Evidence map›Paper›PMID 41950544›Full record

Trial reportThe journal of prevention of Alzheimer's disease2026

Late-life body mass index and amyloid interaction on cognitive decline in unimpaired older adults.

Wai-Ying Wendy Yau, Rema Raman, Jasmeer Chhatwal, Jeremy J Pruzin, Zahra Shirzadi, Neelum Aggarwal, Adam M Brickman, Petrice M Cogswell, Jonathan Graff-Radford, Jay J Pillai and 6 more

Abstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in The journal of prevention of Alzheimer's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Wai-Ying Wendy YauDepartment of Neurology, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: wyau@mgb.org.
Rema RamanAlzheimer Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA.
Jasmeer ChhatwalDepartment of Neurology, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Jeremy J PruzinDepartment of Neurology, Banner Alzheimer's Institute, Phoenix, AZ, USA.
Zahra ShirzadiDepartment of Neurology, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Neelum AggarwalRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Adam M BrickmanTaub Institute for Research on Alzheimer's Disease and the Aging Brain and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Petrice M CogswellDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Jonathan Graff-RadfordDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Jay J PillaiDepartment of Radiology, Mayo Clinic, Rochester, MN, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Michael S RafiiAlzheimer Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA.
Roy YaariEli Lilly & Co, Indianapolis, ID, USA.
Paul AisenAlzheimer Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA.
Reisa SperlingDepartment of Neurology, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: reisa@bwh.harvard.edu.
A4 and LEARN Study Teams

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe late-life "obesity paradox" of reduced Alzheimer's disease (AD) risk is postulated to be driven by underlying preclinical/prodromal pathology. However, few studies have directly examined the joint associations of BMI and amyloid pathology with cognitive decline, especially in individuals with preclinical AD targeted in prevention trials.

objectiveTo determine whether late-life BMI and amyloid pathology have independent or interactive associations with cognition in clinically unimpaired older adults.

designSecondary analyses of A4 randomized clinical trial and the companion observational LEARN Study (median follow-up 4.7 years).

settingMulticenter across 67 sites in US, Canada, Australia, and Japan.

participantsWe included 1663 participants (Placebo n = 582, Solanezumab n = 563, LEARN n = 518) who were baseline cognitively unimpaired and medically stable, mean age 71.5 ± 4.7 years, 60% women. MEASUREMENTS: BMI and global amyloid burden [Florbetapir PET] were measured at baseline. Cognition was measured longitudinally using Preclinical Alzheimer Cognitive Composite.

resultsHigher BMI and amyloid burden were independently associated with worse baseline cognition. Longitudinally, a BMI*Amyloid*Time interaction emerged: lower/normal BMI was associated with more favorable cognitive trajectory at low amyloid levels, but with faster cognitive decline when amyloid was substantially elevated.

conclusionsOur cross-sectional findings support a negative association between obesity and cognitive aging up to late-life. Longitudinally, we observed an "obesity paradox", where higher/obese BMI was associated with more favorable cognitive trajectories in the presence of advanced amyloid pathology. Together, our findings suggest that future trials targeting obesity to slow late-life cognitive decline may benefit from preferentially enrolling younger individuals or those without substantial amyloid accumulation.

Indexed as

AmyloidAmyloid beta-PeptidesBody Mass IndexCognitive DysfunctionObesityAgedAlzheimer DiseaseFemaleHumansLongitudinal StudiesMaleObesity ParadoxPositron-Emission TomographyAmyloidAmyloid beta-PeptidesAgingAmyloidBMICognitive declineObesity paradoxPreclinical Alzheimer's disease

Identifiers

PMID41950544
PMCPMC13091107

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.