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Alzheimer's disease progression model based on integrated biomarkers and clinical measures.

Qiu Y, Li L, Zhou TY, Lu W, Alzheimer's Disease Neuroimaging Initiati - Acta Pharmacol. Sin. (2014)

Bottom Line: Biomarkers and image markers of Alzheimer's disease (AD), such as cerebrospinal fluid Aβ42 and p-tau, are effective predictors of cognitive decline or dementia.The most likely models for the Ratio, hippocampal volume, and ADAS-cog (logistic, Emax, and linear models, respectively) were used to construct the final model.Baseline disease state had an impact on all the 3 endpoints (the Ratio, hippocampal volume, and ADAS-cog), while APOEε4 genotype and age only influence the Ratio and hippocampal volume.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Beijing 100191, China [2] Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.

ABSTRACT

Aim: Biomarkers and image markers of Alzheimer's disease (AD), such as cerebrospinal fluid Aβ42 and p-tau, are effective predictors of cognitive decline or dementia. The aim of this study was to integrate these markers with a disease progression model and to identify their abnormal ranges.

Methods: The data of 395 participants, including 86 normal subjects, 108 early mild cognitive impairment (EMCI) subjects, 120 late mild cognitive impairment (LMCI) subjects, and 81 AD subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For the participants, baseline and long-term data on cerebrospinal fluid Aβ42 and p-tau, hippocampal volume, and ADAS-cog were available. Various linear and nonlinear models were tested to determine the associations among the ratio of Aβ42 to p-tau (the Ratio), hippocampal volume and ADAS-cog.

Results: The most likely models for the Ratio, hippocampal volume, and ADAS-cog (logistic, Emax, and linear models, respectively) were used to construct the final model. Baseline disease state had an impact on all the 3 endpoints (the Ratio, hippocampal volume, and ADAS-cog), while APOEε4 genotype and age only influence the Ratio and hippocampal volume.

Conclusion: The Ratio can be used to identify the disease stage for an individual, and clinical measures integrated with the Ratio improve the accuracy of mild cognitive impairment (MCI) to AD conversion forecasting.

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Related in: MedlinePlus

Visual predictive check from 1000 simulations. The solid line represents the median observed data, and the gray field around it represents a simulation-based 95% confidence interval for the median. The observed 5% and 95% percentiles are presented with dashed lines, and the gray fields around them are their 95% confidence intervals. The observed data are represented by circles.
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fig3: Visual predictive check from 1000 simulations. The solid line represents the median observed data, and the gray field around it represents a simulation-based 95% confidence interval for the median. The observed 5% and 95% percentiles are presented with dashed lines, and the gray fields around them are their 95% confidence intervals. The observed data are represented by circles.

Mentions: The results of VPC, show that the distribution of the observed data was contained within the empirical distribution of the estimates predicted by the final model over 1000 simulations. This indicates that the final model prediction was reasonable for both the point estimates as well as the distributions (Figure 3).


Alzheimer's disease progression model based on integrated biomarkers and clinical measures.

Qiu Y, Li L, Zhou TY, Lu W, Alzheimer's Disease Neuroimaging Initiati - Acta Pharmacol. Sin. (2014)

Visual predictive check from 1000 simulations. The solid line represents the median observed data, and the gray field around it represents a simulation-based 95% confidence interval for the median. The observed 5% and 95% percentiles are presented with dashed lines, and the gray fields around them are their 95% confidence intervals. The observed data are represented by circles.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4155529&req=5

fig3: Visual predictive check from 1000 simulations. The solid line represents the median observed data, and the gray field around it represents a simulation-based 95% confidence interval for the median. The observed 5% and 95% percentiles are presented with dashed lines, and the gray fields around them are their 95% confidence intervals. The observed data are represented by circles.
Mentions: The results of VPC, show that the distribution of the observed data was contained within the empirical distribution of the estimates predicted by the final model over 1000 simulations. This indicates that the final model prediction was reasonable for both the point estimates as well as the distributions (Figure 3).

Bottom Line: Biomarkers and image markers of Alzheimer's disease (AD), such as cerebrospinal fluid Aβ42 and p-tau, are effective predictors of cognitive decline or dementia.The most likely models for the Ratio, hippocampal volume, and ADAS-cog (logistic, Emax, and linear models, respectively) were used to construct the final model.Baseline disease state had an impact on all the 3 endpoints (the Ratio, hippocampal volume, and ADAS-cog), while APOEε4 genotype and age only influence the Ratio and hippocampal volume.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Beijing 100191, China [2] Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.

ABSTRACT

Aim: Biomarkers and image markers of Alzheimer's disease (AD), such as cerebrospinal fluid Aβ42 and p-tau, are effective predictors of cognitive decline or dementia. The aim of this study was to integrate these markers with a disease progression model and to identify their abnormal ranges.

Methods: The data of 395 participants, including 86 normal subjects, 108 early mild cognitive impairment (EMCI) subjects, 120 late mild cognitive impairment (LMCI) subjects, and 81 AD subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For the participants, baseline and long-term data on cerebrospinal fluid Aβ42 and p-tau, hippocampal volume, and ADAS-cog were available. Various linear and nonlinear models were tested to determine the associations among the ratio of Aβ42 to p-tau (the Ratio), hippocampal volume and ADAS-cog.

Results: The most likely models for the Ratio, hippocampal volume, and ADAS-cog (logistic, Emax, and linear models, respectively) were used to construct the final model. Baseline disease state had an impact on all the 3 endpoints (the Ratio, hippocampal volume, and ADAS-cog), while APOEε4 genotype and age only influence the Ratio and hippocampal volume.

Conclusion: The Ratio can be used to identify the disease stage for an individual, and clinical measures integrated with the Ratio improve the accuracy of mild cognitive impairment (MCI) to AD conversion forecasting.

Show MeSH
Related in: MedlinePlus