Evidence map›Paper›PMID 35351181›Full record

Trial reportAlzheimer's research & therapy2022

Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients.

Alexa Pichet Binette, Sebastian Palmqvist, Divya Bali, Gill Farrar, Christopher J Buckley, David A Wolk, Henrik Zetterberg, Kaj Blennow, Shorena Janelidze, Oskar Hansson

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01028053 (A Principal Open-label Study to Assess the Prognostic Usefulness of Flutemetamol), which is not on this map. Cited by 43 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 3 pooled it
6.6field-weighted citation impact, top 2% 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.

NCT01028053 phase3completednot on this map

A Principal Open-label Study to Assess the Prognostic Usefulness of Flutemetamol (18F) Injection for Identifying Subjects With Amnestic Mild Cognitive Impairment Who Will Convert to Clinically Probable Alzheimer's Disease

TypeinterventionalSponsorGE HealthcareRan2009 to 2014Enrolled365ConditionsMild Cognitive Impairment, Alzheimer's DiseaseArmsFlutemetamol (18F) Injection
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
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  5. Trial
  6. Article
  7. Review
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  12. Plasma p-tau217 and p-tau217/AβScientific reports · 2025
    Article
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  17. Review
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  19. Review
  20. Plasma p-tau immunoassays in clinical research for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
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

10 authors at 5 institutions in 3 countries.

Alexa Pichet BinetteClinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden. alexa.pichet_binette@med.lu.se.
Sebastian PalmqvistClinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Divya BaliClinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Gill FarrarGE Healthcare, Chalfont St Giles, UK.
Christopher J BuckleyGE Healthcare, Chalfont St Giles, UK.
David A WolkDepartment of Neurology, Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Shorena Janelidze *Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Oskar Hansson *Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.
Lund University · SESahlgrenska University Hospital · SESkåne University Hospital · SEUniversity of Gothenburg · SEUniversity of Pennsylvania · US

Funding

Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
NIA NIH HHS P30 AG072979
6 · The paper itself

Abstract

backgroundUp to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer's disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI).

methodsWe included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker.

resultsOf all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75-0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82-0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79-0.95, p = 0.07).

conclusionWe identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD.

trial registrationNCT01028053 , registered December 9, 2009.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAmyloid beta-PeptidesDisease ProgressionHumanstau ProteinsAmyloid beta-Peptidestau ProteinsAlzheimer’s diseaseDementiaMild cognitive impairmentPlasma biomarkersp-tau

Identifiers

PMID35351181
PMCPMC8966264
OpenAlexW4220689113

What OpenQuestion holds

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LicenceCC BY
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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.