Speech-related parameters are sensitive measures of acetylcholinesterase inhibitor therapy in mild Alzheimer’s disease

Our aim was to find out whether speech-related temporal parameters (SRTPs) are sensitive indicators of the clinical outcome in acetylcholinesterase (AChE) inhibitor therapy with donepezil, compared to the standard cognitive Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) used in clinical trials. In this 24-week-long, naturalistic, self-control, open-labeled, prospective pilot study with 10 mg donepezil on 20 mild AD patients, cognitive functions were evaluated using 15 different SRTPs analyzed by automatic speech recognition in the Speech-Gap Test® compared to ADAS-Cog test results. Among the SRTPs, the filled pause duration ratio significantly improved after 12 weeks of donepezil treatment. During the 24-week follow-up, additional SRTPs such as the filled pause count ratio and the filled pause frequency showed significant benefits. ADAS-Cog total scores showed a slight but not significant improvement compared to baseline after 12 and 24 weeks of donepezil treatment. Among the ADAS-Cog subtests, only orientation improved significantly after 24 weeks of donepezil treatment. Our results indicate that subtle changes in SRTPs measured by the Speech-Gap Test® could be considered as sensitive indicators of the efficacy of the pharmacotherapy in mild AD. According to our data, other cognitive domains did not show improvement in response to donepezil therapy rating by ADAS-Cog. Based on all of this, it is likely that examining and evaluating speech parameters may play an important role in determining the effects of pharmacological treatment of mild AD. The novelty of our study is that it applies the measurement of linguistic parameters as primary outcomes during a drug trial of mild AD in scientific research for the first time.