Feasibility and Benefits of Intermittent Multiple tDCS Courses With Concomitant Language Training in Semantic Dementia: A Case Report

Dear Editor,

Semantic variant primary progressive aphasia (svPPA) is a language variant of frontotemporal dementia (FTD). Treatment with cholinesterase inhibitors has been used in a few clinical trials with no definite benefit. Another treatment modality is language intervention, e.g., utilizing residual semantic knowledge to provide personalized language training. ¹ The role of noninvasive brain stimulation, which includes transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation, has been studied. However, there is no standardized treatment. The utility of tDCS has been investigated as monotherapy as well as an augmentation strategy to language training. However, the long-term effect is unclear. ¹ We report the effect of tDCS combined with language training on language and behavioral outcomes in a patient with svPPA who underwent multiple phases of treatment over two years.

A 61-year-old lady diagnosed with svPPA as per international consensus criteria, ² with 2.5 years of symptoms, was recruited for the intervention after taking written informed consent. Later, consent was also taken for publication of the case report. Addenbrooke’s Cognitive Examination III, Kannada (ACE-IIIK), Frontal Behavioural Inventory (FBI), and Western Aphasia Battery, Kannada (WAB-K) were administered at baseline and follow-up. tDCS was administered in three phases. Anodal left dorsolateral prefrontal cortex (DLPFC) stimulation of 2 mA with 35 cm² electrodes, with cathode over the right supraorbital region, was chosen as the montage. In phase I (P1), two 20-min tDCS sessions/day separated by 3 h were administered for 10 days. The speech–language pathologist provided offline speech and language intervention (SLIn) for 10 days. (As per Schuell’s stimulation approach, thematic language stimulation and cognitive stimulation for rehabilitation ³ were followed.) Specific goals were set based on baseline assessment. The speech therapy sessions were carried out every day (30 min duration) in the caregiver’s presence, followed by partner or caregiver training ³ (20 min duration). Caregiver training ensured the generalization of goals to the home environment.

In phase II (P2), after two months, tDCS was provided one session/day (30–45 min), along with concomitant SLIn only for the last five sessions. The sessions were carried out by the caregiver and monitored by speech–language pathologist.

In phase III (P3), after one year, 10 sessions of tDCS were given with the same montage as above but as two sessions/day of 20 min each, separated by 20 min. The stabilization of pharmacotherapy was ensured before each phase.

Overall cognition and behavior improved after P1 and P2 (FBI score change: P1: -9, P2: -3), but the scores returned to near baseline within two months. Improvement in language was better with concomitant SLIn (aphasia quotient [AQ]: pre-P1, post-P1: 49.8, 55.0; pre-P2, post-P2: 52.4, 69.0). P3 did not offer additional gains. There were no adverse effects, as ascertained by a structured questionnaire. ⁴

Most of the studies on primary progressive aphasia have involved the nonfluent variant or the logopenic variant. A proof-of-concept study had evaluated semantic accuracy in 12 subjects with svPPA in a randomized, double-blind, crossover study of one session each of three different stimulation categories—anodal stimulation to left temporal pole, cathodal stimulation of right temporal pole, and sham stimulation. It reported improved semantic accuracy with left anodal stimulation and improved processing speed with right cathodal stimulation. ¹ Intermittent booster tDCS has been used in cases of substance dependence and schizophrenia, where it was given while there was a relapse of target symptoms.^5,6 In our patient, language functions improved with P1, which sustained until P2. There is no approved protocol for tDCS in svPPA. There is variability in the number of sessions in the previously published studies. Hence, further phases were initiated based on feasibility, at the caregivers’ request, as they appreciated the improvement in her everyday communication after P1. tDCS concomitant with language training offered an additional improvement as evidenced by the scores on WAB-K. However, her language functions could not be reassessed after P3, as she was not cooperative. During P1, her behavioral symptoms, especially stereotypy, perseveration, and anxiety, responded well. However, they reappeared in 50 days. Notably, there was no additional improvement with P3.

In this patient, we used three different stimulation protocols. We chose the stimulation parameters considering the target symptoms. In P1 and P2, the target was language function. In a case report, tDCS over the same montages has been beneficial in apathy in behavioral variant of FTD. ⁷ As our patient’s behavioral symptoms showed improvement in P1 and P2, we proceeded with P3 targeting the symptoms of stereotypy, insistence on sameness, and perseveration. The same parameters have been effective in obsessive compulsive disorder and therefore were chosen for this patient. ⁸ The neuroanatomical correlates of stereotypy in FTD are unclear, but the frontostriatal circuits have been implicated. ⁹ The plateauing of the response could have contribution from the longer interphase interval and the natural course of the illness. svPPA is a degenerative disorder with cognitive and behavioral symptoms, which hinder the determination of a “Goldilocks” montage. We chose the left DLPFC as the target for anodal stimulation. The memory, unification, and control (MUC) model implicates the temporo-parietal as well as the frontal regions, including DLPFC, in language. ¹⁰ DLPFC is also implicated in behavioral symptoms, namely apathy and stereotypy.^9,11 DLPFC is also a superficially located area of the brain that can be easily targeted by conventional tDCS.

tDCS, with its advantage of being domiciliary friendly, ¹² can be a feasible treatment option for degenerative disorders with no approved treatment. Clinical trials evaluating the long-term effects are implicated. Protocols for tele-assisted domiciliary tDCS are under development. Concomitant tDCS and SLIn can be done through tele- assisted modality. There is a potential for enhanced utilization of long-term tDCS for svPPA in the future.