Dataset Information

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer's disease.

ABSTRACT: The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the "progressive" MCI group (n =?46; mean time to progression 17?±?9.73 months) and (ii) the "stable" MCI group (n =?75; mean time of follow-up 31.37?±?14.58 months). Kaplan-Meier survival analyses were applied to explore each variable's relationship with the progression to AD. Once potential predictors were detected, Cox regression analyses were utilized to calculate a parsimonious model to estimate differences in time to progression. The final model included three variables (in order of relevance): left parahippocampal volume (corrected by intracranial volume, LP_ ICV), delayed recall (DR), and left inferior occipital lobe individual alpha peak frequency (LIOL_IAPF). Those MCIs with LP_ICV volume, DR score, and LIOL_IAPF value lower than the defined cutoff had 6 times, 5.5 times, and 3 times higher risk of progression to AD, respectively. Besides, when the categories of the three variables were "unfavorable" (i.e., values below the cutoff), 100% of cases progressed to AD at the end of follow-up. Our results highlighted the relevance of neurophysiological markers as predictors of conversion (LIOL_IAPF) and the importance of multivariate models that combine markers of different nature to predict time to progression from MCI to dementia.

SUBMITTER: Lopez ME

PROVIDER: S-EPMC7732920 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A multivariate model of time to conversion from mild cognitive impairment to Alzheimer's disease.

López María Eugenia ME Turrero Agustín A Cuesta Pablo P Rodríguez-Rojo Inmaculada Concepción IC Barabash Ana A Marcos Alberto A Maestú Fernando F Fernández Alberto A

GeroScience 20200904 6

The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the "progressive" MCI group (n = 46; mean time to progression 17 ± 9.73 months) and (ii) ...[more]

PMID: 32886293

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Project description:Multiple biomarkers can capture different facets of Alzheimer's disease. However, statistical models of biomarkers to predict outcomes in Alzheimer's rarely model nonlinear interactions between these measures. Here, we used Gaussian Processes to address this, modelling nonlinear interactions to predict progression from mild cognitive impairment (MCI) to Alzheimer's over 3 years, using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Measures included: demographics, APOE4 genotype, CSF (amyloid-β42, total tau, phosphorylated tau), [18F ]florbetapir, hippocampal volume and brain-age. We examined: (a) the independent value of each biomarker; and (b) whether modelling nonlinear interactions between biomarkers improved predictions. Each measured added complementary information when predicting conversion to Alzheimer's. A linear model classifying stable from progressive MCI explained over half the variance (R2 = 0.51, p < .001); the strongest independently contributing biomarker was hippocampal volume (R2 = 0.13). When comparing sensitivity of different models to progressive MCI (independent biomarker models, additive models, nonlinear interaction models), we observed a significant improvement (p < .001) for various two-way interaction models. The best performing model included an interaction between amyloid-β-PET and P-tau, while accounting for hippocampal volume (sensitivity = 0.77, AUC = 0.826). Closely related biomarkers contributed uniquely to predict conversion to Alzheimer's. Nonlinear biomarker interactions were also implicated, and results showed that although for some patients adding additional biomarkers may add little value (i.e., when hippocampal volume is high), for others (i.e., with low hippocampal volume) further invasive and expensive examination may be warranted. Our framework enables visualisation of these interactions, in individual patient biomarker 'space', providing information for personalised or stratified healthcare or clinical trial design.

Dataset Information

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer's disease.

Publications

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer's disease.

Similar Datasets

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