Screening for preclinical Alzheimer's disease: Deriving optimal policies using a partially observable Markov model.

Alzheimer's Disease (AD) is believed to be the most common type of dementia. Even though screening for AD has been discussed widely, there is no screening program implemented as part of a policy in any country. Current medical research motivates focusing on the preclinical stages of the disease in a modeling initiative. We develop a partially observable Markov decision process model to determine optimal screening programs. The model contains disease free and preclinical AD partially observable states and the screening decision is taken while an individual is in one of those states. An observable diagnosed preclinical AD state is integrated along with observable mild cognitive impairment, AD and death states. Transition probabilities among states are estimated using data from Knight Alzheimer's Disease Research Center (KADRC) and relevant literature. With an objective of maximizing expected total quality-adjusted life years (QALYs), the output of the model is an optimal screening program that specifies at what points in time an individual over 50 years of age with a given risk of AD will be directed to undergo screening. The screening test used to diagnose preclinical AD has a positive disutility, is imperfect and its sensitivity and specificity are estimated using the KADRC data set. We study the impact of a potential intervention with a parameterized effectiveness and disutility on model outcomes for three different risk profiles (low, medium and high). When intervention effectiveness and disutility are at their best, the optimal screening policy is to screen every year between ages 50 and 95, with an overall QALY gain of 0.94, 1.9 and 2.9 for low, medium and high risk profiles, respectively. As intervention effectiveness diminishes and/or its disutility increases, the optimal policy changes to sporadic screening and then to never screening. Under several scenarios, some screening within the time horizon is optimal from a QALY perspective. Moreover, an in-depth analysis of costs reveals that implementing these policies are either cost-saving or cost-effective.