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Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid
Dubbelman MA, Liu A, Donohue MC, Langford O, Raman R, Rentz DM, Amariglio R, Sperling RA et al.. Neurology, 2025-05-29
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Everyday functioning declines gradually over time in Alzheimer disease (AD), with the earliest changes potentially occurring at the preclinical stage. We investigated how changes in everyday functioning relate to (changes in) amyloid and tau in a large sample of cognitively unimpaired older adults, most of whom had elevated amyloid levels at the start of the study. Methods This prospective study included participants from a 240-week randomized controlled trial of an anti-amyloid drug, solanezumab, and individuals who screen-failed because of a negative amyloid PET scan. A subset (n = 434) underwent repeated tau PET scans. Participants and their study partners completed the Alzheimer's Disease Cooperative Study Activities of Daily Living Prevention Instrument multiple times during the double-blind phase of the trial. Using generalized least-squares models, fit by restricted maximum likelihood, we analyzed how changes in everyday functioning related to amyloid and tau PET. We also correlated changes in amyloid and tau PET with changes in everyday functioning. Results A total of 1,707 participants (71.5 ± 4.7 years, 60% female) showed a marginal decline in everyday functioning. Among individuals with elevated amyloid, those with the highest levels of neocortical and medial temporal tau showed the largest decline in everyday functioning, as reported by the participants and their study partners. Increases in neocortical and medial temporal tau correlated moderately (correlation coefficient ranging from -0.2 to -0.5) with a decline in ADCS ADL-PI scores. Functional changes were not evident with amyloid alone. At the item level, participants and their study partners were most likely to report increased difficulty at the last visit with completing complex activities and selecting and paying for items when shopping. Discussion Higher tau levels are associated with the fastest decline in everyday functioning in the presence of elevated amyloid, and those accumulating more tau show a faster decline in everyday functioning. These findings demonstrate the utility of including sensitive measures of everyday functioning in clinical practice and clinical trials at the stage of preclinical AD. Trial registration information The A4 study, ClinicalTrials.gov ID: NCT02008357; and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration, ClinicalTrials.gov ID: NCT02488720.
Key findings
- Results A total of 1,707 participants (71.5 ± 4.7 years, 60% female) showed a marginal decline in everyday functioning.
- Discussion Higher tau levels are associated with the fastest decline in everyday functioning in the presence of elevated amyloid, and those accumulating more tau show a faster decline in everyday functioning.
- These findings demonstrate the utility of including sensitive measures of everyday functioning in clinical practice and clinical trials at the stage of preclinical AD.
Why it matters
Among 1,707 cognitively unimpaired older adults, those with elevated amyloid and the highest tau levels showed the largest decline in everyday functioning. The authors suggest that sensitive measures of daily functioning could be useful in clinical practice and trials at the preclinical stage.
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Study details
- Study designrandomized controlled trial
- Participants434
- Evidence strengthHigh
How this study scored 68/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 65 of the 96 points we could judge it on, which is 68 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 434 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40440591) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 65 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 65 of the 96 points we could judge it on is 68 out of 100. |
| Total | 68 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000213775
- PubMed: 40440591
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Dubbelman, M. A., Liu, A., Donohue, M. C., Langford, O., Raman, R., Rentz, D. M., et al. (2025). Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. https://doi.org/10.1212/wnl.0000000000213775
Vancouver
Dubbelman MA, Liu A, Donohue MC, Langford O, Raman R, Rentz DM, et al. Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. 2025. doi:10.1212/wnl.0000000000213775. PMID: 40440591.
BibTeX
@article{dubbelman2025-40440591,
author = {Dubbelman, M. A. and Liu, A. and Donohue, M. C. and Langford, O. and Raman, R. and Rentz, D. M. and Amariglio, R. and Sperling, R. A. and others},
title = {{Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid}},
journal = {Neurology},
year = {2025},
doi = {10.1212/wnl.0000000000213775},
pmid = {40440591},
url = {https://doi.org/10.1212/wnl.0000000000213775}
}
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