The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design

Daniela Bertens, Betty M. Tijms, Lisa Vermunt, Niels D. Prins, Philip Scheltens, Pieter Jelle Visser, Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. Methods We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers. Results In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers. Discussion Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.

Original languageEnglish
Pages (from-to)513-523
Number of pages11
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume3
Issue number4
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

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title = "The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design",
abstract = "Introduction We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. Methods We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers. Results In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers. Discussion Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.",
keywords = "Alzheimer's disease, Biomarkers, Clinical trial, Cognitive markers, Longitudinal, Preclinical, Prodromal, Sample size estimates",
author = "Daniela Bertens and Tijms, {Betty M.} and Lisa Vermunt and Prins, {Niels D.} and Philip Scheltens and Visser, {Pieter Jelle} and {Alzheimer's Disease Neuroimaging Initiative}",
year = "2017",
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doi = "10.1016/j.trci.2017.08.005",
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journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
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TY - JOUR

T1 - The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease

T2 - Implications for trial design

AU - Bertens, Daniela

AU - Tijms, Betty M.

AU - Vermunt, Lisa

AU - Prins, Niels D.

AU - Scheltens, Philip

AU - Visser, Pieter Jelle

AU - Alzheimer's Disease Neuroimaging Initiative

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Introduction We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. Methods We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers. Results In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers. Discussion Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.

AB - Introduction We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. Methods We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers. Results In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers. Discussion Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.

KW - Alzheimer's disease

KW - Biomarkers

KW - Clinical trial

KW - Cognitive markers

KW - Longitudinal

KW - Preclinical

KW - Prodromal

KW - Sample size estimates

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U2 - 10.1016/j.trci.2017.08.005

DO - 10.1016/j.trci.2017.08.005

M3 - Article

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SP - 513

EP - 523

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

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