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Plasma phospholipids identify antecedent memory impairment in older adults.

ABSTRACT: Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-? levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.

SUBMITTER: Mapstone M

PROVIDER: S-EPMC5360460 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Plasma phospholipids identify antecedent memory impairment in older adults.

Mapstone Mark M Cheema Amrita K AK Fiandaca Massimo S MS Zhong Xiaogang X Mhyre Timothy R TR MacArthur Linda H LH Hall William J WJ Fisher Susan G SG Peterson Derick R DR Haley James M JM Nazar Michael D MD Rich Steven A SA Berlau Dan J DJ Peltz Carrie B CB Tan Ming T MT Kawas Claudia H CH Federoff Howard J HJ

Nature medicine 20140309 4

Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, curre ...[more]

PMID: 24608097

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Project description:There has been a growing interest in using computerized cognitive assessment to detect age-related cognitive disorders. We have developed a tablet-based cancellation test (e-CT), previously shown as a reliable measure of executive functions and free of effect of familiarity with computer-based devices in healthy older adults. This study aimed to investigate the influence of demographics and current daily use of computer-based devices in older adults with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). We further studied the ability of the e-CT to discriminate MCI and AD patients from older adults with normal cognition (NC).The e-CT was administered to 325 older adults (NC = 112, MCI = 129, AD = 84). Subjects also performed the K-T test, a paper-and-pencil cancellation test from which the e-CT was developed. Multiple linear regression analyses were conducted to assess the contribution of demographics and current daily use of computer-based devices on the e-CT in patient groups. The Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) were established to compare the efficacy of the e-CT and the K-T test to classify subjects into diagnostic groups.In the MCI group, age (B = -0.37, p<0.001) and current daily use of computer-based devices (B = 5.85, p<0.001) were associated with the number of correct cancellations of the e-CT. In the AD group, only current daily use of a computer-based device was a significant contributor (B = 6.28, p<0.001). The e-CT (AUC = 0.811; 95% confidence interval [CI]: 0.756-0.867) and the K-T (AUC = 0.837; CI: 0.787-0.887) showed good and comparable diagnostic accuracy to discriminate between MCI and NC subjects. To discriminate between NC and AD, both tests showed high diagnostic accuracy, with the AUC values of 0.923 (CI: 0.876-0.971) and 0.929 (95%CI: 0.886-0.972) for the e-CT and the K-T, respectively.The e-CT presents satisfying discriminative validity and is a promising tool for detection of early cognitive impairment in older adults.

Dataset Information

Plasma phospholipids identify antecedent memory impairment in older adults.

Publications

Plasma phospholipids identify antecedent memory impairment in older adults.

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