title: Hypothesis testing of a change point during cognitive decline among Alzheimer's disease patients.
abstract: In this paper, we present a statistical hypothesis test for detecting a change point over the course of cognitive decline among Alzheimer's disease patients. The model under the null hypothesis assumes a constant rate of cognitive decline over time and the model under the alternative hypothesis is a general bilinear model with an unknown change point. When the change point is unknown, however, the null distribution of the test statistics is not analytically tractable and has to be simulated by parametric bootstrap. When the alternative hypothesis that a change point exists is accepted, we propose an estimate of its location based on the Akaike's Information Criterion. We applied our method to a data set from the Neuropsychological Database Initiative by implementing our hypothesis testing method to analyze Mini Mental Status Exam scores based on a random-slope and random-intercept model with a bilinear fixed effect. Our result shows that despite large amount of missing data, accelerated decline did occur for MMSE among AD patients. Our finding supports the clinical belief of the existence of a change point during cognitive decline among AD patients and suggests the use of change point models for the longitudinal modeling of cognitive decline in AD research.
authors.affiliation: Division of Epidemiology and Bisotatistics, Graduate School of Public Health, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182-4162, USA. mji@mail.sdsu.edu
authors.forename: Ming
authors.initials: M
authors.lastname: Ji
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D015982:Bias; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008432:Mathematical Computing; D008609:Mental Status Schedule / Q000706:statistics & numerical data*; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D011594:Psychometrics / Q000706:statistics & numerical data