Predicting conversion from mild cognitive impairment to Alzheimer's disease using neuropsychological tests and multivariate methods

Abstract

Behavioral markers measured through neuropsychological testing in mild cognitive impairment (MCI) were analyzed and combined in multivariate ways to predict conversion to Alzheimer's disease (AD) in a longitudinal study of 43 MCI patients. The test measures taken at a baseline evaluation were first reduced to underlying components (principal component analysis, PCA), and then the component scores were used in discriminant analysis to classify MCI individuals as likely to convert or not. When empirically weighted and combined, episodic memory, speeded executive functioning, recognition memory (false and true positives), visuospatial memory processing speed, and visuospatial episodic memory were together strong predictors of conversion to AD. These multivariate combinations of the test measures achieved through the PCA were good, statistically significant predictors of MCI conversion to AD (84% accuracy, 86% sensitivity, and 83% specificity). Importantly, the posterior probabilities of group membership that accompanied the binary prediction for each participant indicated the confidence of the prediction. Most of the participants (81%) were in the highly confident probability bins (.70–1.00), where the obtained prediction accuracy was more than 90%. The strength and reliability of this multivariate prediction method were tested by cross-validation and randomized resampling.

Keywords:

• Neuropsychological tests
• Predict
• Multivariate
• Alzheimer's disease
• Mild cognitive impairment
• Discriminant analysis
• Principal component analysis
• Posterior probability

Maria Guillily is now at the Department of Pharmacology and Experimental Therapeutics at Boston University. Tiffany Sandoval is now at the San Diego State University/University of California at San Diego Joint Doctoral Program in Clinical Psychology. Elizabeth DeGrush is now at the Chicago College of Osteopathic Medicine at Midwestern University. Lindsey Reilly is now at the Springer Publishing Company. We thank: the Memory Disorders Clinic at the University of Rochester Medical Center, Monroe Community Hospital, the Alzheimer's Disease Center, especially Paul Coleman, Charles Duffy, and Roger Kurlan, for their strong support of our research; Susan E. Chapman for help in writing; Robert Emerson and William Vaughn for their technical contributions; Courtney Vargas, Dustina Holt, Jonathan DeRight, Cendrine Robinson, Kristen Morie, Anna Fagan, Michael Garber-Barron, Leon Tsao, and Brittany Huber for technical help; and the many voluntary participants in this research. This research was supported by the National Institute of Health Grants P30-AG08665, R01-AG018880, and P30-EY01319.