Is transcranial direct current stimulation really beneficial for frontotemporal dementia?

We were interested to read the article by Tippett et al. on the therapeutic effect of home transcranial direct current stimulation (tDCS) combined with computerized cognitive training (CCT) in a single patient with probable frontotemporal dementia (FTD). ¹ At follow-up after 10 weeks of treatment, the patient improved by 3 points on the Mini-Mental State Examination (MMSE) (23 to 26) and showed improvements in immediate recall of single words and word pairs, total number of correct words in sentence repetition, delayed recall, semantic processing, and sentence-level comprehension. ¹ Family members reported improvements in expressive language, communication and interaction with others, as well as increased attention to grooming and hairstyle. ¹ The study concluded that tDCS in combination with CCT over a 10-week period can slow and improve the deterioration of cognitive/language performance and daily functioning in FTD. ¹ The study is impressive, but several points need to be discussed.

The first point is that the MMSE was used to assess changes in the cognitive functions of the index patient. Disadvantages of the MMSE are that the method is highly susceptible to interference, that the method can only roughly capture cognitive deficits (eg, the MMSE can often lead to a false negative result in patients with a high level of education, while there is a risk of a false positive result in patients with a low level of education) and that the MMSE cannot be used to differentiate between different cognitive abilities. ² Therefore, it is often necessary to use or combine more comprehensive tests such as the Memory Impairment Screen (MIS), Mental Status Questionnaire (MSQ), Functional Activities Questionnaire (FAQ), the St. Louis University Mental Status Examination (SLUMS), or the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) to identify the specific cognitive deficits of a particular patient. It should be explained why the index patient improved on the MMSE but not on the MoCA test. Could this be due to the fact that the 2 tests partially capture different aspects of cognitive functioning?

The second point is that the patient received 2 therapies during the observation period of 10 weeks, ¹ which makes it difficult to assess whether 1 or the other or both were beneficial and responsible for the 3-point increase in the MMSE. As long as a patient receives 2 therapies simultaneously and experiences a positive effect, it is not possible to decide which of the 2 therapies was actually effective.

The third point is that the design (single case) is unsuitable for assessing whether a therapy is generally effective or not. In order to adequately assess whether a particular therapy is truly beneficial, ineffective or harmful, an appropriate design (eg, randomised controlled trial (RCT), open-label or double-blind, placebo-controlled, cross-over or parallel trial (OLPCT, DBPCPT, DDBPCCT)) must be used and a sufficient number of patients must be prospectively studied.

The fourth point is that FTD is often associated with familial amyotrophic lateral sclerosis (fALS) due to mutations in C9orf72. ³ Therefore, we should know whether the index patient or any of her first-degree relatives had symptoms or signs of motor neuron disease.

The fifth point is that no electroencephalography (EEG) results were provided. ¹ Since FTD may be associated with epilepsy, ⁴ we should know whether the index patient had a history of seizures or whether the EEG recording showed paroxysmal activity.

In summary, the reported data have some limitations that put the given recommendations into perspective. Addressing these limitations could strengthen the conclusions and increase the value of the guidelines.