Can CSF biomarkers or pre‐treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?

Abstract

The main objective of this study was to investigate possible predictors of response to cholinesterase inhibitor (ChEI) treatment, including pre-treatment progression rates and levels of the cerebrospinal fluid (CSF) biomarkers. A secondary objective was to evaluate whether treatment with ChEI changed progression. Out-patient individuals (n = 191) with the clinical diagnosis of Alzheimer's disease received ChEI treatment and were part of the Swedish Alzheimer Treatment Study (SATS), a prospective, longitudinal, non-randomised study in a routine clinical setting. Patients were assessed with MMSE, ADAS-cog and a global rating (CIBIC) at baseline, 2 months and every 6 months for a total period of 3 years. The following potential predictors of treatment response were investigated: age, gender, APOE epsilon 4 carrier, education, duration of disease, cognitive level, pre-treatment progression rate (in MMSE) and the levels of the CSF biomarkers A beta 42, T-tau and P-tau. Fast pre-treatment progression rate was a predictor of treatment response even after adjusting for baseline severity, another positive predictor of response. Patients in the fastest quartile of pre-treatment progression rates were significantly more prone to be responders at 2 months (adjusted OR 6.6, p = 0.001) and 6 months (adjusted OR 10.4, p < 0.001) than those in the slowest progressing quartile. Moreover, the linearity of progression was significantly changed by ChEI treatment at 6 months compared to the pre-treatment period. The rate of pre-treatment progression was the most consistent positive predictor of ChEI treatment response in the routine clinical setting. The progression rate was significantly changed by ChEI treatment.