Risk Stratification Using Cerebrospinal Fluid Biomarkers in Patients with Mild Cognitive Impairment: An Exploratory Analysis

Tzeyu L Michaud; Robert L Kane; J Riley McCarten; Joseph E Gaugler; John A Nyman; Karen M Kuntz; Alzheimer’s Disease Neuroimaging Initiative

doi:10.3233/JAD-150066

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Risk Stratification Using Cerebrospinal Fluid Biomarkers in Patients with Mild Cognitive Impairment: An Exploratory Analysis

Journal article

Peer reviewed

Risk Stratification Using Cerebrospinal Fluid Biomarkers in Patients with Mild Cognitive Impairment: An Exploratory Analysis

Tzeyu L Michaud, Robert L Kane, J Riley McCarten, Joseph E Gaugler, John A Nyman, Karen M Kuntz and Alzheimer’s Disease Neuroimaging Initiative

Journal of Alzheimer's disease, Vol.47(3), pp.729-740

2015

DOI: 10.3233/JAD-150066

PMCID: PMC6342191

PMID: 26401707

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https://www.ncbi.nlm.nih.gov/pmc/articles/6342191View

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Abstract

Cerebrospinal fluid (CSF) biomarkers can distinguish Alzheimer's disease (AD) patients from normal controls; however, their interpretation and potential for use in patients with mild cognitive impairment (MCI) remains unclear. To examine whether biomarker levels allow for risk stratification among MCI patients who are at increased risk to develop AD, thus allowing for improved targeting of early interventions for those whose risk are higher. We analyzed data from the Alzheimer's Disease Neuroimaging Initiative on MCI patients (n = 195) to estimate their risk of developing AD for up to 6 years on the basis of baseline CSF biomarkers. We used time-dependent receiver operating characteristic analysis to identify the best combination of biomarkers to discriminate those who converted to AD from those who remained stable. We used these data to construct a multi-biomarker score and estimated the risk of progression to AD for each quintile of the multi-biomarker score. We found that Aβ(1-42) and P-tau(181p) were the best combination among CSF biomarkers to predict the overall risk of developing AD among MCI patients (area under the curve = 0.77). The hazard ratio of developing AD among MCI patients with high-risk (3rd-5th quintiles) biomarker levels was about 4 times greater than MCI patients with low-risk (1st quintile) levels (95% confidence interval, 1.93-7.26). Our study identifies MCI patients at increased risk of developing AD by applying a multi-biomarker score using CSF biomarker results. Our findings may be of value to MCI patients and their clinicians for planning purposes and early intervention as well as for future clinical trials.

Peptide Fragments - cerebrospinal fluid

Prognosis

Area Under Curve

Humans

Male

Risk

tau Proteins - cerebrospinal fluid

Cognitive Dysfunction - cerebrospinal fluid

Alzheimer Disease - cerebrospinal fluid

Disease Progression

Alzheimer Disease - diagnosis

Aged, 80 and over

Amyloid beta-Peptides - cerebrospinal fluid

Female

Aged

Cognitive Dysfunction - diagnosis

Biomarkers - cerebrospinal fluid

Databases, Factual

Details

Title: Subtitle: Risk Stratification Using Cerebrospinal Fluid Biomarkers in Patients with Mild Cognitive Impairment: An Exploratory Analysis
Creators: Tzeyu L Michaud - Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Robert L Kane - Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
J Riley McCarten - Departments of Neurology and Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
Joseph E Gaugler - School of Nursing & Center on Aging, University of Minnesota, Minneapolis, MN, USA
John A Nyman - Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Karen M Kuntz - Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Alzheimer’s Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Journal of Alzheimer's disease, Vol.47(3), pp.729-740
DOI: 10.3233/JAD-150066
PMID: 26401707
PMCID: PMC6342191
NLM abbreviation: J Alzheimers Dis
ISSN: 1387-2877
eISSN: 1875-8908
Publisher: Netherlands
Grant note: Canadian Institutes of Health Research P30 AG013846 / NIA NIH HHS P01 AG003991 / NIA NIH HHS U01 AG024904 / NIA NIH HHS
Language: English
Date published: 2015
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051794902771

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