentech that are unrelated to the content of the manuscript. Johnson is a consultant for Merck and Novartis.
Sperling has served as a paid consultant for AbbVie, ACImmune, Acumen, Alector, Bristol Myers Squibb, Genentech, Ionis, Janssen, Nervgen, Oligomerix, Prothena, Roche, and Vaxxinity, and receives research funding from Eisai and Eli Lilly for a public partnership -private. clinical trials, receives a grant from the National Institute on Aging/NIH (P01AG036694), the GHR Foundation, and the Alzheimer’s Association. Johnson (spouse) reports consulting fees from Merck and Novartis.
About this memory and current research on Alzheimer’s disease
Author: Cassandra Falone
Source: Brigham and Women’s Hospital
Contact: Cassandra Falone – Brigham and Women’s Hospital
Picture: Image is credited to Neuroscience News
Original research: Closed access.
“Reporting Associations Between Self and Study Partners on Cognitive Decline with Regional Tau in a Multicohort Study” by Rebecca E. Amariglio et al. Neurology
Abstract
Associations Between Self and Study Partner Reporting Cognitive Decline With Regional Tau in a Multicohort Study
Context and objectives
Self-reported cognitive decline is an early behavioral manifestation of Alzheimer’s disease (AD) in the preclinical stage, often considered to precede concerns reported by a study partner. Previous work shows cross-sectional associations with β-amyloid (Aβ) status and self-reported and study partner-reported cognitive decline, but less is known about their associations with tau deposition, particularly in people with preclinical AD.
Methods
This cross-sectional study included participants in the Anti-Amyloid Treatment in Asymptomatic AD/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies (N=444) and the Harvard Aging Brain Study and affiliated studies (N=231), which resulted in to a cognitive study. unaltered (UC) sample of individuals with both non-elevated Aβ (Aβ−) and elevated Aβ (Aβ+). All participants and study partners completed the Cognitive Function Index (CFI).
Two regional tau composites were derived by averaging flortaucipir PET uptake in the medial temporal lobe (MTL) and neocortex (NEO). Overall PET Aβ was measured in centiloids (CL) with Aβ+ > 26 CL. We performed several linear regression analyzes to test associations between Tau PET and CFI, depending on amyloid, age, sex, education, and cohort. We also monitored objective cognitive performance, measured using the Preclinical Alzheimer Cognitive Composite (PACC).
Results
Among 675 UC participants (age = 72.3 ± 6.6 years, female = 59%, Aβ+ = 60%), higher tau was associated with greater self-CFI (MTL: β = 0.28 (0.12, 0.44), p < 0.001, and NEO: β = 0.26 (0.09, 0.42), p = 0.002) and partner of the CFI study (MTL: β = 0.28 (0.14, 0.41), p < 0.001, and NEO: β = 0.31 (0.17, 0.44), p < 0.001). Significant associations between CFI measures and MTL/NEO tau PET were driven by Aβ+. Continuous Aβ showed an independent effect on CFI in addition to MTL and NEO tau for self-CFI and study partner CFI. Auto-CFI (β = 0.01 (0.001, 0.02), p = 0.03), partner of the CFI study (β = 0.01 (0.003, 0.02), p = 0.01), and the PACC (β = −0.02 (−0.03, −0.01), p < 0.001) were independently associated with MTL tau, but for NEO tau, PACC (β = −0.02 (−0.03, −0.01), p < 0.001) and study partner report (β = 0.01 (0.004, 0.02), p = 0.002) were associated, but not self-CFI (β = 0.01 (−0.001, 0.02), p = 0.10).
Discussion
Self-report and study partner report showed associations with tau in addition to Aβ. Additionally, self-report and study partner report were associated with higher tau performance than a neuropsychological composite.
Stratification analyzes by Aβ status indicate that associations between self-reported and study partner-reported cognitive concerns regarding regional tau are driven by those in the preclinical stage of AD, suggesting that it is useful to collect both on the early AD continuum.