Evidence map›Paper›PMID 25681452›Full record

SynthesisNeurology2015

Differences in Alzheimer disease clinical trial outcomes based on age of the participants.

Lon S Schneider, Richard E Kennedy, Guoqiao Wang, Gary R Cutter

Abstract readComparative StudyMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 4 pooled it
–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

23 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Article
  10. Comparison of two preprocessing methods forEuropean journal of nuclear medicine and molecular imaging · 2025
    Article
  11. Article
  12. The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  13. Prognostic value of imaging-based ATN profiles in a memory clinic cohort.European journal of nuclear medicine and molecular imaging · 2023
    Article
  14. Review
  15. Heterogeneity in Alzheimer's Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Observational
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Lon S SchneiderFrom the Departments of Psychiatry and Neurology (L.S.S.), Keck School of Medicine of USC, Los Angeles, CA; Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine (R.E.K.), and Department of Biostatistics (G.W., G.R.C.), University of Alabama at Birmingham. lschneid@usc.edu.
Richard E KennedyFrom the Departments of Psychiatry and Neurology (L.S.S.), Keck School of Medicine of USC, Los Angeles, CA; Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine (R.E.K.), and Department of Biostatistics (G.W., G.R.C.), University of Alabama at Birmingham.
Guoqiao WangFrom the Departments of Psychiatry and Neurology (L.S.S.), Keck School of Medicine of USC, Los Angeles, CA; Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine (R.E.K.), and Department of Biostatistics (G.W., G.R.C.), University of Alabama at Birmingham.
Gary R CutterFrom the Departments of Psychiatry and Neurology (L.S.S.), Keck School of Medicine of USC, Los Angeles, CA; Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine (R.E.K.), and Department of Biostatistics (G.W., G.R.C.), University of Alabama at Birmingham.

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRASKIE, MEREDITH NICOLE · 1985 to 2019
$41.0M
Synthesis of Longer-Term Alzheimer Disease Studies in Order to Model and ImproveR01AG037561 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SCHNEIDER, LON S · 2011 to 2013
$1.6M
NIA NIH HHS P50 AG005142NIA NIH HHS R01 AG037561
6 · The paper itself

Abstract

objectiveWe tested the a priori hypothesis that older participants differ in rates of decline on cognitive outcomes compared with younger participants, and examined the potential effect of age distributions on individual clinical trial outcomes.

methodsFrom a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, we included a cohort of 2,793 participants for whom there were baseline demographic data and at least one postbaseline cognitive assessment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinical Dementia Rating-Sum of Boxes (CDR-SB), or Mini-Mental State Examination (MMSE). We used mixed-effects models (random coefficient models) to estimate change on the outcomes across 7 age groups ranging from younger than 61 years to older than 85 years after adjusting for education.

resultsSignificant worsening occurred in all age groups on all outcomes over time. The 4 older groups, aged 71 years and older, showed slower rates of decline on the ADAS-cog than the younger groups (p = 0.001). The older groups scored 2-3, 2-5, and 4-6 points better than the younger groups at 12, 18, and 24 months, respectively. There were similar differences across age groups for the MMSE, but not for the CDR-SB.

conclusionsThe differences in change on the ADAS-cog between older and younger participants are substantially greater than differences expected between experimental drugs and placebo in current trials or differences between marketed cholinesterase inhibitors and placebo. The clinical interpretation of change on the ADAS-cog or MMSE differs depending on age. Until predictors of decline are better understood, considering effects of age on rates of change is particularly important regarding clinical practice and outcomes of trials.

Indexed as

AgedAged, 80 and overAgingAlzheimer DiseaseCholinesterase InhibitorsClinical Trials as TopicCohort StudiesDouble-Blind MethodFemaleHumansMaleMiddle AgedNeuropsychological TestsTreatment OutcomeCholinesterase Inhibitors

Identifiers

PMID25681452
PMCPMC4371405

What OpenQuestion holds

Textmetadata
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.