The clinical picture of Alzheimer's disease in the decade before diagnosis: Clinical and biomarker trajectories

Abstract

Objective: Increasing evidence suggests that Alzheimer's disease begins at least a decade before the diagnosis of dementia. Earlier identification of the disease will have important implications for intervention; however, current models of preclinical changes are theoretical and require verification from empirical observations. Furthermore, these models have not incorporated psychiatric features. Method: Clinical and biological markers were examined at baseline (1999-2001) in 9,076 people aged 65 years and older. A nested case-control study included 830 cases with Alzheimer's disease diagnosed by DSM-IV criteria during the 10-year follow-up and twice as many controls. By taking the distance between baseline and diagnosis as the length of the preclinical period, disease marker trajectories were estimated using nonparametric locally weighted smoothing analysis. Results: Significant differences for the cases compared to the controls were observed on both intercept and slope for truncated amyloid β40 (P =.006; P =.003, respectively), C-reactive protein (P =.03; P =.05), verbal fluency (P