Dataset Information

The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.

ABSTRACT:

Introduction

We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates.

Methods

We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers.

Results

In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers.

Discussion

Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.

SUBMITTER: Bertens D

PROVIDER: S-EPMC5671625 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.

Bertens Daniela D Tijms Betty M BM Vermunt Lisa L Prins Niels D ND Scheltens Philip P Visser Pieter Jelle PJ

Alzheimer's & dementia (New York, N. Y.) 20170921 4

<h4>Introduction</h4>We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates.<h4>Methods</h4>We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or p ...[more]

PMID: 29124109

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Project description:Biomarkers useful for the predementia stages of Alzheimer's disease are needed. Electroencephalography and magnetoencephalography (MEG) are expected to provide potential biomarker candidates for evaluating the predementia stages of Alzheimer's disease. However, the physiological relevance of EEG/MEG signal changes and their role in pathophysiological processes such as amyloid-β deposition and neurodegeneration need to be elucidated. We evaluated 28 individuals with mild cognitive impairment and 38 cognitively normal individuals, all of whom were further classified into amyloid-β-positive mild cognitive impairment (n = 17, mean age 74.7 ± 5.4 years, nine males), amyloid-β-negative mild cognitive impairment (n = 11, mean age 73.8 ± 8.8 years, eight males), amyloid-β-positive cognitively normal (n = 13, mean age 71.8 ± 4.4 years, seven males), and amyloid-β-negative cognitively normal (n = 25, mean age 72.5 ± 3.4 years, 11 males) individuals using Pittsburgh compound B-PET. We measured resting state MEG for 5 min with the eyes closed, and investigated regional spectral patterns of MEG signals using atlas-based region of interest analysis. Then, the relevance of the regional spectral patterns and their associations with pathophysiological backgrounds were analysed by integrating information from Pittsburgh compound B-PET, fluorodeoxyglucose-PET, structural MRI, and cognitive tests. The results demonstrated that regional spectral patterns of resting state activity could be separated into several types of MEG signatures as follows: (i) the effects of amyloid-β deposition were expressed as the alpha band power augmentation in medial frontal areas; (ii) the delta band power increase in the same region was associated with disease progression within the Alzheimer's disease continuum and was correlated with entorhinal atrophy and an Alzheimer's disease-like regional decrease in glucose metabolism; and (iii) the global theta power augmentation, which was previously considered to be an Alzheimer's disease-related EEG/MEG signature, was associated with general cognitive decline and hippocampal atrophy, but was not specific to Alzheimer's disease because these changes could be observed in the absence of amyloid-β deposition. The results suggest that these MEG signatures may be useful as unique biomarkers for the predementia stages of Alzheimer's disease.

Project description:BACKGROUND:The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown. OBJECTIVES:We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects. METHODS:We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups. RESULTS:Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r = 0.33, P < .001); furthermore, all other correlations between inflammatory markers were approximately 0, including correlations with sputum eosinophil counts. In addition, the predictive value of each biomarker alone or in combination was poor in obese subjects. In fact, in obese subjects none of the biomarkers of inflammation significantly predicted the presence of high sputum eosinophil counts. Obese asthmatic subjects have lower cut points for IgE levels (268 IU), fraction of exhaled nitric oxide values (14.5 ppb), and blood eosinophil counts (96 cells/?L) than all other groups. CONCLUSIONS:In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects.

Dataset Information

The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.

Introduction

Methods

Results

Discussion

Publications

The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.

Similar Datasets

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