Main objective and evaluation criteria:
To evaluate the potential therapeutic efficacy of repetitive tDCS during 10 days on language/semantic impairment in SD via a double-blind sham-controlled study design. The evaluation criteria will be a significant improvement of language/semantic performances two weeks after tDCS as compared to base-line (before tDCS), contrasting subgroups receiving left-excitatory or right-inhibitory tDCS vs. sham tDCS
Secondary objectives and evaluation criteria:
1. Assess the time course of potential language/semantic improvement through the application of four follow-up time-points: base-line (max one week before tDCS), three days, two weeks and four months after tDCS. The evaluation criteria will be significant improvement/modulation of language/semantic performances, comparing performances at the four time-points.
2. Assess brain markers which could reflect stimulation-induced neuroplasticity. Evaluation criteria will be significant modulation of cortical metabolism (FDG-PET) and functional connectivity (fMRI resting-state) comparing base-line and the 'two-week' time-point.
3. Compare left-excitatory and right-inhibitory tDCS to reveal the most efficient stimulation modality. Evaluation criteria will be a detection of a potential outcome difference between left-excitatory and right-inhibitory tDCS on the performance within the different language/semantic tasks.
4. Improve the understanding of the semantic roles of the left and right temporal pole, and their potential anatomical connectivity, by comparing left and right temporal pole stimulation and using MRI-based fiber tracking. 4) Improve the understanding of the semantic roles of the left and right temporal pole, and their potential anatomical connectivity, by comparing left and right temporal pole stimulation and using MRI-based fiber tracking.
Experimental design :
10 days of stimulation (20min, 2mA). Four language/semantic evaluations: base-line; 3 days; 2 weeks; 4 months post-tDCS. Two MRI/PET acquisitions: pre-stimulation (base-line); 2 weeks post-tDCS
Population :
Patients with semantic dementia (SD). Healthy controls for normative measures (no tDCS for controls)
Testing treatment :
tDCS (specific device) : NE STARSTIM-ENOBIO 8 channels.
Practical procedure :
The duration of the study will be 41 months; 36 months being dedicated to patient inclusion. Participation duration of a patient will be of 4 months and 1 week to 4 months and 3 weeks maximum. First, patients will undergo a series of standardized neuropsychological and language tests that are included in routine care and inclusion criteria will be checked. After inclusion, the base-line visit will comprehend 1) MRI/PET in the Nuclear Medicine Service (CHU Pitié Salpêtrière), and 2) language/semantic tasks at the Department of Neurology (CHU Pitié Salpêtrière). Subsequently the ten stimulation sessions will be scheduled. They will take place in the Institute of Memory and Alzheimer's disease (Department of Neurology, CHU Pitié Salpêtrière) during two consecutive weeks (20 minutes of tDCS). The tDCS sessions will be followed by three time-point visits: 3 days (time-point 2) and two weeks (time-point 3) after the last stimulation session patients will undergo the language/semantic tasks. At time point 3 the second MRI/PET acquisition will take place. Finally, the visit of time-point 4 will be at four months after the last tDCS session, dedicated to a last application of language/semantic tasks.
Selected number of subjects:
80 SD patients selected in order to have 60 randomized into three arms (20 patients/arm).Two arms receiving active tDCS versus one receiving sham tDCS.
20 healthy volunteers will be included (participants will provide normative language/semantic scores and MRI/PET measures; they will not undergotDCS).
Number of centers: 3 centers in France (Paris)
Research duration:
Inclusion period: 36 months Participation period (Selection/inclusion, tDCS sessions and evaluation at 4 time-points): 4 months and 1 week to 4 months and 3 weeks Total duration: 41 months
Funding source: AP-HP (Assistance Publique des Hôpitaux de Paris).
