Evidence map›Paper›PMID 36120786›Full record

ArticleJournal of Alzheimer's disease : JAD2022

High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations.

Andrea Sturchio, Alok K Dwivedi, Tarja Malm, Matthew J A Wood, Roberto Cilia, Jennifer S Sharma, Emily J Hill, Lon S Schneider, Neill R Graff-Radford, Hiroshi Mori and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
5.9field-weighted citation impact, top 3% of its field
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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
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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 at 9 institutions in 7 countries.

Andrea SturchioDepartment of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Alok K DwivediDepartment of Molecular and Translational Medicine, Division of Biostatistics & Epidemiology, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Tarja MalmA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Matthew J A WoodDepartment of Paediatrics, University of Oxford, Oxford, UK.
Roberto CiliaDepartment of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Parkinson and Movement Disorders Unit, Milan, Italy.
Jennifer S SharmaDepartment of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Emily J HillDepartment of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Lon S SchneiderUniversity of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Hiroshi MoriDepartment of Clinical Neuroscience, Medical School, Osaka City University, Sutoku University, Abenoku, Osaka, Nagaoka, Japan.
Georg NüblingGerman Center for Neurodegenerative Diseases, Site Munich, Germany.
Samir El AndaloussiDepartment of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Per SvenningssonDepartment of Clinical Neuroscience, Neuro Svenningsson, Karolinska Institutet, Stockholm, Sweden.
Kariem EzzatDepartment of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Alberto J EspayDepartment of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Dominantly Inherited Alzheimer Consortia (DIAN)
Karolinska Institutet · SEGerman Center for Neurodegenerative Diseases · DETexas Tech University · USUniversity of Cincinnati · USUniversity of Southern California · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversity of Eastern Finland · FIUniversity of Oxford · GBWinnMed · US

Funding

Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8M
NIA NIH HHS P30 AG066530NIA NIH HHS U19 AG032438
6 · The paper itself

Abstract

backgroundIn amyloid-positive individuals at risk for Alzheimer's disease (AD), high soluble 42-amino acid amyloid-β (Aβ42) levels are associated with normal cognition. It is unknown if this relationship applies longitudinally in a genetic cohort.

objectiveTo test the hypothesis that high Aβ42 preserves normal cognition in amyloid-positive individuals with Alzheimer's disease (AD)-causing mutations (APP, PSEN1, or PSEN2) to a greater extent than lower levels of brain amyloid, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), or total tau (t-tau).

methodsCognitive progression was defined as any increase in Clinical Dementia Rating (CDR = 0, normal cognition; 0.5, very mild dementia; 1, mild dementia) over 3 years. Amyloid-positivity was defined as a standard uptake value ratio (SUVR) ≥1.42 by Pittsburgh compound-B positron emission tomography (PiB-PET). We used modified Poisson regression models to estimate relative risk (RR), adjusted for age at onset, sex, education, APOE4 status, and duration of follow-up. The results were confirmed with multiple sensitivity analyses, including Cox regression.

resultsOf 232 mutation carriers, 108 were PiB-PET-positive at baseline, with 43 (39.8%) meeting criteria for progression after 3.3±2.0 years. Soluble Aβ42 levels were higher among CDR non-progressors than CDR progressors. Higher Aβ42 predicted a lower risk of progression (adjusted RR, 0.36; 95% confidence interval [CI], 0.19-0.67; p = 0.002) better than lower SUVR (RR, 0.81; 95% CI, 0.68-0.96; p = 0.018). CSF Aβ42 levels predicting lower risk of progression increased with higher SUVR levels.

conclusionHigh CSF Aβ42 levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations.

Indexed as

Alzheimer DiseaseAmyloidosisCognitive DysfunctionDementiaAmyloid beta-PeptidesBiomarkersCognitionHumansMutationPeptide FragmentsPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkersPeptide Fragmentstau ProteinsAlzheimer’s diseaseamyloid-βatrophycognitionFDG-PET

Identifiers

PMID36120786
PMCPMC9661329
OpenAlexW4296328734

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.