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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

Personalized predictive modeling for patients with Alzheimer’s disease using an extension of Sullivan’s life table model

Authors: Eric Stallard, Bruce Kinosian, Yaakov Stern

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

Alzheimer’s disease (AD) progression varies substantially among patients, hindering calculation of residual total life expectancy (TLE) and its decomposition into disability-free life expectancy (DFLE) and disabled life expectancy (DLE) for individual patients with AD. The objective of the present study was to assess the accuracy of a new synthesis of Sullivan’s life table (SLT) and longitudinal Grade of Membership (L-GoM) models that estimates individualized TLEs, DFLEs, and DLEs for patients with AD. If sufficiently accurate, such information could enhance the quality of important decisions in AD treatment and patient care.

Methods

We estimated a new SLT/L-GoM model of the natural history of AD over 10 years in the Predictors 2 Study cohort: N = 229 with 6 fixed and 73 time-varying covariates over 21 examinations covering 11 measurement domains including cognitive, functional, behavioral, psychiatric, and other symptoms/signs. Total remaining life expectancy was censored at 10 years. Disability was defined as need for full-time care (FTC), the outcome most strongly associated with AD progression. All parameters were estimated via weighted maximum likelihood using data-dependent weights designed to ensure that the estimates of the prognostic subtypes were of high quality. Goodness of fit was tested/confirmed for survival and FTC disability for five relatively homogeneous subgroups defined to cover the range of patient outcomes over the 21 examinations.

Results

The substantial heterogeneity in initial patient presentation and AD progression was captured using three clinically meaningful prognostic subtypes and one terminal subtype exhibiting highly differentiated symptom severity on 7 of the 11 measurement domains. Comparisons of the observed and estimated survival and FTC disability probabilities demonstrated that the estimates were accurate for all five subgroups, supporting their use in AD life expectancy calculations. Mean 10-year TLE differed widely across subgroups: range 3.6–8.0 years, average 6.1 years. Mean 10-year DFLE differed relatively even more widely across subgroups: range 1.2–6.5 years, average 4.0 years. Mean 10-year DLE was relatively much closer: range 1.5–2.3 years, average 2.1 years.

Conclusions

The SLT/L-GoM model yields accurate maximum likelihood estimates of TLE, DFLE, and DLE for patients with AD; it provides a realistic, comprehensive modeling framework for endpoint and resource use/cost calculations.
Appendix
Available only for authorised users
Footnotes
1
Our prior analysis of Predictors 2 had N = 254 [7], but the study was ongoing. The final sample size was 267; of these, 38 were diagnosed as having Lewy body dementia at the intake examination and were excluded from the present analysis.
 
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Metadata
Title
Personalized predictive modeling for patients with Alzheimer’s disease using an extension of Sullivan’s life table model
Authors
Eric Stallard
Bruce Kinosian
Yaakov Stern
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0302-6

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