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

摘要

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. 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. 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. 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.