Evidence map›Paper›PMID 41085172›Full record

Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Independent effects of white matter lesion volume and APOE ɛ4 on ARIA-H in A4 Study.

Zahra Shirzadi, Aaron P Schultz, Nazila Loghmani, Hyun-Sik Yang, Jeremy Ford, Roy Yaari, Michael Properzi, Wai-Ying W Yau, Lei Liu, Michael S Rafii and 8 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02008357 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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.

NCT02008357 phase3completednot on this map

Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)

TypeinterventionalSponsorEli Lilly and CompanyRan2014 to 2023Enrolled1,169ConditionsCognition DisordersArmsPlacebo, Solanezumab
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Independent effects of white matter lesion volume and APOE ɛ4 on ARIA-H in A4 Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  2. Lecanemab use in Chinese patients with Alzheimer's disease: a 12-month multicenter real-world study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Observational
  3. Article
  4. Response to - Counteracting white matter injury to mitigate APOE4-related ARIA.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Counteracting white matter injury to mitigate APOE 𝜀4-related ARIA.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  6. Article
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

18 authors.

Zahra ShirzadiDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Aaron P SchultzDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nazila LoghmaniDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Hyun-Sik YangDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Jeremy FordDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Roy YaariLilly Corporate Center Indianapolis, Eli Lilly and Company, Indianapolis, Indiana, USA.
Michael ProperziDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Wai-Ying W YauDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Lei LiuDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Michael S RafiiAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
Michael C DonohueAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
Adam M BrickmanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Radiology, Rochester, Minnesota, USA.
Steven M GreenbergDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Paul AisenAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
Reisa A SperlingDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Jasmeer P ChhatwalDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
A4 Study Team

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI Paul S. Aisen · 2016 to 2026
$226.7M
Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PHILIP L DE JAGER · 2020 to 2026
$30.1M
Project 4P41EB015896 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2012 to 2018
$9.8M
A Storage Area Network for Structural and Functional Image AnalysisS10RR023401 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI FISCHL, BRUCE · 2009 to 2009
$2.0M
SILICON GRAPHICS PRISM EXTREME 128P/1TBS10RR023043 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI SORENSEN, ALMA GREGORY · 2006 to 2006
$1.5M
A Siemens MAGNETOTOM Trio 3 Tesla MRI SystemS10RR021110 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2006 to 2006
$500k
BrightFocus Foundation A2023001FCenter for Functional Neuroimaging Technologies P41EB015896Health Enhancement Scientific Program 2U19AG024904-16High-End Instrumentation Grant Program S10RR021110High-End Instrumentation Grant Program S10RR023043High-End Instrumentation Grant Program S10RR023401NCRR NIH HHS S10 RR021110NCRR NIH HHS S10 RR023043NCRR NIH HHS S10 RR023401NIA NIH HHS P30 AG066462NIA NIH HHS U19 AG024904NIBIB NIH HHS P41 EB015896
6 · The paper itself

Abstract

introductionIncreased white matter hyperintensity (WMH) volume is a common but non-specific finding in AD. This study investigates the effect of baseline WMH volume and APOE ε4 on magnetic resonance imaging (MRI)-visible hemorrhagic lesion emergence.

methodsWe included A4 participants with 0/1 hemorrhagic lesion at baseline and >1 post-baseline MRI. We examined age, sex, amyloid, WMH, APOEε4, and cardiovascular risk as predictors of whether people would accrue ≥2 hemorrhagic lesions by their last MRI.

resultsAmong 1097 individuals with 0/1 baseline lesion, 120 had at least two hemorrhagic lesions on their last MRI. Elevated baseline WMH (odds ratio [OR] = 2.3, p = 0.002) and APOE ɛ4/ɛ4 (OR = 4.8, p < 0.001) independently predicted membership to this group. Both hetero- and homozygous APOE ɛ4 carriers with low WMH volume had a low risk of accumulating hemorrhagic lesions. DISCUSSION: These results support the independent consideration of WMH and APOE ɛ4 in the natural history of hemorrhagic lesion accumulation and suggest that individuals with low WMH volume have a low short-term risk, irrespective of APOE genotype.

trial registrationNCT02008357 HIGHLIGHTS: Elevated baseline white matter lesion volume is related to the risk of ARIA-H emergence. The effects of white matter lesion volume and APOE ɛ4 on ARIA-H are independent. APOE ɛ4 carriers with low white matter lesion volume had a low risk of ARIA-H emergence.

Indexed as

Alzheimer DiseaseApolipoprotein E4White MatterAgedBrainFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedApolipoprotein E4amyloid‐related imaging abnormalities–hemorrhagic (ARIA‐H)cerebral amyloid angiopathycerebral microhemorrhageswhite matter hyperintensity

Identifiers

PMID41085172
PMCPMC12519508

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Registered trials

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.