Effects of a Non-focal Plasticity Protocol on Apathy in Moderate Alzheimer's Disease: A Randomized, Double-blind, Sham-controlled Trial

Abstract

BackgroundApathy is the most common neuropsychiatric symptom in Alzheimer's disease (AD) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions. To date no effective treatment for apathy has been demonstrated. ObjectiveWe aimed to investigate the effects and safety of repetitive transcranial direct current stimulation (tDCS) on apathy in moderate AD patients. MethodsForty patients were randomized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex (DLPFC). Patients received six sessions of intervention during 2 weeks and were evaluated at baseline, at week 1 and 2, and after 1 week without intervention. Clinical raters, patients, and caregivers were blinded. The primary outcome was apathy. Global cognition and neuropsychiatric symptoms were examined as secondary outcomes. ResultsThe mean MMSE score at baseline was 15.2 ± 2.9 and the mean Apathy Scale score was 27.7 ± 6.7. Changes on apathy scores over time were not different between active and sham tDCS (P = 0.552 for repeated measures). Further analyses confirm that changes from baseline did not differ between groups after the sixth session (active tDCS −1.95 (95%CI −3.49, −0.41); sham-tDCS −2.05 (95%CI −3.68, −0.42); P = 0.989]. Similarly, tDCS had no effect on secondary outcomes (P > 0.40). tDCS was well tolerated and not associated with significant adverse effects. ConclusionIn this adequately powered study for minimal clinically significant difference, our findings show that using the parameters we chose for this study, repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD.