Individual growth curve analysis of APOE ε4-associated cognitive decline in Alzheimer disease

Background: The apolipoprotein E epsilon4 (APOE epsilon4) allele is associated with an increased risk of developing Alzheimer disease (AD). However, findings regarding an association between the APOE epsilon4 allele and the rate of decline in AD have been mixed. Objective: To examine the relationship between the APOE epsilon4 allele and the rate of cognitive and functional decline in AD using individual growth curve analyses. Design: Longitudinal cohort study. Setting: Alzheimer Disease Research Center at Baylor College of Medicine. Patients: A total of 189 patients meeting NINCDSADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria for probable AD at baseline who under-went annual follow-up evaluations for at least 2 years. Main Outcome Measures: Individual growth curve parameters derived from baseline and follow-up performance on global and specific measures of cognitive and functional abilities. Results: Patients with 2 APOE epsilon4 alleles exhibited a slower rate of decline on measures of global cognitive functioning and functional abilities. No significant association was detected between the APOE epsilon4 allele and the rate of decline on measures of specific cognitive functions. Conclusions: Although the APOE epsilon4 allele is associated with an increased risk of developing AD, it seems that having 2 APOE epsilon4 alleles is associated with a slower clinical course. These findings are consistent with hypotheses that the biological processes contributing to the onset of AD are different from those involved in determining its clinical course.