Efficacy of Transcranial Direct Current Stimulation Combined with Cognitive Training in the Treatment of Apathy in Patients with Alzheimer's Disease: Study Protocol for a Randomized Trial (original) (raw)
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Brain Stimulation, 2014
Background: Apathy is the most common neuropsychiatric symptom in Alzheimer's disease (AD) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions. To date no effective treatment for apathy has been demonstrated. Objective: We aimed to investigate the effects and safety of repetitive transcranial direct current stimulation (tDCS) on apathy in moderate AD patients. Methods: Forty patients were randomized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex (DLPFC). Patients received six sessions of intervention during 2 weeks and were evaluated at baseline, at week 1 and 2, and after 1 week without intervention. Clinical raters, patients, and caregivers were blinded. The primary outcome was apathy. Global cognition and neuropsychiatric symptoms were examined as secondary outcomes. Results: The mean MMSE score at baseline was 15.2 AE 2.9 and the mean Apathy Scale score was 27.7 AE 6.7. Changes on apathy scores over time were not different between active and sham tDCS (P ¼ 0.552 for repeated measures). Further analyses confirm that changes from baseline did not differ between groups after the sixth session (active tDCS À1.95 (95%CI À3.49, À0.41); sham-tDCS À2.05 (95% CI À3.68, À0.42); P ¼ 0.989]. Similarly, tDCS had no effect on secondary outcomes (P > 0.40). tDCS was well tolerated and not associated with significant adverse effects. Conclusion: In this adequately powered study for minimal clinically significant difference, our findings show that using the parameters we chose for this study, repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD.
JMIR Research Protocols, 2021
Background Many clinical trials investigating treatment efficacy require an interim analysis. Recently we have been running a large, multisite, randomized, placebo-controlled, double-blind clinical trial investigating the effect of repetitive transcranial magnetic stimulation (rTMS) treatment for improving or stabilizing the cognition of patients diagnosed with Alzheimer disease. Objective The objectives of this paper are to report on recruitment, adherence, and adverse events (AEs) to date, and to describe in detail the protocol for interim analysis of the clinical trial data. The protocol will investigate whether the trial is likely to reach its objectives if continued to the planned maximum sample size. Methods The specific requirements of the analytic protocol are to (1) ensure the double-blind nature of the data while doing the analysis, (2) estimate the predictive probabilities of success (PPoSs), (3) estimate the numbers needed to treat, (4) re-estimate the initial required s...
Journal of Neural Transmission, 2012
Cortical excitability can be modulated using repetitive transcranial magnetic stimulation (rTMS). Previously, we showed that rTMS combined with cognitive training (rTMS-COG) has positive results in Alzheimer’s disease (AD). The goal of this randomized double-blind, controlled study was to examine the safety and efficacy of rTMS-COG in AD. Fifteen AD patients received 1-h daily rTMS-COG or sham treatment (seven treated, eight placebo), five sessions/week for 6 weeks, followed by biweekly sessions for 3 months. The primary outcome was improvement of the cognitive score. The secondary outcome included improvement in the Clinical Global Impression of Change (CGIC) and Neuropsychiatric Inventory (NPI). There was an improvement in the average ADAS-cog score of 3.76 points after 6 weeks in the treatment group compared to 0.47 in the placebo group and 3.52 points after 4.5 months of treatment, compared to worsening of 0.38 in the placebo (P = 0.04 and P = 0.05, respectively). There was also...
2017
Objectives: Dementia of Alzheimer Type (DAT) is associated with progressive cognitive impairments. Such a clinically significant condition is known to affect approximately 9.5% of people over 70 years of age. However, it is accepted as a more challengeable medical entity because of its increasing atypical presentation, rarity of efficient treatments, and diagnostic and prevention challenges. Materials & Methods: we present a case who referred with 5 months history of cognitive decline following Medial Temporal Lobe (MTL) atrophy upon neuroimaging. Following cognitive and neurophysiological assessments, she underwent 21 consecutive sessions of transcranial Direct Current Stimulation (tDCS) 3 times per week. Concurrently, a media-rich computer platform was administered for cognitive and behavioral remediation. Results: Based on the evidence regarding the use of tDCS in dementia, we aimed at stabilizing the cognitive profile and halting or slowing down the process of progressive cognitive decline in the present case. The outcome of our neuromodulatory intervention using tDCS supported the beneficial impact of such an approach in not only stabilizing but also ameliorating cognitive functions. This is especially important when rapid progression of cognitive symptoms in DAT is of concern. Conclusion: The promising clinical course of this specific case supports the possible beneficial effects of tDCS in halting the progression of symptoms in DAT. Sham-controlled clinical trials would get momentum to highlight clinical impact of such an intervention in DAT.
Neuropsychological Rehabilitation, 2014
In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60 years, mild AD) underwent two cycles of treatments, separated by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20 min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient's global cognitive functioning lasting approximately 3 months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient.
Journal of Advanced Medical Sciences and Applied Technologies
Dementia of Alzheimer Type (DAT) is associated with progressive cognitive impairments. Such a clinically significant condition is known to affect approximately 9.5% of people over 70 years of age. However, it is accepted as a more challengeable medical entity because of its increasing atypical presentation, rarity of efficient treatments, and diagnostic and prevention challenges. Materials & Methods: we present a case who referred with 5 months history of cognitive decline following Medial Temporal Lobe (MTL) atrophy upon neuroimaging. Following cognitive and neurophysiological assessments, she underwent 21 consecutive sessions of transcranial Direct Current Stimulation (tDCS) 3 times per week. Concurrently, a media-rich computer platform was administered for cognitive and behavioral remediation. Results: Based on the evidence regarding the use of tDCS in dementia, we aimed at stabilizing the cognitive profile and halting or slowing down the process of progressive cognitive decline in the present case. The outcome of our neuromodulatory intervention using tDCS supported the beneficial impact of such an approach in not only stabilizing but also ameliorating cognitive functions. This is especially important when rapid progression of cognitive symptoms in DAT is of concern. Conclusion: The promising clinical course of this specific case supports the possible beneficial effects of tDCS in halting the progression of symptoms in DAT. Sham-controlled clinical trials would get momentum to highlight clinical impact of such an intervention in DAT.
Clinical Psychopharmacology and Neuroscience
Transcranial direct current stimulation (tDCS) is a form of novel brain stimulating method that has attracted interest owing to its relative inexpensiveness and ease of administration. It has been evaluated in many studies for its effectiveness in improving cognitive symptoms in Alzheimer's disease (AD). However, our understanding regarding its efficacy and the most effective way of administering tDCS (in terms of lead placement to achieve response and prevent harmful consequences) is still evolving. The current meta-analysis was conducted to resolve the above issues. A search using appropriate keywords and medical subject headings was conducted on PubMed, Scopus and DOAJ database. Studies were analysed on pre-defined inclusion and exclusion criteria. Finally 11 studies were included for quantitative analysis from 1,021 obtained from initial search. All the studies included were methodologically of high quality, though an asymmetrical funnel plot raised the possibility of publication bias. tDCS was found to significantly improve the scores on cognition as compared to sham. Anodal tDCS was found to be significantly beneficial in this regards, whereas cathodal and dual stimulation were not. There were no significant difference in the number of drop-outs and adverse reaction in tDCS and sham group. The quality of evidence that we have reviewed in this study is robust. tDCS, particularly anodal tDCS is an effective treatment modality in AD. It is well tolerated in patients with AD. However, further studies are warranted to probe the role of tDCS in other domains of AD.
BMC research notes, 2018
Alzheimer's disease is a major health problem in our society. To date, pharmacological treatments have obtained poor results and there is a growing interest in finding non-pharmacological interventions for this disease. Transcranial magnetic stimulation (TMS) is a non-invasive technique that is able to induce changes in brain activity and long-term modifications in impaired neural networks, becoming a promising clinical intervention. Our goal is to study the benefit of individualized TMS targeting based on the patient's functional connectivity (personalized targeting), and short duration TMS protocol, instead of current non-individualized and longer session approaches. A double blind randomized controlled trial will be conducted to assess the effects of TMS treatment immediately, 1 month, 3 months and 6 months after the end of the intervention. Fifty-four patients with a diagnosis of Alzheimer's disease will be randomly allocated into experimental (active TMS), sham cont...
Journal of Neural Transmission, 2011
The current drug treatment for Alzheimer's disease (AD) is only partially and temporary effective. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current inducing modulation in cortical excitability. In addition, cognitive training (COG) may improve cognitive functions in AD. Our aim was to treat AD patients combining high-frequency repetitive TMS interlaced with COG (rTMS-COG). Eight patients with probable AD, treated for more than 2 months with cholinesterase inhibitors, were subjected to daily rTMS-COG sessions (5/week) for 6 weeks, followed by maintenance sessions (2/week) for an additional 3 months. Six brain regions, located individually by MRI, were stimulated. COG tasks were developed to fit these regions. Primary objectives were average improvement of Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) and Clinical Global Impression of Change (CGIC) (after 6 weeks and 4.5 months, compared to baseline). Secondary objectives were average improvement of MMSE, ADAS-ADL, Hamilton Depression Scale (HAMILTON) and Neuropsychiatric Inventory (NPI). One patient abandoned the study after 2 months (severe urinary sepsis). ADAS-cog (average) improved by approximately 4 points after both 6 weeks and 4.5 months of treatment (P \ 0.01 and P \ 0.05) and CGIC by 1.0 and 1.6 points, respectively. MMSE, ADAS-ADL and HAMILTON improved, but without statistical significance. NPI did not change. No side effects were recorded. In this study, rTMS-COG (provided by Neuronix Ltd., Yokneam, Israel) seems a promising effective and safe modality for AD treatment, possibly as good as cholinesterase inhibitors. A European double blind study is underway.
Neurophysiologie Clinique, 2020
Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique used to modify cerebral cortex excitability and induce cognitive improvement [10]. Although Alzheimer's disease (AD) has a broad clinical spectrum of symptoms (not restricted to memory loss), most tDCS studies related to AD have focused on a single symptom, usually targeting one stimulation site (dorsolateral prefrontal cortex or temporal areas) [8]. In addition, no investigation has sought a long-term improvement via a multisite tDCS approach in AD patients. Here, we describe the cases of two AD patients who underwent an intermittent program of tDCS sessions over a 10-month period, applied to six cortical regions [2]. Patients were diagnosed with probable AD using NINCDS-ADRDA [7], and assessed one week before and after the intervention with the following scales: the Mini-Mental State Examination (MMSE) [4]; the Cornell Scale for Depression in Dementia (CSDD) [1]; the Blessed Dementia Scale (BDS) [3]; the Disability Assessment for Dementia (DAD) [5]; and the Neuropsychiatric Inventory (NPI) [6]. Case 1 was a 72-year-old man, with a history of hypertension and diabetes, who was taking donepezil (10 mg/daily), metformin (500 mg/daily) and amlodipine (5 mg/daily). At baseline, he had mild cognitive decline (MSSE = 21), dependence in activities of daily living (ADLs) (DAD = 22.5) and presence of anxiety, apathy and aberrant motor behavior (NPI = 18). Depressive symptoms, intellectual and personality deterioration showed a score of 7 on the CSDD and BDS. Case 2 was a 67-year-old woman, who was taking rivastigmine (4.6 mg/daily), irbesartan (75 mg/daily) and acetylsalicylic acid (81 mg/daily). The patient had mild cognitive decline (MMSE = 20), difficulty in solving problems, incapacity for self-care and impairment in ADLs (DAD = 15). She presented moderate symptoms of dysphoria, anxiety, depression and disinhibition (NPI = 22); mild depressive