Early Memory Complaints Linked to Alzheimer’s Brain Changes

Summary: A new study finds that reports of cognitive decline from patients and their partners are linked to the accumulation of tau tangles, a hallmark of Alzheimer’s disease. This underscores the importance of addressing memory concerns early.

The study, involving 675 participants, used PET imaging to detect tau and amyloid beta, finding a correlation between these markers and self-reported cognitive decline.

Key Facts:

  • Cognitive decline reports are linked to tau accumulation in the brain.
  • The study highlights the importance of early detection of memory issues.
  • Findings are based on PET imaging of 675 cognitively unimpaired 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 speak with a doctor.

While there are many reasons why someone’s memory may change, researchers from Mass General Brigham who are studying patients prior to diagnosis with Alzheimer’s disease found 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.

This shows an older man.
The team also found that subjective reports from patients and their partners complemented objective tests of cognitive performance. Credit: Neuroscience News

Using imaging, the researchers found reports of cognitive decline were associated with accumulation of tau tangles—a hallmark of Alzheimer’s disease.

Results are published in Neurology, the medical journal of the American Academy of Neurology.

“Something as simple as asking about memory complaints can track with disease severity at the preclinical stage of Alzheimer’s disease,” said senior author Rebecca E. Amariglio, PhD, of the Department of Neurology at Brigham and Women’s Hospital. Amariglio is a clinical neuropsychologist at both Brigham and Women’s Hospital and Massachusetts General Hospital, the founding members of Mass General Brigham.

“We now understand that changes in the brain due to Alzheimer’s disease start well before patients show clinical symptoms detected by a doctor.  There is increasing evidence that individuals themselves or a close family member may notice changes in memory, even before a clinical measure picks up evidence of cognitive impairment.”

The new study, led by first author Michalina F. Jadick, included researchers from across the Brigham and Mass General. The research team designed their study to include participants from the Anti-Amyloid Treatment in Asymptomatic AD/Longitudinal Evaluation of Amyloid Risk (A4/LEARN) and Neurodegeneration studies and the Harvard Aging Brain Study and affiliated studies.

Participants were cognitively unimpaired individuals at risk but not yet diagnosed with Alzheimer’s disease. Each participant and respective study partner completed evaluations of cognitive function for the participant. Each participant also underwent PET imaging to detect levels of tau and amyloid beta.

Across 675 participants, the team found that both 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 that include more diverse participants and follow participants in the longer term are needed.

Amariglio cautions that noticing a change in cognition does not mean that one should leap to the conclusion that a person has Alzheimer’s disease. However, a patient’s or family member’s concerns should not be dismissed if they are worried about cognition.

Authorship: 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 for serving as a site principal investigator for clinical trials funded by Eisai Inc., Eli Lilly and Company, and Genentech which are not related to the content in 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, receives research funding from Eisai and Eli Lilly for public-private partnership clinical trials, receives grant funding from the National Institute on Aging/NIH (P01AG036694), GHR Foundation, and the Alzheimer’s Association. Johnson (spouse) reports consulting fees from Merck and Novartis.

About this memory and Alzheimer’s disease research news

Author: Cassandra Falone
Source: Brigham and Women’s Hospital
Contact: Cassandra Falone – Brigham and Women’s Hospital
Image: The image is credited to Neuroscience News

Original Research: Closed access.
Associations Between Self and Study Partner Report of Cognitive Decline With Regional Tau in a Multicohort Study” by Rebecca E. Amariglio et al. Neurology


Associations Between Self and Study Partner Report of Cognitive Decline With Regional Tau in a Multicohort Study

Background and Objectives

Self-reported cognitive decline is an early behavioral manifestation of Alzheimer disease (AD) at the preclinical stage, often believed 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 among those with preclinical AD.


This cross-sectional study included participants from 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 a cognitively unimpaired (CU) sample of individuals with both nonelevated (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). Global Aβ PET was measured in Centiloids (CLs) with Aβ+ >26 CL. We conducted multiple linear regression analyses to test associations between tau PET and CFI, covarying for amyloid, age, sex, education, and cohort. We also controlled for objective cognitive performance, measured using the Preclinical Alzheimer Cognitive Composite (PACC).


Across 675 CU participants (age = 72.3 ± 6.6 years, female = 59%, Aβ+ = 60%), greater 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 study partner CFI (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 both 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 both self-CFI and study partner CFI. Self-CFI (β = 0.01 [0.001, 0.02], p = 0.03), study partner CFI (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).


Both self-report and study partner report showed associations with tau in addition to Aβ. Additionally, self-report and study partner report were associated with tau above and beyond performance on a neuropsychological composite.

Stratification analyses by Aβ status indicate that associations between self-reported and study partner-reported cognitive concerns with regional tau are driven by those at the preclinical stage of AD, suggesting that both are useful to collect on the early AD continuum.

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