Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project

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Abstract

Importance: Biomarkers do not determine conversion to Alzheimer disease (AD) perfectly, and criteria do not specify how to take patient characteristics into account. Consequently, biomarker use may be challenging for clinicians, especially in patients with mild cognitive impairment (MCI).

Objective: To construct biomarker-based prognostic models that enable determination of future AD dementia in patients with MCI.

Design, Setting, and Participants: This study is part of the Alzheimer's Biomarkers in Daily Practice (ABIDE) project. A total of 525 patients with MCI from the Amsterdam Dementia Cohort (longitudinal cohort, tertiary referral center) were studied. All patients had their baseline visit to a memory clinic from September 1, 1997, through August 31, 2014. Prognostic models were constructed by Cox proportional hazards regression with patient characteristics (age, sex, and Mini-Mental State Examination [MMSE] score), magnetic resonance imaging (MRI) biomarkers (hippocampal volume, normalized whole-brain volume), cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, tau), and combined biomarkers. Data were analyzed from November 1, 2015, to October 1, 2016.

Main Outcomes and Measures: Clinical end points were AD dementia and any type of dementia after 1 and 3 years.

Results: Of the 525 patients, 210 (40.0%) were female, and the mean (SD) age was 67.3 (8.4) years. On the basis of age, sex, and MMSE score only, the 3-year progression risk to AD dementia ranged from 26% (95% CI, 19%-34%) in younger men with MMSE scores of 29 to 76% (95% CI, 65%-84%) in older women with MMSE scores of 24 (1-year risk: 6% [95% CI, 4%-9%] to 24% [95% CI, 18%-32%]). Three- and 1-year progression risks were 86% (95% CI, 71%-95%) and 27% (95% CI, 17%-41%) when MRI results were abnormal, 82% (95% CI, 73%-89%) and 26% (95% CI, 20%-33%) when CSF test results were abnormal, and 89% (95% CI, 79%-95%) and 26% (95% CI, 18%-36%) when the results of both tests were abnormal. Conversely, 3- and 1-year progression risks were 18% (95% CI, 13%-27%) and 3% (95% CI, 2%-5%) after normal MRI results, 6% (95% CI, 3%-9%) and 1% (95% CI, 0.5%-2%) after normal CSF test results, and 4% (95% CI, 2%-7%) and 0.5% (95% CI, 0.2%-1%) after combined normal MRI and CSF test results. The prognostic value of models determining any type of dementia were in the same order of magnitude although somewhat lower. External validation in Alzheimer's Disease Neuroimaging Initiative 2 showed that our models were highly robust.

Conclusions and Relevance: This study provides biomarker-based prognostic models that may help determine AD dementia and any type of dementia in patients with MCI at the individual level. This finding supports clinical decision making and application of biomarkers in daily practice.

Original languageEnglish
Pages (from-to)1481-1491
Number of pages11
JournalJAMA Neurology
Volume74
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017

Cite this

@article{7433541274b044eca8fd219dded10a72,
title = "Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project",
abstract = "Importance: Biomarkers do not determine conversion to Alzheimer disease (AD) perfectly, and criteria do not specify how to take patient characteristics into account. Consequently, biomarker use may be challenging for clinicians, especially in patients with mild cognitive impairment (MCI).Objective: To construct biomarker-based prognostic models that enable determination of future AD dementia in patients with MCI.Design, Setting, and Participants: This study is part of the Alzheimer's Biomarkers in Daily Practice (ABIDE) project. A total of 525 patients with MCI from the Amsterdam Dementia Cohort (longitudinal cohort, tertiary referral center) were studied. All patients had their baseline visit to a memory clinic from September 1, 1997, through August 31, 2014. Prognostic models were constructed by Cox proportional hazards regression with patient characteristics (age, sex, and Mini-Mental State Examination [MMSE] score), magnetic resonance imaging (MRI) biomarkers (hippocampal volume, normalized whole-brain volume), cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, tau), and combined biomarkers. Data were analyzed from November 1, 2015, to October 1, 2016.Main Outcomes and Measures: Clinical end points were AD dementia and any type of dementia after 1 and 3 years.Results: Of the 525 patients, 210 (40.0{\%}) were female, and the mean (SD) age was 67.3 (8.4) years. On the basis of age, sex, and MMSE score only, the 3-year progression risk to AD dementia ranged from 26{\%} (95{\%} CI, 19{\%}-34{\%}) in younger men with MMSE scores of 29 to 76{\%} (95{\%} CI, 65{\%}-84{\%}) in older women with MMSE scores of 24 (1-year risk: 6{\%} [95{\%} CI, 4{\%}-9{\%}] to 24{\%} [95{\%} CI, 18{\%}-32{\%}]). Three- and 1-year progression risks were 86{\%} (95{\%} CI, 71{\%}-95{\%}) and 27{\%} (95{\%} CI, 17{\%}-41{\%}) when MRI results were abnormal, 82{\%} (95{\%} CI, 73{\%}-89{\%}) and 26{\%} (95{\%} CI, 20{\%}-33{\%}) when CSF test results were abnormal, and 89{\%} (95{\%} CI, 79{\%}-95{\%}) and 26{\%} (95{\%} CI, 18{\%}-36{\%}) when the results of both tests were abnormal. Conversely, 3- and 1-year progression risks were 18{\%} (95{\%} CI, 13{\%}-27{\%}) and 3{\%} (95{\%} CI, 2{\%}-5{\%}) after normal MRI results, 6{\%} (95{\%} CI, 3{\%}-9{\%}) and 1{\%} (95{\%} CI, 0.5{\%}-2{\%}) after normal CSF test results, and 4{\%} (95{\%} CI, 2{\%}-7{\%}) and 0.5{\%} (95{\%} CI, 0.2{\%}-1{\%}) after combined normal MRI and CSF test results. The prognostic value of models determining any type of dementia were in the same order of magnitude although somewhat lower. External validation in Alzheimer's Disease Neuroimaging Initiative 2 showed that our models were highly robust.Conclusions and Relevance: This study provides biomarker-based prognostic models that may help determine AD dementia and any type of dementia in patients with MCI at the individual level. This finding supports clinical decision making and application of biomarkers in daily practice.",
author = "{van Maurik}, {Ingrid S.} and Zwan, {Marissa D.} and Tijms, {Betty M.} and Bouwman, {Femke H.} and Teunissen, {Charlotte E.} and Philip Scheltens and Wattjes, {Mike P.} and Frederik Barkhof and Johannes Berkhof and {van der Flier}, {Wiesje M.} and {Alzheimer’s Disease Neuroimaging Initiative}",
year = "2017",
month = "12",
day = "1",
doi = "10.1001/jamaneurol.2017.2712",
language = "English",
volume = "74",
pages = "1481--1491",
journal = "JAMA Neurology",
issn = "2168-6149",
publisher = "American Medical Association",
number = "12",

}

TY - JOUR

T1 - Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project

AU - van Maurik, Ingrid S.

AU - Zwan, Marissa D.

AU - Tijms, Betty M.

AU - Bouwman, Femke H.

AU - Teunissen, Charlotte E.

AU - Scheltens, Philip

AU - Wattjes, Mike P.

AU - Barkhof, Frederik

AU - Berkhof, Johannes

AU - van der Flier, Wiesje M.

AU - Alzheimer’s Disease Neuroimaging Initiative

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Importance: Biomarkers do not determine conversion to Alzheimer disease (AD) perfectly, and criteria do not specify how to take patient characteristics into account. Consequently, biomarker use may be challenging for clinicians, especially in patients with mild cognitive impairment (MCI).Objective: To construct biomarker-based prognostic models that enable determination of future AD dementia in patients with MCI.Design, Setting, and Participants: This study is part of the Alzheimer's Biomarkers in Daily Practice (ABIDE) project. A total of 525 patients with MCI from the Amsterdam Dementia Cohort (longitudinal cohort, tertiary referral center) were studied. All patients had their baseline visit to a memory clinic from September 1, 1997, through August 31, 2014. Prognostic models were constructed by Cox proportional hazards regression with patient characteristics (age, sex, and Mini-Mental State Examination [MMSE] score), magnetic resonance imaging (MRI) biomarkers (hippocampal volume, normalized whole-brain volume), cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, tau), and combined biomarkers. Data were analyzed from November 1, 2015, to October 1, 2016.Main Outcomes and Measures: Clinical end points were AD dementia and any type of dementia after 1 and 3 years.Results: Of the 525 patients, 210 (40.0%) were female, and the mean (SD) age was 67.3 (8.4) years. On the basis of age, sex, and MMSE score only, the 3-year progression risk to AD dementia ranged from 26% (95% CI, 19%-34%) in younger men with MMSE scores of 29 to 76% (95% CI, 65%-84%) in older women with MMSE scores of 24 (1-year risk: 6% [95% CI, 4%-9%] to 24% [95% CI, 18%-32%]). Three- and 1-year progression risks were 86% (95% CI, 71%-95%) and 27% (95% CI, 17%-41%) when MRI results were abnormal, 82% (95% CI, 73%-89%) and 26% (95% CI, 20%-33%) when CSF test results were abnormal, and 89% (95% CI, 79%-95%) and 26% (95% CI, 18%-36%) when the results of both tests were abnormal. Conversely, 3- and 1-year progression risks were 18% (95% CI, 13%-27%) and 3% (95% CI, 2%-5%) after normal MRI results, 6% (95% CI, 3%-9%) and 1% (95% CI, 0.5%-2%) after normal CSF test results, and 4% (95% CI, 2%-7%) and 0.5% (95% CI, 0.2%-1%) after combined normal MRI and CSF test results. The prognostic value of models determining any type of dementia were in the same order of magnitude although somewhat lower. External validation in Alzheimer's Disease Neuroimaging Initiative 2 showed that our models were highly robust.Conclusions and Relevance: This study provides biomarker-based prognostic models that may help determine AD dementia and any type of dementia in patients with MCI at the individual level. This finding supports clinical decision making and application of biomarkers in daily practice.

AB - Importance: Biomarkers do not determine conversion to Alzheimer disease (AD) perfectly, and criteria do not specify how to take patient characteristics into account. Consequently, biomarker use may be challenging for clinicians, especially in patients with mild cognitive impairment (MCI).Objective: To construct biomarker-based prognostic models that enable determination of future AD dementia in patients with MCI.Design, Setting, and Participants: This study is part of the Alzheimer's Biomarkers in Daily Practice (ABIDE) project. A total of 525 patients with MCI from the Amsterdam Dementia Cohort (longitudinal cohort, tertiary referral center) were studied. All patients had their baseline visit to a memory clinic from September 1, 1997, through August 31, 2014. Prognostic models were constructed by Cox proportional hazards regression with patient characteristics (age, sex, and Mini-Mental State Examination [MMSE] score), magnetic resonance imaging (MRI) biomarkers (hippocampal volume, normalized whole-brain volume), cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, tau), and combined biomarkers. Data were analyzed from November 1, 2015, to October 1, 2016.Main Outcomes and Measures: Clinical end points were AD dementia and any type of dementia after 1 and 3 years.Results: Of the 525 patients, 210 (40.0%) were female, and the mean (SD) age was 67.3 (8.4) years. On the basis of age, sex, and MMSE score only, the 3-year progression risk to AD dementia ranged from 26% (95% CI, 19%-34%) in younger men with MMSE scores of 29 to 76% (95% CI, 65%-84%) in older women with MMSE scores of 24 (1-year risk: 6% [95% CI, 4%-9%] to 24% [95% CI, 18%-32%]). Three- and 1-year progression risks were 86% (95% CI, 71%-95%) and 27% (95% CI, 17%-41%) when MRI results were abnormal, 82% (95% CI, 73%-89%) and 26% (95% CI, 20%-33%) when CSF test results were abnormal, and 89% (95% CI, 79%-95%) and 26% (95% CI, 18%-36%) when the results of both tests were abnormal. Conversely, 3- and 1-year progression risks were 18% (95% CI, 13%-27%) and 3% (95% CI, 2%-5%) after normal MRI results, 6% (95% CI, 3%-9%) and 1% (95% CI, 0.5%-2%) after normal CSF test results, and 4% (95% CI, 2%-7%) and 0.5% (95% CI, 0.2%-1%) after combined normal MRI and CSF test results. The prognostic value of models determining any type of dementia were in the same order of magnitude although somewhat lower. External validation in Alzheimer's Disease Neuroimaging Initiative 2 showed that our models were highly robust.Conclusions and Relevance: This study provides biomarker-based prognostic models that may help determine AD dementia and any type of dementia in patients with MCI at the individual level. This finding supports clinical decision making and application of biomarkers in daily practice.

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U2 - 10.1001/jamaneurol.2017.2712

DO - 10.1001/jamaneurol.2017.2712

M3 - Article

VL - 74

SP - 1481

EP - 1491

JO - JAMA Neurology

JF - JAMA Neurology

SN - 2168-6149

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