Higher Working Memory Predicts Slower Functional Decline in Autopsy-Confirmed Alzheimer's Disease

Abstract

Background: There is heterogeneity in the pattern of early cognitive deficits in Alzheimer's disease (AD). However, whether the severity of initial cognitive deficits relates to different clinical trajectories of AD progression is unclear. Objective: To determine if deficits in specific cognitive domains at the initial visit relate to the rate of progression in clinical trajectories of AD dementia. Methods: 68 subjects from the National Alzheimer's Coordinating Center database who had autopsy-confirmed AD as the primary diagnosis and at least 3 serial assessments a year apart, with a Mini-Mental State Examination (MMSE) score >15 and a Clinical Dementia Rating Scale-Global (CDR-G) score ≤1 at the initial visit were included. A mixed regression model was used to examine the association between initial neuropsychological performance and rate of change on the MMSE and CDR Sum of Boxes. Results: Preservation of working memory, but not episodic memory, in the mild cognitive impairment and early dementia stages of AD relates to slower rate of functional decline. Discussion: These findings are relevant for estimating the rate of decline in AD clinical trials and in counseling patients and families. Improving working memory performance as a possible avenue to decrease the rate of functional decline in AD dementia warrants closer investigation.