Evidence map›Paper›PMID 34550903›Full record

ArticleNeurology2021

Finding Treatment Effects in Alzheimer Trials in the Face of Disease Progression Heterogeneity.

Roos J Jutten, Sietske A M Sikkes, Wiesje M Van der Flier, Philip Scheltens, Pieter Jelle Visser, Betty M Tijms, Alzheimer's Disease Neuroimaging Initiative

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

Article in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 4 pooled it
18.0field-weighted citation impact, top 1% 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

63 citing papers in PubMed, 4 syntheses or guidelines pooled it, 79 citations in OpenAlex.

  1. Cost-effectiveness of testing biofluid biomarkers to diagnose Alzheimer's disease: a systematic review.The European journal of health economics : HEPAC : health economics in prevention and care · 2026
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  18. Editorial: Real-World Outcomes of Disease-Modifying Therapies Highlight the Need for Diagnostic Biomarkers in Early Alzheimer's Disease.Medical science monitor : international medical journal of experimental and clinical research · 2025
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 3 countries.

Roos J JuttenFrom the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC (R.J.J., S.A.M.S., W.M.V.d.F., P.S., P.J.V., B.M.T.), and Clinical Developmental Psychology & Clinical Neuropsychology (S.A.M.S.), VU University; Alzheimer Center Limburg, School for Mental Health and Neuroscience (P.J.V.), Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics (P.J.V.), Karolinska Institutet, Stockholm, Sweden. rjutten@mgh.harvard.edu.ORCID 0000-0002-3712-4790
Sietske A M SikkesFrom the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC (R.J.J., S.A.M.S., W.M.V.d.F., P.S., P.J.V., B.M.T.), and Clinical Developmental Psychology & Clinical Neuropsychology (S.A.M.S.), VU University; Alzheimer Center Limburg, School for Mental Health and Neuroscience (P.J.V.), Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics (P.J.V.), Karolinska Institutet, Stockholm, Sweden.
Wiesje M Van der FlierFrom the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC (R.J.J., S.A.M.S., W.M.V.d.F., P.S., P.J.V., B.M.T.), and Clinical Developmental Psychology & Clinical Neuropsychology (S.A.M.S.), VU University; Alzheimer Center Limburg, School for Mental Health and Neuroscience (P.J.V.), Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics (P.J.V.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-8766-6224
Philip ScheltensFrom the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC (R.J.J., S.A.M.S., W.M.V.d.F., P.S., P.J.V., B.M.T.), and Clinical Developmental Psychology & Clinical Neuropsychology (S.A.M.S.), VU University; Alzheimer Center Limburg, School for Mental Health and Neuroscience (P.J.V.), Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics (P.J.V.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-1046-6408
Pieter Jelle VisserFrom the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC (R.J.J., S.A.M.S., W.M.V.d.F., P.S., P.J.V., B.M.T.), and Clinical Developmental Psychology & Clinical Neuropsychology (S.A.M.S.), VU University; Alzheimer Center Limburg, School for Mental Health and Neuroscience (P.J.V.), Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics (P.J.V.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-8008-9727
Betty M TijmsFrom the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC (R.J.J., S.A.M.S., W.M.V.d.F., P.S., P.J.V., B.M.T.), and Clinical Developmental Psychology & Clinical Neuropsychology (S.A.M.S.), VU University; Alzheimer Center Limburg, School for Mental Health and Neuroscience (P.J.V.), Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics (P.J.V.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-2612-1797
Alzheimer's Disease Neuroimaging Initiative
Karolinska Institutet · SEAmsterdam Neuroscience · NL

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

objectiveTo investigate the influence of heterogeneity in disease progression for detecting treatment effects in Alzheimer disease (AD) trials, using a simulation study.

methodsIndividuals with an abnormal amyloid PET scan, diagnosis of mild cognitive impairment or dementia, baseline Mini-Mental State Examination (MMSE) score ≥24, global Clinical Dementia Rating (CDR) score of 0.5, and ≥1 follow-up cognitive assessment were selected from the Alzheimer's Disease Neuroimaging Initiative database (n = 302, age 73 ± 6.7; 44% female; 16.1 ± 2.7 years of education; 69%

resultsIndividual trajectories on all cognitive outcomes were highly variable, and the 95% ranges of possible effect sizes at 18 months were broad (e.g., ranging from 0.35 improvement to 0.35 decline on the CDR-SB). Results of recent anti-amyloid trials mostly fell within these 95% ranges of effect sizes.

conclusionsIndividuals with early AD show heterogeneity in disease progression, which increases when stratifying on risk factors associated with progression. We provide guidance for a priori effect sizes on cognitive outcomes for detecting true change, which is crucial for future AD trials.

Indexed as

Disease ProgressionModels, StatisticalTreatment OutcomeAgedAged, 80 and overAlzheimer DiseaseFemaleHumansMaleMiddle AgedNeuroprotective AgentsRisk FactorsNeuroprotective Agents

Identifiers

PMID34550903
PMCPMC8205463
OpenAlexW3172344409

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.