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

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Abstract

Objective

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.

Methods

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 ε4 carrier, education, duration of disease, cognitive level, pre-treatment progression rate (in MMSE) and the levels of the CSF biomarkers Aβ42, T-tau and P-tau.

Results

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.

Conclusion

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.

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