Timing of onset and rate of decline in learning and retention in the pre-dementia phase of Alzheimer's disease

Objective: To examine trajectories of declines in learning and retention during the predementia phase of Alzheimer's disease (AD) using the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR). Method: Learning was defined by the sum of free recall over three test trials. Retention was defined in two ways: by delayed free recall (DFR) and by savings; DFR adjusted for learning. The performances of 217 incident AD cases from the Baltimore Longitudinal Study of Aging (BLSA) were aligned based on the time that AD was first diagnosed. The predementia phase of learning and retention decline was assessed using change point models in which cognitive trajectories are described by a series of linear components with knots delineating times of accelerating decline. Results: Trajectories for both learning and DFR had two change points: the first at 6.58 (95% confidence intervals (CI): 6.56, 6.60) to 7.29 (95% CI: 6.13, 8.46) years before diagnosis followed by gradual decline over the next 4 years, and a second acceleration of decline 1.89 (0.56, 3.24) to 2.93 (95% CI: 1.56, 4.30) years before diagnosis. The change points for DFR were not significantly earlier in the predementia phase than the change points for learning. Savings had one change point, 5.3 (95% CI: 3.56, 7.04) years before diagnosis. Conclusion: Both learning and DFR showed similar profiles of decline in the years prior to the clinical diagnosis of AD. When delayed recall was adjusted for initial learning, the measure was less sensitive to early disease.