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. 2017 Dec 1;74(12):1481-1491.
doi: 10.1001/jamaneurol.2017.2712.

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

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

Ingrid S van Maurik et al. JAMA Neurol. .
Free PMC article

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Scheltens reported receiving grant support (for the institution) from GE Healthcare, Danone Research, Piramal, and Merck and, in the past 2 years, receiving consultancy/speaker fees (paid to the institution) from Lilly, GE Healthcare, Novartis, Sanofi, Nutricia, Probiodrug, Biogen, Roche, Avraham, and EIP Pharma. Dr Barkhof reported serving as a consultant for Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer Schering, Merck Serono, Roche, Novartis, Genzume, and Sanofi; receiving sponsorship from European Horizon 2020, Netherlands Organisation for Scientific Research, National Institute for Health Research–University College London Hospitals Biomedical Research Centre, Scottish Multiple Sclerosis Register, Teva, Novartis, and Toshiba; and serving on the editorial boards of Radiology, Brain, Neuroradiology, MSJ, and Neurology. Dr van der Flier reported performing contract research and serving as an invited speaker for Boehringer Ingelheim and working on research programs funded by ZonMW, Netherlands Organisation for Scientific Research, European 7th Framework Programme, Alzheimer Nederland, Cardiovasculair Onderzoek Nederland, stichting Dioraphte, Gieskes-Strijbis fonds, Boehringer Ingelheim, Piramal Neuroimaging, Roche BV, Janssen Stellar, and Combinostics (all funding is paid to her institution). No other disclosures were reported.

Figures

Figure.
Figure.. Probability Isographs for 1- and 3-Year Progression to Alzheimer Disease Dementia
Probability of conversion within 1 (A, C, E) and 3 (B, D, F) years based on amyloid-β1-42 (Aβ1-42) and tau stratified for normalized whole-brain volume (NWBV). Isographs are based on a mean hippocampal volume of 6.6 mL and a mean Mini-Mental State Examination score of 26.

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