Effects of anodal transcranial direct current stimulation on cognitive dysfunction in patients with progressive supranuclear palsy.

Abstract

Progressive supranuclear palsy (PSP) is a tauopathy characterized by motor, neurobehavioral and disabling brainstem deficits. No disease-modifying therapeutic options exist. The therapeutic potential of transcranial direct current stimulation (tDCS) has been highlighted in studies on patients with other neurodegenerative diseases. Therefore, by drawing upon the limited tDCS literature on PSP, we conducted a pilot study in order to evaluate the effect of tDCS over motor and premotor cortex in patients with PSP, with a particular emphasis on cognitive dysfunction. Eight patients affected by PSP were included (4 males and 4 females with mean age 67.4±7.4 years, range: 55-80 years and mean disease duration: 4.6±3.3 years, range: 1-11 years). The mean Unified Parkinson's Disease Rating Scale Part III (UPDRS III) was 49±16.1 and the mean Hoehn & Yahr (H&Y) scale was 3.9±1 at baseline. All pharmacological treatments (L-dopa, pramipexole, rotigotine, rasagiline, amantadine) were maintained stable during the study. We aimed at evaluating along with the motor outcome (as it is reflected on a disease-specific rating scale), the post-tDCS cognitive status after the completion of the intervention. The clinical evaluation involved the PSP-Rating Scale, the UPDRS III and the Timed Up and Go test. Neuropsychological assessment focused on auditory-verbal memory and learning, episodic memory, visuo-motor coordination and speed of information processing, executive functions and verbal fluency (phonemic and semantic). Anodal tDCS was applied over primary motor and pre-motor cortices in 10 daily sessions. During the tDCS stimulation a constant current of 2 mA was delivered for 30 minutes. Clinical evaluations were performed at baseline, day 11, day 30 and at day 90. The PSP-Rating score (total and sections I & III) improved significantly on day 11 compared to baseline and similarly on day 30. A positive effect was also seen on action tremor. In addition to the global mental status improvement, patients showed increases in neuropsychological performance in the domains of visuo-motor co-ordination and processing speed, auditory-verbal learning, episodic memory,phonological and semantic fluency (access and retrieval from lexical memory, selective inhibition and lexical access speed). Our results suggest that tDCS has a beneficial effect on Progressive Supranuclear Palsy patients' bulbar and motor symptoms, cognitive dysfunction, as well as daily activities, which lasts beyond the duration of the treatment.