Verbal fluency predicts mortality in Alzheimer disease

Objectives: To assess the predictive value of neuropsychologic profiles, at diagnosis, for mortality in incident Alzheimer disease (AD). Background: Rate of AD progression varies significantly across individuals for reasons that are not well understood. Several studies have linked rapid decline with disproportionately impaired executive functioning, presumably reflecting greater impairment of frontal networks. To the extent that differential neuropsychologic profiles reflect various neuropathologic presentations of AD, such profiles may inform survival estimates early in the disease. Methods: Five neuropsychologic indices were used to characterize performance in 161 individuals at diagnosis of AD during a 15-year, longitudinal, primarily community-based study. Results: Fifty-two percent of participants reached the mortality end point with a median survival of 5.52 years (95% confidence interval, 4.41-6.63). Cox proportional hazards analyses indicated that older age at diagnosis was associated with higher risk of mortality (risk ratios, 1.08; 95% confidence interval, 1.04-1.12) whereas Hispanic ethnicity predicted lower mortality [0.22 (0.09-0.55)]. Controlling for these 2 demographic variables, higher verbal fluency scores at diagnosis predicted lower mortality [0.69 (0.49-0.96)]. Conclusions: Disproportionate impairment of both category and letter fluency at the earliest stages of AD predicts mortality. The prognostic value of these tests may derive from their general psychometric properties, or may reflect the measures' sensitivity to an early or critical level of compromise to frontal networks.