Changes in cerebral glucose metabolism after 3 weeks of noninvasive electrical stimulation of mild cognitive impairment patients

In this study we observed the longitudinal effects of tDCS in MCI patients and measured metabolic activity in pre-treatment and post-treatment conditions. In the active tDCS group, brain metabolism was significantly increased after 3 weeks (total nine sessions) of tDCS treatment, and the post-treatment brain metabolism was significantly higher in the active tDCS group than in the sham group. Previous studies have shown that even a single session could enhance the cognitive performance in dementia patients [16, 17, 20]. Our findings suggest that regular and frequent administration of tDCS in MCI patients can modulate the metabolism of certain brain regions as well as enhance neuropsychological performance. Improvement of cognitive function after tDCS might not be a transient effect, because regular stimulation (i.e., daily sessions for 5 days) improved visual recognition memory for 4 weeks after stimulation [21].

We found that the cerebral metabolic activity of MCI patients significantly increased after tDCS administration, especially in the active treatment group compared with the sham control group. A previous study showed that MCI and dementia patients have higher 2-(1-(6-((2-fluoroethyl) (methyl) amino)-2-naphthyl)ethylidene) alononitrile (FDDNP) binding and lower 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in the temporal, parietal, posterior cingulate, and frontal regions [47]. Two proteins, beta-amyloid and tau, are abnormally accumulated in these regions in dementia patients [48], and neurofibrillary tangles have also been detected in the medial temporal and hippocampal regions in MCI patients [49]. This neuropathological finding might correlate with metabolic activity of the brain, because the patients with dementia showed significantly lower glucose metabolism in similar regions, such as the parietal, temporal, frontal, and posterior cingulate cortices [50]. In this study, we found increased FDG uptake in multiple brain regions, including the anterior and posterior insular, hippocampal, and parahippocampal regions, especially in the active tDCS administration group. Previous studies showed that tDCS increased the brain metabolism as compared with sham stimulation [51, 52]. Therefore, we speculate that increased brain metabolism and cognitive improvements in MCI patients were due to a noninvasive neuromodulatory effect rather than a placebo effect.

Furthermore, we found that participants’ reports of their memory ability, which was measured by the MMQ-A and MMQ-C subscales, were significantly improved only in the real tDCS group. The MMQ-A subscale consisted of 20 items and assessed memory lapses in everyday activities such as names of people and locations of items [53]. A higher score on the MMQ-A subscale indicates individuals who are less likely to experience memory problems in their daily life and are satisfied with their own memory function. The MMQ-C subscale also measures the subjective satisfaction of patients’ memory abilities and determines whether subjects experience anxiety regarding their memory problems. Although participants in our study did not know whether they were assigned to the real or sham tDCS group, both the MMQ-A and MMQ-C scores were significantly higher only in the real tDCS group after 3 weeks of stimulation. This result suggests that regular use of tDCS might improve the overall contentment or satisfaction of patients with their memory ability as well as enhance their metabolic activity.

Previous studies have noted that MCI patients have a risk of progression to dementia, and the baseline memory performance significantly predicted the conversion to dementia [1]. Although various clinical interventions have examined symptomatic drug treatment for MCI patients, there is no significant evidence that anti-dementia drugs lower the progression rate from MCI to dementia during 1–3 years of treatment [4]. Regarding the therapeutic effect of tDCS on various neuropsychiatric diseases, such as depression, schizophrenia, and dementia [16], our findings suggest that regular and relatively long-term administration of tDCS might enhance cognitive performance in MCI patients.

One limitation of our study is the short observation period compared with conventional pharmacological interventions, which have a 6-month to 3-year treatment period [4]. Although the effect of tDCS is known to last for weeks after administration [21], a longer observation period might be needed to confirm whether the use of tDCS slows or stops the conversion of MCI to dementia. Furthermore, a recent study used more frequent tDCS administration consisting of daily sessions for 5 days during 1 week [21]. Although most studies have used a single session per subject [17, 20], the current tDCS protocol for MCI and dementia has not been optimized. Other studies have shown improvement in memory function of dementia patients after tDCS treatment [16], and the standardization of the duration, electrode size, and current strength of tDCS administration on MCI and dementia patients is needed. It should also be mentioned that the PET images and the test scores were the results of the combined effect of the long-term (3 weeks) and the short-term tDCS treatments because the last PET imaging and the neuropsychological testing were performed right after the last tDCS treatment. The experimental design was not optimal to exclude the acute effect of stimulation but we believe that the acute effect was still part of the long-term effect. Further long-term and large-scale research is warranted to confirm the effect of tDCS on MCI.