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Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project.
JAMA Neurol. 2017 12 01; 74(12):1481-1491.JN

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.

Authors+Show Affiliations

Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands. Department of Epidemiology and Biostatistics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands. Institutes of Neurology and Healthcare Engineering, University College London, London, England.Department of Epidemiology and Biostatistics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands. Department of Epidemiology and Biostatistics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

29049480

Citation

van Maurik, Ingrid S., et al. "Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project." JAMA Neurology, vol. 74, no. 12, 2017, pp. 1481-1491.
van Maurik IS, Zwan MD, Tijms BM, et al. Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project. JAMA Neurol. 2017;74(12):1481-1491.
van Maurik, I. S., Zwan, M. D., Tijms, B. M., Bouwman, F. H., Teunissen, C. E., Scheltens, P., Wattjes, M. P., Barkhof, F., Berkhof, J., & van der Flier, W. M. (2017). Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project. JAMA Neurology, 74(12), 1481-1491. https://doi.org/10.1001/jamaneurol.2017.2712
van Maurik IS, et al. Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project. JAMA Neurol. 2017 12 1;74(12):1481-1491. PubMed PMID: 29049480.
* Article titles in AMA citation format should be in sentence-case
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 - ,, PY - 2017/10/20/pubmed PY - 2017/12/27/medline PY - 2017/10/20/entrez SP - 1481 EP - 1491 JF - JAMA neurology JO - JAMA Neurol VL - 74 IS - 12 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. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/29049480/Interpreting_Biomarker_Results_in_Individual_Patients_With_Mild_Cognitive_Impairment_in_the_Alzheimer's_Biomarkers_in_Daily_Practice__ABIDE__Project_ DB - PRIME DP - Unbound Medicine ER -