MODELING THE BENEFITS OF DELAYED ONSET OF MILD COGNITIVE IMPAIRMENT DUE TO ALZHEIMER'S DISEASE IN THE UNITED STATES

Purpose: Alzheimer's disease (AD) is a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Therapies that delay the onset of MCI due to AD could have significant implications on the trajectory of AD-related outcomes, including a reduction in the number of patients who require institutionalization. However, the impact of a delay in MCI due to AD has not been established, nor has progression through the entire disease continuum been fully characterized using transition probabilities. The objectives of this study were to: 1) estimate progression from normal cognition to MCI due to AD to mild/moderate/severe AD dementia, including the age-specific likelihood of institutionalization and death from each health state using a well-defined US population; and 2) develop a decision analysis model, using the study progression rates, to estimate the expected effect of delayed onset of MCI due to AD on AD-related outcomes for a US cohort.

Method : Longitudinal data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set, which contain annual clinical evaluations for subjects across the AD continuum, were utilized. The NACC database is funded by NIA/NIH Grant U01 AG016976. At each visit, patients were classified by health state based on clinical diagnosis, global Clinical Dementia Rating score, and primary etiologic diagnosis of cognitive impairment (CI) (Figure 1). Age-specific transitional probabilities of progression to each health state were estimated using a multivariate, ordered probit model, controlling for the patient's prior health state and current age. A separate multivariate regression model was used to assess the likelihood of institutionalization. Age-specific risk of death from each health state was derived using published estimates and life tables for the US population.

Result: When the observed transition probabilities are applied to a cohort of 100 normal-cognition patients at age 65 years, a 2-year delay in onset of MCI due to AD is, over a lifetime, predicted to avoid 4.4 cases of AD dementia, delay average time to AD onset (1.4 years), increase survival (0.26 years), increase time with normal cognition (0.75 years), and reduce time spent institutionalized (14%).

Conclusion: Therapies that delay the onset of MCI due to AD could have significant implications for rates of AD dementia and AD-associated institutionalization and death.