tDCS application to the DLPFC is associated with the improvements of executive function, memory enhancement, language, processing speed, global cognitive symptoms and apathy over time after treatment. DLB is the second most common form of degenerative dementia. There is no FDA-approved medications that can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation(LTP), and influence memory and learning. tDCS has been proposed to affect long-term synaptic plasticity through LTP and long-term depression, thereby improving cognitive ability. So far, only two studies have evaluated the effect of tDCS in DLB. In this pilot study, we investigate the effect of tDCS on left DLPFC in DLB.

Fourteen DLB aged 55-90 years (mean age 76.4, with 4 males and 10 females) were included in a double-blind, randomized, sham-controlled cross over design study. DLB diagnostics is according to DSM-5 criteria. CDR ratings for DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process consists of daily sessions of active tDCS (or sham) for 10 consecutive days. The anodal electrode was placed over the left DLPFC and the cathodal electrode was placed over the right supraorbital area, with a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in a session. Before and after these treatment sessions, all subjects received a series of neuropsychological tests, including CDR, MMSE, CASI, NPI and WCST. Chi-square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess differences in participant demographic characteristics and to compare differences among groups.

The active tDCS group showed significant improvements on the three items of CASI, ‘language ability’, ‘concentration and calculation’, ‘categorical verbal fluency’, after active stimulations. There is no improvement in MMSE, CASI, NPI and WCST scores in the sham groups.

These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, may have some cognitive benefits in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Key words: Transcranial Direct Current Stimulation, Dementia with Lewy Bodies, cognitive function, Wisconsin Card Sorting Test, left DLPFC

Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. In pathology, the amyloid deposits in AD disrupts the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. An increasing number of studies have been concluded a positive therapeutic effect on cognition in AD. In brain stimulation, dorsolateral prefrontal cortex (DLPFC) was associated with improvements in memory enhancement, language, processing speed, global cognitive symptoms, and apathy over a period of treatment. Theoretically, the aftereffect of tDCS would need to be re-stimulated by tDCS to maintain its delayed plastic response benefits. In this pilot study, we investigate the maintenance effects of continuing tDCS at three different times, weekly, every two weeks, and every four weeks, for 12 weeks.

Twenty-eight AD participants aged 55-90 years were enrolled (mean age 72.7, 77.3, and 76.2 in the three groups - maintained weekly (7 cases), biweekly (9 cases) and every 4 weeks (12 cases)). The anodal electrode was placed over the left dorsal lateral prefrontal cortex and the cathodal electrode was placed over the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at (1) baseline, (2) post-10sessions of tDCS (in 2weeks), and (3) post-maintenance phase (total of 12 weeks). Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess differences in participant demographic characteristics and to compare differences in test scores between groups.

After 10 sessions of tDCS stimulations, the total CASI scores in the 1-week group improved significantly from baseline to 2 weeks. However, there are no significant difference in MMSE, CASI or WCST between baseline and after maintain phase stimulations in each group.

Although tDCS has a positive effect in AD, it is recommended to prolong the number of tDCS stimulations, such as 20 sessions in 4 weeks.

To explore and develop effective treatments is crucial for patients with Alzheimer’s dementia (AD). In pathology, the amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Although an increasing number of studies have been concluded a positive therapeutic effect on cognition in AD, tDCS studies to date are limited on exploring the duration of its efficacy. In this pilot study, we investigate the effects of tDCS in AD and verify its extending beneficial effects for 3 months follow-up period after the end of stimulation.

34 AD participants aged 55-90 years (mean age 75.9 (66-86)) were included in a double-blind, randomized, sham-controlled crossover study. All participants were randomly assigned to receive 10 consecutive daily sessions of active tDCS (or sham) and switched groups 3 months later. The anodal electrode was on the left dorsal lateral prefrontal cortex and the cathodal electrode was on the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at baseline and in 2 weeks, 4 weeks, and 12 weeks post-tDCS (or sham) 10 sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences of test scores between groups.

The active tDCS group showed significant improvements on CASI total scores from baseline to 2-weeks, 1-month and 3-months after active stimulations, though the improvement declined over time. There are also different presentations in total correct items, conceptual level responses, failure to maintain sets of WCST between active tDCS and sham groups. There is no difference in MMSE, CASI and WCST scores in the sham groups.

These results suggest a long term-beneficial effects of tDCS in AD.

Dementia with Lewy Bodies (DLB), this second most common form of degenerative dementia, presents more functional disability, more potentially fatal complication, more impaired quality of life than Alzheimer’s dementia. There is no FDA-proved medication can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation, and influence memory and learning. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. So far, only two researches assess the effect of tDCS in DLB. In this pilot study, we investigate the effects of tDCS in DLB.

Using a double-blind, randomized, sham- controlled and crossover trial design, 11 DLB aged 55-90 years (mean age 77.8) were included in the study. DLB diagnostics is according to DSM-5 criteria. The CDR ratings of DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process includes consecutive daily sessions of active tDCS (or sham) for 10 days. The anodal electrode was over the left dorsal lateral prefrontal cortex (DLPFC) and the cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI, NPI and WCST, before and after these treatment sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences among groups.

On CASI, MMSE, NPI and WCST, there were no statistically significant differences between pre- and post the 10-session course for the active and the sham groups. No side effects reported during or immediately after active tDCS stimulation.

These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, do not improve cognition, behavioral and psychological symptoms in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Identifying effective treatments is a critical issue for Alzheimer’s dementia (AD). The pathological amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Brain stimulation in dementia research, especially with relatively safe tDCS, has been taken seriously recently. In theory, tDCS affects long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Recently, an increasing number of studies have been conducted to evaluate the efficacy of tDCS in AD and concluded a positive therapeutic effect. Currently, there are no studies of tDCS for AD in Taiwan. In this study, we investigate the effects of tDCS in AD.

Using a double-blind, randomized and sham- controlled trial design, Sixteen AD aged 55-90 years (8 active, mean age 73.88 and 8 sham, mean age 74.75) were included in the study. AD diagnostics is according to DSM-5 criteria. The CDR ratings of AD participants ranged from 0.5 to 2. All subjects completed ten consecutive daily sessions in which they received either an active or a sham tDCS over the left dorsal lateral prefrontal cortex (anodal) and a cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 35 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI and WCST, before and after these treatment sessions on the first day and 4 weeks later. Chi- square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess the differences in participant demographic characteristics and to compare the differences among groups.

The active group showed significant improvement in total correct item, Conceptual level Responses (reflecting insight into the correct sorting principles), Categories Completed (reflecting overall success), and Trials to complete first categories (reflecting initial conceptual ability) of WCST 4 weeks later after the final stimulation. There were no statistically significant differences between before and after the 10-session course for the sham group.

tDCS stimulation improves cognitive operation and Conceptual Ability of AD.

The aim of this study was to examine and test the sensitivity, specificity, and threshold scores of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) and determine those that best correspond to a clinical diagnosis of dementia with Lewy bodies (DLB).

Sixty-seven Alzheimer's disease (AD), 36 DLB, and 62 healthy participants without dementia (NC), aged 60 to 90, were enrolled. All three groups took the MoCA and MMSE tests at the same time. The Cochran–Mantel–Haenszel tests and receiver operating characteristics curve analysis were used to compare the different neuropsychological test results among the groups.

The cut-off point of the MoCA for AD was 21/22 with a sensitivity of 95.5% and a specificity of 82.3% (area under the curve (AUC): 0.945), and the cut-off point for DLB was 22/23 with a sensitivity of 91.7% and a specificity of 80.6% (AUC: 0.932). For the MMSE, the cut-off points for AD and for DLB from NC were all 24/25, with a sensitivity of 88.1% and a specificity of 85.5% for AD (AUC: 0.92), and a sensitivity of 77.8% and a specificity of 85.5% for DLB (AUC: 0.895). After controlling sex, age, and education, AD and DLB had lower scores in all MoCA subscales than the NC group (p < 0.05), except for the orientation and naming in DLB. In addition, AD had a lower score in the MoCA orientation (p = 0.03) and short-term memory (p = 0.02) than did DLB.

The MoCA is a more sensitive instrument than the MMSE to screen AD or DLB patients from non-dementia cases.