Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease

Abstract The heterogeneity of Alzheimer’s disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering alg...

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Autores principales:	Dragan Gamberger, Nada Lavrač, Shantanu Srivatsa, Rudolph E. Tanzi, P. Murali Doraiswamy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fce1100c1324e30be2bdb1cd214408a
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spelling	oai:doaj.org-article:6fce1100c1324e30be2bdb1cd214408a2021-12-02T16:06:17ZIdentification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease10.1038/s41598-017-06624-y2045-2322https://doaj.org/article/6fce1100c1324e30be2bdb1cd214408a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06624-yhttps://doaj.org/toc/2045-2322Abstract The heterogeneity of Alzheimer’s disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering algorithm. The algorithm identified homogenous clusters of MCI subjects with markedly different prognostic cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184 slow decliners. A classifier for identifying rapid decliners in one study showed high sensitivity and specificity in the second study. Characterizing subgroups of at risk subjects, with diverse prognostic outcomes, may provide novel mechanistic insights and facilitate clinical trials of drugs to delay the onset of AD.Dragan GambergerNada LavračShantanu SrivatsaRudolph E. TanziP. Murali DoraiswamyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dragan Gamberger Nada Lavrač Shantanu Srivatsa Rudolph E. Tanzi P. Murali Doraiswamy Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease
description	Abstract The heterogeneity of Alzheimer’s disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering algorithm. The algorithm identified homogenous clusters of MCI subjects with markedly different prognostic cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184 slow decliners. A classifier for identifying rapid decliners in one study showed high sensitivity and specificity in the second study. Characterizing subgroups of at risk subjects, with diverse prognostic outcomes, may provide novel mechanistic insights and facilitate clinical trials of drugs to delay the onset of AD.
format	article
author	Dragan Gamberger Nada Lavrač Shantanu Srivatsa Rudolph E. Tanzi P. Murali Doraiswamy
author_facet	Dragan Gamberger Nada Lavrač Shantanu Srivatsa Rudolph E. Tanzi P. Murali Doraiswamy
author_sort	Dragan Gamberger
title	Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease
title_short	Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease
title_full	Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease
title_fullStr	Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease
title_full_unstemmed	Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease
title_sort	identification of clusters of rapid and slow decliners among subjects at risk for alzheimer’s disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6fce1100c1324e30be2bdb1cd214408a
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Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease

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