Home-based tDCS for Behavioral Symptoms in Alzheimer's Disease and Related Dementias (ADRD)
Phase: NA
Conditions: Alzheimer Disease
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Home-based tDCS for behavioral symptoms in Alzheimer's disease and related dementias 
 
NCT05478681 
 
Version Date: 08/27/2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
Protocol Title: Home-based tDCS for behavioral symptoms in Alzheimer's disease and 
related dementias 
Principal Investigator: Dr. Kendra M. Anderson, PhD, UTHealth 
Co-Investigators: 
Dr. Antonio Lucio Teixeira, UT Health San Antonio 
Dr. Thiago Macedo e Cordeiro, UT Health San Antonio 
Dr Holly Homes, UTHealth 
Dr Robert Suchting, UTHealth 
General Information 
Study Title 
Home-based tDCS for behavioral 
symptoms in Alzheimer's disease 
and related dementias (ADRD) 
Short Title 
tDCS for behavioral symptoms in 
ADRD 
Study 
Design 
This 
is   an  
  open-label, 
non-randomized  
clinical   trial to 
assess acceptability, safety and effi 
cacy of providing transcranial direct 
current 
 stimulation 
 (tDCS) 
to 
Alzheimer's disease and  related 
dementia   
 (ADRD)    
patients 
with behavioral symptoms. 
All participants will receive active 
tDCS 
with 
a 
constant 
current 
intensity of 2mA for 30 minutes, five 
times per week, for six weeks. 
Anodal tDCS will be applied to the 
left dorsolateral prefrontal cortex, 
while cathodal electrode will be 
positioned on the right dorsolateral 
prefrontal cortex. Caregivers will set 
up 
and 
administer 
tDCS 
for 
participants with AD at home. All 
sessions 
will 
be 
remotely 
supervised by trained research staff 
through 
video 
conferencing 
software. 
Participants 
will 
be 
assessed at baseline, treatment 
day 12, treatment day 28, treatment 
day 42, 
and 6 weeks 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
post-treatment. 
Study 
Participants 
Patients with ADRD and behavioral 
symptoms will  be  recruited   at  
the UTHealth 
Neurosciences 
Neurocognitive Disorders Center 
(Dr. Anderson), and UT Physicians 
Center for Healthy Aging (Dr. 
Holmes). 
Planned 
Sample Size 
20 
Planned 
Study Period 
12 weeks 
Objectives 
Outcome Measures 
Primary 
Goal 
To assess acceptability, and safety 
of providing tDCS to ADRD patients 
with behavioral symptoms. 
Acceptability will be evaluated using 
Likert  scale  (from  0 
[strongly 
disagree] to 10 [strongly agree]) to 
answer ten affirmatives regarding 
the use of home-based tDCS. 
Safety will be   assessed   with a 
questionnaire about side   effects 
that 
include    itching, 
 burning, 
headache, fatigue, and dizziness. 
Secondary 
Goal 
To assess the  efficacy  of  tDCS  
for ADRD-related symptoms, mainly 
behavioral symptoms. 
Behavioral and 
cognitive symptoms will 
be evaluated 
through validated clinical 
instruments. 
 
Background Information 
Alzheimer's disease (AD) is the main cause of dementia and one of the great 
challenges of the 21st century (1). An estimated 40 million people, mostly older than 60 
years, have dementia worldwide, and this number is expected to increase significantly 
in the next decades. Despite ongoing advances in the understanding of the 
pathogenesis of Alzheimer's disease and related dementias (ADRD), no treatment 
available can prevent or delay the cognitive decline that characterizes the condition (1). 
Besides cognitive impairment, nearly all patients with ADRD present behavioral and 
psychological symptoms, also called neuropsychiatric symptoms (NPS). 
NPS have been associated with negative outcomes in ADRD, including decrease of 
patient and caregiver quality of life, increased risk of institutionalization, higher costs 
and risk of mortality (2). The term NPS is an umbrella expression that encompasses 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
different types of behavioral problems, including agitation, apathy, delusion, insomnia, 
among others (3, 4). Due to the potential complications associated with the use of 
psychotropic drugs (e.g. increased risk of cerebrovascular events with antipsychotics, 
increased risk of falls and cognitive decline with benzodiazepines) and the limited 
evidence of their efficacy, clinical guidelines, medical organizations and expert groups 
recommend non-pharmacological strategies as the first-line treatment for NPS (5, 6). 
Transcranial direct current stimulation (tDCS) is a relatively novel non-
pharmacological method of neuromodulation that has been studied in several 
neuropsychiatric conditions with promising results in depression and negative 
symptoms of schizophrenia (7, 8). tDCS modulates brain activity through low-intensity 
electrical currents applied over the scalp, and has been associated with significant 
changes in network connectivity involving the prefrontal cortex and the cingulate cortex, 
regions implicated in the neural basis of NPS (9-11). 
In ADRD, a few controlled studies have been conducted to evaluate the role of tDCS 
on cognitive functioning. A systematic review and meta-analysis of these studies found 
that tDCS improved cognitive function in mild to moderate ADRD, but the stimulation 
parameters (multiple sites; single vs. repeated; lower vs. higher current) were very 
different among studies, not allowing definite conclusions (12) (13). Each patient 
received five   sessions/week    for    two    consecutive    weeks    totaling    10 
sessions. Recently, Im et al. (2019) investigated changes in cognitive performance, as 
assessed by the Mini Mental State Examination and other specific neuropsychological 
tests, after home-based 2 mA tDCS with anodal on the left dorsolateral prefrontal cortex 
(PFC) and cathodal on the right dorsolateral PFC for 30 minutes daily for 6 months in 
patients with early ADRD (14). Besides showing the feasibility of long-term home-based 
tDCS, these researchers found that daily tDCS sessions improve or stabilize cognitive 
decline in patients with ADRD. This clinical effect was associated with changes in 
regional cerebral metabolic rate for glucose in the left temporal lobe as assessed by 
18F-fluoro-2-deoxyglucose positron emission tomography (14). Altogether these studies 
suggest that tDCS is a promising tool for cognitive stabilization in ADRD. Only one  
study investigated the effect of tDCS on NPS in ADRD (15). Suemoto et al. (2014) 
studied 40 patients with ADRD who were randomized to receive either anodal tDCS (2 
mA constant current for 20 minutes) or sham-tDCS over the left dorsolateral prefrontal 
cortex (DLPFC) for six sessions during two weeks (16). While tDCS was safe in this 
population, there was no evidence of efficacy of tDCS on the NPS assessed. The lack 
of efficacy was attributed to several factors, especially the low number of sessions and 
the short period of intervention. One important aspect of this study was the challenge to 
engage participants in the trial mainly due to issues related to transportation to the 
medical center for tDCS application (16). Since patients with ADRD usually cannot drive 
safely, caregivers and/or family members need to be available to bring them into 
medical appointments. Home-based therapy would be very useful in this regard, as 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
patients would not need to attend clinic as often. 
Given the clinical relevance of NPS in ADRD, the equivocal results of the therapeutic 
resources available to address it, and the emerging evidence of safety and efficacy of 
tDCS in ADRD, our proposal aims to test the acceptability, safety and efficacy of home-
based tDCS for the treatment of NPS in ADRD. Home-based tDCS circumvents critical 
problems observed in previous trials (16), including the need of multiple visits to medical 
centers for tDCS application, allowing a more intensive application (e.g. 5 x per week) 
for long periods. 
 
Objectives 
Objectives 
Outcome Measures 
Primary objective 
Acceptability will 
be 
evaluated 
using 
To assess acceptability and safety of Likert scale (from 0 [strongly disagree] to 
providing 
tDCS 
to 
ADRD 
patients 10 [strongly agree]) to answer ten 
with behavioral symptoms. 
affirmatives 
regarding 
the 
use 
of 
home-based 
tDCS. Safety will 
be 
assessed with a questionnaire about side 
effects that include itching, burning, 
headache, fatigue, and dizziness. 
Acceptability scale will be applied on Week 
2, 4, 6 and 12. Side effects questionnaire will 
be applied on Week 2, 4 and 6. 
Secondary objectives 
Behavioral symptoms 
and 
cognitive 
To assess the efficacy of tDCS for measures evaluated through validated 
ADRD on 
clinical 
outcomes, tools: NPI, bDAS, CSDD, MMSE. 
mainly behavioral symptoms. 
NPI will be applied on Baseline, Week 2, 
4, 6 and 12, while bDAS, CSDD and 
MMSE will be applied on Baseline, Week 
6 and Week 12. 
 
Study Design 
 
We will carry out an open-label  study  to  evaluate  home-based  active  tDCS 
for AD and behavioral symptoms. There will be no randomization. All eligible patients 
will receive exactly the same treatment. All participants (n=20) will receive active tDCS 
with a constant current intensity of 2mA. Anodal tDCS will be applied to the left 
dorsolateral prefrontal cortex, while cathodal electrode will be positioned on the right 
dorsolateral prefrontal cortex. Caregivers will help setting up and administering tDCS for 
participants with AD at home. tDCS will be applied for 30min at an intensity of 2mA, with 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
30 s ramping up and down. 
 
We will target the stimulation on the dorsolateral prefrontal cortex based on the 
facts that prior studies showed positive results with this strategy for behavioral and 
cognitive symptoms of other neuropsychiatric disorders (17-19). According to previous 
home-based tDCS protocols (20, 21), all sessions will be remotely supervised by trained 
research staff (RA), therefore, the sessions will run from Monday through Friday for four 
consecutive weeks. The remote supervision of the sessions will be possible through 
video conferencing software (e.g., WebEx), and will ensure the use of proper technique 
and compliance to the study schedule, also monitoring any adverse events. The device 
(tDCS) will be programmed and cannot be tampered. Participants will be assessed at 
baseline,   treatment   day   14,   treatment   day   28, treatment   day 42-   and   6-
weeks post-treatment (Fig.1). The device will be delivered to patients at baseline and 
will be returned at the end of the treatment (week 6). 
 
 
 
 
Sample size 
Following recommendations in the statistical literature analyses we will proceed using 
parallel frequentist and Bayesian statistical inference. Frequentist analyses will provide 
conventional interpretation of the relationships between predictors and outcomes: the 
probability of the data, given the null hypothesis. Bayesian analyses will incrementally 
update specified prior information regarding effects to directly yield the probability of an 
alternative hypothesis. Bayesian analyses will employ weakly informative priors as a 
default (e.g., for regression coefficients: ~N[µ=0,σ2=100]). Sensitivity analyses using 
optimistic and pessimistic, skeptical priors will evaluate prior assumptions. Assessing 
the convergence of Bayesian analyses on the posterior distributions via Monte-Carlo 
Markov chain (MCMC) will use diagnostic evidence including effective sample size and 
scale reduction factors. Evaluation of posterior distributions will permit statements 
regarding the probability that effects of varying magnitudes exist, given the data, even 
with a small sample size. Frequentist analyses will evaluate all a priori models at the 
α=0.05 (two-tailed) significance level and will employ false discovery rate (FDR) to 
control for Type I error across any exploratory or post hoc analyses. Bayesian models 
will be evaluated via PP threshold guidelines in the literature suggesting that PP = 75% 
to 90% indicates moderate evidence, PP = 91% to 96% indicates strong evidence, and 
PP = 97% or above indicates very strong to extreme evidence. Bayesian analyses do 
not conceptualize Type I error in the same way as frequentist analyses due to formally 
calibrating probability in the prior distribution (as opposed to long-run probabilities, as in 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
frequentist analyses) and are less influenced by multiple comparisons in general due to 
observation of the Likelihood Principle. The current Bayesian analyses stipulate 
posterior probabilities ≥ 0.75 (equivalent to a Bayes factor = 0.33 or 3.0) that parameter 
estimates are greater or less than zero provide a minimum threshold of evidence to 
emphasize the value in discerning effects in a small study. The Bayesian inferential 
paradigm can provide probabilistic estimates of effects irrespective of sample size. 
Power considerations focus on identifying change over time from baseline to end-of-
treatment. Notably, the Bayesian analyses will provide the primary inferential results; 
thus considerations for the frequentist analyses are limited by the small sample size and 
provided solely as due diligence. Given alpha = 0.05, a sample size N = 20 provides 
80% power to detect an effect size Cohen's d = 0.66. 
 
Study Population  
A maximum of 20 persons with ADRD and clinically-meaningful behavioral 
symptoms will be enrolled in the study. This sample size is set to maximize the number 
of participants that may be enrolled over the time period of the proposal assuming a 
credible average recruitment rate, given the financial resources. 
Inclusion criteria. Participants who are 60 years or old will be considered 
eligible if they: (1) have ADRD and clinically-meaningful behavioral symptoms, (2) have 
a caregiver willing to participate in the study, (3) can speak and read English, (4) have 
stable doses of medications for at least one month. The diagnosis of ADRD will be 
verified by the investigators based on Mini-Mental Status Exam score (between 14 - 
25) (22, 23). Clinically-meaningful behavioral symptoms will be determined by the 
Neuropsychiatric Inventory (NPI), and defined as a total score ≥10 arising from at least 
two domains (24, 25). 
Exclusion    criteria. Participants will    be    excluded if    they    have:    (1)   
any unstable concurrent medical conditions, (2) history of brain surgery, seizure, or 
intracranial metal implantation, (3) current alcohol/substance use disorder. 
Recruitment and Retention. Participants will be recruited at the UTHealth 
Neurosciences Neurocognitive Disorders Center (Dr. Anderson), UT Physicians Center 
for Healthy Aging (Dr. Holmes), and at the UT Health San Antonio’s Glenn Biggs 
Institute for Alzheimer’s and Neurodegenerative diseases Neurology clinic (Dr. 
Teixeira). Study flyers with summary and contact information about the study will be 
used at the UTHealth Neurosciences Neurocognitive Disorders Center as a mean to 
provide awareness and information to potential participants. Flyers will be available at 
the request of potential subjects at the moment of their visit with Dr. Anderson, and at 
dedicated spaces for research recruitment material in the UTHealth Neurosciences 
Neurocognitive Disorders Center. As serious adverse effects and problems with the 
device use are not anticipated, it is expected a high retention rate. The remote 
supervision of the  tDCS  or  tDCS  sham  daily  sessions  by  trained  research  staff  
will contribute to the retention of subjects during the trial. 
Training plan. Patients will be instructed on treatment at baseline, when they will 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
receive the device. A trained research staff will instruct the participant's caregiver on 
how to handle the equipment. All sessions will be remotely supervised by trained 
research (RA) staff, who will be able to answer questions during the sessions and verify 
that the device is being used correctly. 
 
Study Procedures 
Primary Outcome 
Acceptability will be evaluated using the method proposed by Ahn et al. 
(2019) (21). Participants and/or their caretakers will be asked to apply a Likert scale 
(from 0 [strongly disagree] to 10 [strongly agree]) to answer ten affirmatives regarding 
the use of home-based tDCS. For example, question 1: It was easy to prepare the 
device and accessories, question 7: I felt confident using the device. Overall 
acceptability across groups will be evaluated by descriptive measures of satisfaction 
ratings. We expect that participant satisfaction ratings at the end of treatment will 
demonstrate high acceptance of tDCS treatment in the present sample. Acceptability 
scale will be applied on Week 2, 4, 6 and 12. 
Safety will be assessed with a questionnaire about side effects that include 
itching, burning, headache, fatigue, and dizziness (21). The most common side effects 
of tDCS reported in the literature are very mild and include tingling, burning sensation, 
and skin redness, while other less common side effects may include headache, 
sleepiness, dizziness, and difficulty concentrating (22-23). Although rare, a possible 
adverse event of tDCS is the occurrence of skin lesions or small skin burns on the site 
where electrodes touch the skin (24-25). The side effects questionnaire will be applied 
on Week 2, 4 and 6 to assess the incidence and frequency of side effects in our 
recruited sample. We expect that the occurrence of side effects will be similar to the 
frequencies reported in the scientific literature, demonstrating that home-based tDCS is 
a safe and feasible intervention to be used on the management of ADRD patients with 
behavioral symptoms. 
Secondary Outcome 
The main efficacy measure will be change on the Neuropsychiatric Inventory 
(NPI) score (26), the best-validated tool for measuring NPS in dementia patients. This 
12-item informant-based interview is a widely accepted  measure  of  NPS  in  
dementia. The NPI consists of a detailed evaluation of the following 12 neuropsychiatric 
domains: hallucinations, delusions, agitation/aggression, depression, anxiety, irritability, 
disinhibition, euphoria, apathy, aberrant motor behavior, change in night-time sleep 
behavior, and changes in appetite and eating (27). Each NPS domain is rated according 
to its severity (0-3) and frequency (0-4) (28). NPS will be assessed at baseline, during 
treatment  (weeks  2,  4  and  6)  and  6  weeks  post-treatment.  Our  hypothesis  is  
that patients receiving tDCS will demonstrate lower NPI scores at the end of treatment. 
Other clinical outcome measures will include: (1) total score on the Brief 
Dimensional Apathy Scale (bDAS) (29); (2) depressive symptoms as assessed by the 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
Cornell Scale for Depression in Dementia (CSDD) (30); (3) cognition as evaluated by 
the Mini-Mental State Examination (MMSE), which includes memory, language, praxis 
and orientation tasks, yielding a global cognition score ranging 0 to 30, with higher 
scores indicating better performance (31). Our hypothesis is that all participants 
receiving treatment will demonstrate lower scores on the bDAS and CSDD, and higher 
scores on the MMSE at the end of treatment. 
NPI will be applied on Baseline, Week 2, 4, 6 and 12, while bDAS, CSDD and MMSE will be applied 
on Baseline, Week 6 and Week 12. 
Sociodemographic and Clinical (health history, use of medication and  life  
habits) data (gender, age, marital status and education) will be collected at the  
baseline. 
 
Assessment 
Baseline 
Week 2 
Week 4 
Week 6 
Week 12 
Medical History Questionnaire 
X 
MMSE (Secondary outcome) 
X 
X 
X 
NPI (Secondary outcome) 
X 
X 
X 
X 
X 
bDAS (Secondary outcome) 
X 
X 
X 
CSDD (Secondary outcome) 
X 
X 
X 
tDCS experience questionnaire (Primary outcome) 
X 
X 
X 
X 
Side effects questionnaire (Primary outcome) 
X 
X 
X 
 
Table 1. Timetable for Collection of Data 
 
 
Data and Safety Monitoring 
Data will be collected from 20 human participants, and all information will be de-
identified in order to protect their confidentiality. All clinical information will be stored in 
dedicated files at UT Health Department of Psychiatry and Behavioral Sciences. The 
data generated in this project will be presented at national or international conferences 
and published in a timely fashion. 
 
Statistics 
Statistical modeling will primarily use generalized linear modeling (GLM) with multilevel 
components (GLMM) for correlated observations. Potentially nonlinear relationships 
between predictors and outcomes will be evaluated via inclusion of polynomial or spline 
effects. Continuous, dichotomous, and count-distributed data will utilize linear, logistic, 
and Poisson/negative binomial regression, respectively (each with a canonical link 
function). Evaluation of distributional assumptions will use residual plots, formal 
statistical tests, and posterior predictive checking. Violations of assumptions will be 
addressed via transformation, robust estimation, stratification, and/or coefficient scaling 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
where appropriate. Statistical analyses will be performed using the R statistical 
computing environment via packages lme, rstan, and brms. 
 
 
Ethics/Protection of Patient Confidentiality  
The sample of this study consists of 20 older adults aged 60 years-old and over 
with ADRD and behavioral symptoms. Study participants or their legally authorized 
representatives will give informed consent. Moreover, caregivers and/or relatives will be 
required to be present during the clinical assessments and tDCS sessions to ensure 
reliable information and proper use of the device. Participants will be recruited without 
any specific regard to sex, race, religion or ethnicity. Patients will be recruited at the 
UTHealth Neurosciences Neurocognitive Disorders Center, and UTHealth Center for 
Healthy Aging. We will recruit ADRD patients whose dementia is of mild to moderate 
severity. Adults younger than 60, adolescents and children are excluded as we are 
focusing on dementia, an age-related disorder that usually affects individuals aged 60 
and older. No other special classes of vulnerable individuals will be included. It is 
anticipated that the subject demographic profile will mirror the larger population of 
individuals with ADRD from which they are recruited. 
Informed Consent and Assent. Potential subjects and their caregivers/relatives 
will be informed about the study purpose, procedures, risks and benefits. They will be 
informed that participation in the research study is voluntary and that they are free to 
decline to be in the study, or to withdraw from it at any point. Study records will be kept 
confidential. Study information will be coded, and only study personnel will have access 
to the files. 
Protection Against Potential Risks. The risks to the subjects involved in  this 
study are minimal. To ensure this, we will take necessary steps to reduce risk for all 
study participants. We will try to create an atmosphere of security and trust prior any 
clinical assessment in order to minimize any discomfort with the research questions. In 
addition, subjects are always given permission to not answer questions with which they 
feel uncomfortable. A number of procedures (e.g. use of identifying numbers instead of 
names) will be implemented to protect subjects against loss of confidentiality. Side 
effects related to active tDCS application are uncommon, and mild when present, 
including: itching and burning sensation on the scalp, mild headache, dizziness, and 
fatigue. Although rare, a possible adverse event of tDCS is the occurrence of skin 
lesions or small skin burns on the site where electrodes touch the skin (24-25). 
Potential   Benefits   to   Research   Participants. If    our    hypothesis    is 
correct, all subjects might benefit from the study participation. Importantly, the results 
will be relevant to the field of AD and neuromodulation. 
 
Significance 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
Our proposal will address a frequent and sometimes overlooked clinical problem 
in patients with ADRD, i.e. behavioral symptoms. The proposal can advance the field of 
non-pharmacological strategies for NPS, also presenting a great potential for clinical 
translation. Home-based intervention with real-time monitoring through a secure 
conferencing platform is a new modality for improving symptom management in ADRD. 
Moreover, home-based, remotely supervised tDCS has advantages over clinic-based 
sessions, considering the time and cost associated with attending multiple sessions 
over several days. Caregivers will be trained at the in-person baseline visit, and all the 
tDCS sessions will be remotely supervised via secure videoconferencing software by 
trained research staff for the entire duration of each session to ensure the use of proper 
technique and to monitor any adverse events. 
 
 
Costs and Compensations 
Participants will not be charged for tests, procedures or other costs incurred 
solely for the purposes of this research. Patients will receive a voucher of US 50.00 for 
their time dedicated to each evaluation (total number of assessments = 5). 
 
 
Publication Plan 
This study will represent an original contribution to the areas of non-
pharmacological approaches for NPS in ADRD and neuromodulation. The results will be 
presented in national and international meetings, and published as a research 
manuscript. 
 
References 
 
1. 
Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, et al. 
Alzheimer's disease. Lancet. 2016;388(10043):505-17. 
2. 
Cummings J, Ritter A, Rothenberg K. Advances in Management of Neuropsychiatric 
Syndromes in Neurodegenerative Diseases. Curr Psychiatry Rep. 2019;21(8):79. 
3. 
Masopust J, Protopopova D, Valis M, Pavelek Z, Klimova B. Treatment of behavioral 
and psychological symptoms of dementias with psychopharmaceuticals: a review. 
Neuropsychiatr Dis Treat. 2018;14:1211-20. 
4. 
Canevelli M, Adali N, Voisin T, Soto ME, Bruno G, Cesari M, et al. Behavioral and 
psychological subsyndromes in Alzheimer's disease using the Neuropsychiatric Inventory. 
International journal of geriatric psychiatry. 2013;28(8):795-803. 
5. 
Dyer SM, Harrison SL, Laver K, Whitehead C, Crotty M. An overview of systematic 
reviews of pharmacological and non-pharmacological interventions for the treatment of 
behavioral and psychological symptoms of dementia. Int Psychogeriatr. 2018;30(3):295-309. 
6. 
Abraha I, Rimland JM, Trotta FM, Dell'Aquila G, Cruz-Jentoft A, Petrovic M, et al. 
Systematic review of systematic reviews of non-pharmacological interventions to treat 
behavioural disturbances in older patients with dementia. The SENATOR-OnTop series. BMJ 
Open. 2017;7(3):e012759. 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
7. 
Razza LB, Palumbo P, Moffa AH, Carvalho AF, Solmi M, Loo CK, et al. A systematic 
review and meta-analysis on the effects of transcranial direct current stimulation in depressive 
episodes. Depress Anxiety. 2020. 
8. 
Valiengo L, Goerigk S, Gordon PC, Padberg F, Serpa MH, Koebe S, et al. Efficacy and 
Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in 
Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2019. 
9. 
Guimaraes HC, Levy R, Teixeira AL, Beato RG, Caramelli P. Neurobiology of apathy in 
Alzheimer's disease. Arq Neuropsiquiatr. 2008;66(2B):436-43. 
10. 
Pena-Gomez C, Sala-Lonch R, Junque C, Clemente IC, Vidal D, Bargallo N, et al. 
Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by 
resting-state functional MRI. Brain Stimul. 2012;5(3):252-63. 
11. 
Kazui H, Takahashi R, Yamamoto Y, Yoshiyama K, Kanemoto H, Suzuki Y, et al. Neural 
Basis of Apathy in Patients with Amnestic Mild Cognitive Impairment. J Alzheimers Dis. 
2017;55(4):1403-16. 
12. 
Cai M, Guo Z, Xing G, Peng H, Zhou L, Chen H, et al. Transcranial Direct Current 
Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A 
Meta-Analysis. Alzheimer Dis Assoc Disord. 2019;33(2):170-8. 
13. 
Khedr EM, Salama RH, Abdel Hameed M, Abo Elfetoh N, Seif P. Therapeutic Role of 
Transcranial Direct Current Stimulation in Alzheimer Disease Patients: Double-Blind, 
Placebo-Controlled Clinical Trial. Neurorehabil Neural Repair. 2019;33(5):384-94. 
14. 
Im JJ, Jeong H, Bikson M, Woods AJ, Unal G, Oh JK, et al. Effects of 6-month at-home 
transcranial direct current stimulation on cognition and cerebral glucose metabolism in 
Alzheimer's disease. Brain Stimul. 2019;12(5):1222-8. 
15. 
Vacas SM, Stella F, Loureiro JC, Simoes do Couto F, Oliveira-Maia AJ, Forlenza OV. 
Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A 
systematic review and meta-analysis. Int J Geriatr Psychiatry. 2019;34(9):1336-45. 
16. 
Suemoto CK, Apolinario D, Nakamura-Palacios EM, Lopes L, Leite RE, Sales MC, et al. 
Effects of a non-focal plasticity protocol on apathy in moderate Alzheimer's disease: a 
randomized, double-blind, sham-controlled trial. Brain Stimul. 2014;7(2):308-13. 
17. 
Triggs WJ, Ricciuti N, Ward HE, Cheng J, Bowers D, Goodman WK, et al. Right and left 
dorsolateral pre-frontal rTMS treatment of refractory depression: A randomized, sham-controlled 
trial. Psychiatry Research. 2010;178(3):467-74. 
18. 
Mishra BR, Nizamie SH, Das B, Praharaj SK. Efficacy of repetitive transcranial magnetic 
stimulation in alcohol dependence: a sham-controlled study. Addiction. 2010;105(1):49-55. 
19. 
Tayeb Y, Lavidor M. Enhancing switching abilities: Improving practice effect by 
stimulating the dorsolateral pre frontal cortex. Neuroscience. 2016;313:92-8. 
20. 
Ahn H, Sorkpor S, Miao H, Zhong C, Jorge R, Park L, et al. Home-based 
self-administered transcranial direct current stimulation in older adults with knee osteoarthritis 
pain: An open-label study. Journal of clinical neuroscience : official journal of the Neurosurgical 
Society of Australasia. 2019;66:61-5. 
21. 
Ahn H, Zhong C, Miao H, Chaoul A, Park L, Yen IH, et al. Efficacy of combining 
home-based transcranial direct current stimulation with mindfulness-based meditation for pain in 
older adults with knee osteoarthritis: A randomized controlled pilot study. Journal of clinical 
neuroscience : official journal of the Neurosurgical Society of Australasia. 2019;70:140-5. 
22. 
Inagawa T, Yokoi Y, Narita Z, Maruo K, Okazaki M, Nakagome K. Safety and feasibility 
of transcranial direct current stimulation for cognitive rehabilitation in patients with mild or major 
neurocognitive disorders: A randomized sham-controlled pilot study. Front Hum Neurosci. 
2019;13:273. 
23. 
Yang CL, Qu Y, Huang JP, Wang TT, Zhang H, Chen Y, Tan YC. Efficacy and safety of 
transcranial direct current stimulation in the treatment of fibromyalgia: A systematic review and 
meta-analysis. Neurophysiol Clin. 2024;54(1):102944. 

IRB NUMBER: HSC-MS-22-0296 
IRB APPROVAL DATE: 08/27/2024 
 
24. 
Lu H, Chan SSM, Chan WC, Lin C, Cheng CPW, Linda Chiu Wa L. Randomized 
controlled trial of TDCS on cognition in 201 seniors with mild neurocognitive disorder. Ann Clin 
Transl Neurol. 2019;6(10):1938-1948. 
25. 
Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, Cohen LG, 
Dowthwaite G, Ellrich J, Flöel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, 
Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, 
Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, 
Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, 
Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: 
Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 
2017;128(9):1774-1809. 
26. 
Cummings JLMD. The Neuropsychiatric Inventory: Assessing psychopathology in 
dementia patients. Neurology. 1997;48(5) Supplement(6):10S-6S. 
27. 
Balthazar MLF, Pereira FRS, Lopes TM, da Silva EL, Coan AC, Campos BM, et al. 
Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity 
alterations in the salience network. Human Brain Mapping. 2014;35(4):1237-46. 
28. 
Eikelboom WS, van den Berg E, Singleton EH, Baart SJ, Coesmans M, Leeuwis AE, et 
al. Neuropsychiatric and Cognitive Symptoms Across the Alzheimer Disease Clinical Spectrum: 
Cross-sectional and Longitudinal Associations. Neurology. 2021;97(13):e1276-e87. 
29. 
Radakovic R, Gray D, Dudley K, Mioshi E, Dick D, Melchiorre G, et al. Reliability and 
validity of the brief dimensional apathy scale. Archives of clinical neuropsychology : the official 
journal of the National Academy of Neuropsychologists. 2020;35(5):539-44. 
30. 
Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in 
Dementia. Biol Psychiatry. 1988;23(3):271-84. 
31. 
Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for 
grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-98.