A Scoping Review Of Neuromodulation Techniques in Neurodegenerative Diseases: A Useful Tool For Clinical Practice? Part 4

3.3.2. Transcranial Direct Current Stimulation-tDCS

Various studies investigated the effects of tDCS on cognition in PD patients. It was generally observed that anodal stimulation of the dorsolateral prefrontal cortex (DLPFC) resulted in significant improvements in WM [99], phonemic verbal fluency [100], and executive functions [101]. 

Parkinson's disease is a neurological disease whose main symptoms include tremors, rigidity, and movement disorders. However, studies have shown that Parkinson's patients have worse memory than healthy people. However, we need to look at this phenomenon positively and help patients improve their memory as much as possible.

First, we need to know that Parkinson's patients suffer from impaired memory because it affects some parts of their brains. These parts include the cerebral cortex and hippocampus, which are important for learning, storing, and retrieving information. However, this does not mean that patients can never recover their memory ability.

Second, some many methods and strategies can help Parkinson's patients improve their memory. For example, they can use memory enhancement techniques such as association, imagination, and imagery to help them remember information. Objects and visual cues can also be used to help them recall information. In addition, performing simple daily life exercises, such as crossword puzzles, Sudoku, and video games, can also help improve their cognitive function and memory.

Finally, we also need to maintain an optimistic attitude and help Parkinson's patients overcome any negative emotions that may affect their memory. Through regular physical exercise, good sleep habits, a balanced diet, and social interaction with friends and family, we can help patients alleviate the effects of the disease and improve their quality of life.

In short, although Parkinson's patients may face medical challenges, they should always be encouraged to actively deal with these challenges, give them the motivation to move forward, and continuously improve their self-confidence and memory levels. It can be seen that we need to improve memory, and Cistanche can significantly improve memory because Cistanche is a traditional Chinese medicine with many unique effects, one of which is to improve memory. The efficacy of Cistanche comes from its various active ingredients, including tannic acid, polysaccharides, flavonoid glycosides, etc., which can promote brain health in many ways.

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In this latter study, changes in executive functions were measured by the Trail Making Test, and it was also shown that benefits deriving from tDCS stimulation lasted after the one-month follow-up. 

More recently, in agreement with these results in a double-blind, randomized, and sham-controlled study, a 20 min at two mA stimulation of the DLPFC was given to twenty participants who were tested before and after stimulation with the Trail Making Test (TMT), verbal fluency test, Stroop test, timed up-and-go test and video gait analysis. Improvements due to stimulations were observed in the verbal fluency test and the Stroop test [102]. 

A promising approach considers the possibility of integrating cognitive training and brain stimulation. 

To this aim, in a recent study by Lawrence et al., the authors examined the different effects on cognitive function and functional outcomes in PD patients with MCI, of standard cognitive training (1), tailored cognitive training (2), tDCS stimulation (3), standard cognitive training in association with tDCS (4), or tailored cognitive training in association with tDCS (5). In all cases, tDCS consisted of anodal stimulation of the left DLPFC. 

All interventions lasted four weeks, with cognitive and functional outcomes measured at baseline, post-intervention, and follow-up. Results showed that when compared to the control group, all of the five intervention groups demonstrated variable statistically significant improvement across executive function, attention/working memory, memory, language, activities of daily living (ADL), and QoL. 

Most importantly, it was shown that combining tDCS with tailored/standard cognitive training provided greater therapeutic effects [103]. Similarly, in a study by Manenti et al., 22 patients with PD underwent a two-week treatment involving the daily application of active tDCS plus computerized cognitive training (CCT) or sham tDCS plus CCT. 

Each patient was evaluated at baseline, after treatment, and at the three-month follow-up. The results pointed out that, while an improvement in general cognitive performance was observed in both groups at posttreatment and follow-up, greater and significant changes from the baseline of phonemic verbal fluency were exclusively present in the active tDCS group [104]. 

Finally, another study by the same group of researchers [105] investigated the effects of anodal transcranial direct current stimulation applied over the DLPFC, combined this time with physical therapy in 20 PD patients. 

These were assigned to one of two study groups-group 1, anodal tDCS plus physical therapy (n = 10); or group 2, placebo tDCS plus physical therapy (n = 10). The treatment, lasting two weeks, consisted of daily direct current stimulation application for 25 min during physical therapy. 

The long-term effects of the treatment were evaluated on clinical, neuropsychological, and motor task performance at the three-month follow-up. The authors pointed out an improvement in motor abilities and a reduction of depressive symptoms in both groups after the end of treatment and at the three-month follow-up. 

However, the Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. 

Taken together, all of these studies showed that tDCS could produce a series of significant improvements in motor and non-motor symptoms in PD and that this may be a relevant tool to improve cognitive abilities in PD, providing a novel therapeutic strategy for patients with mild cognitive impairment. Table 2 contains the main information about the studies reviewed.

4. Conclusions

Neurodegenerative diseases are heterogeneous in their clinical profiles and underlying pathophysiology. In most cases, they share the presence of significant cognitive impairment, depending on the diseases themselves and their clinical stage. 

Due to the absence of effective pharmacological treatments for their most prominent cognitive symptoms, researchers and clinicians are in urgent need of valid tools to contrast patients' decay. 

Non-invasive brain stimulation techniques such as TMS and tDCS are safe and effective methods for improving cognitive and affective functions in neuropsychiatric disorders such as depression, anxiety, and PTSD symptoms. 

As reviewed in the present paper, neuromodulation techniques may represent a promising tool for treating the cognitive symptoms of neurodegenerative conditions in the elderly, as the preliminary evidence provided by the pilot studies published so far is encouraging. 

However, as current research in the field has not reached a mature level already and thus its results should be considered necessarily as preliminary, our review points out the need for further and more robust studies including larger samples of patients and a more efficient integration of neuromodulation techniques and cognitive tools. 

A better definition of treatments' targets and more coherence in experimental design and clinical outcomes will generate a clearer picture of neuromodulation techniques' efficacy in these neurodegenerative conditions. 

To conclude, at this point, given the absence of large and robust studies able to provide strong evidence in favor of the use of these techniques with these clinical targets, one cannot draw any definitive conclusion about their efficacy although preliminary evidence is encouraging (please refer to Tables 1–3, which show a significant improvement of patients in 34 out of the 46 studies considered). 

By referring to widely accepted classifications of efficacy (e.g., grade practice recommendations), at this point, the level of recommendation considers these techniques a viable therapeutic option, meaning that the qualifying evidence can be classified as levels II, III, or IV with findings not always consistent across all studies. 

However, in our view, larger and more robust studies would help to overcome some of the limitations that small-scale studies currently present. 

In doing so, more evidence-based clinical reasoning will permit serious consideration of the possible integration of innovative neuromodulation techniques with more traditional interventions targeting neurodegenerative patients with cognitive rehabilitative purposes in mind.

Author Contributions: Conceptualisation, F.M., S.L., and M.C.; methodology, F.M., S.L., and M.C.; investigation, F.M., S.L., and M.C.; resources, F.M., S.L., and M.C.; data curation, F.M., S.L., and M.C.; writing-original draft preparation, F.M., S.L., and M.C.; writing-review and editing, F.M., S.L. and M.C.; supervision, M.C.; funding acquisition, M.C. All authors have read and agreed to the published version of the manuscript.

Funding: This research received no external funding.

Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.

Data Availability Statement: No new data were created or analyzed in this study. Data sharing does not apply to this article.

Conflicts of Interest: The authors declare no conflict of interest.

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