Enhancing Cognition in Older Persons: A Randomized Controlled Trial of Mindfulness-Based Stress Reduction (MBSR) and Transcranial Direct Current Stimulation (tDCS).
Phase: NA
Conditions: Cognitive Impairment, Mild, Depressive Symptoms, Anxiety
Sponsor: Washington University School of Medicine

Thursday June 3rd, 2021 
 
TITLE: Enhancing Cognition in Older Persons: A Randomized Controlled Trial of 
Mindfulness-Based Stress Reduction (MBSR) and Transcranial Direct Current 
Stimulation (tDCS).   
 
NCT03653351 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

METHODS 
Study design and participants  
We conducted a randomized, double blind, sham-controlled trial of tDCS combined with 
MBSR in adults aged 60 years or older with symptoms of depression or anxiety plus 
subjective cognitive complaints in two academic centers (Centre for Addiction and 
Mental Health, Toronto, ON, Canada; and Washington University in St. Louis, MO, 
USA).  The study was approved by both institutional review boards and all participants 
provided written informed consent.  
 
Participants were recruited between June 27, 2018 and March 6, 2019. They completed 
an initial phone screen followed by an in-person screening assessment, which included a 
review of medical history and medications to determine eligibility.  Participants reported 
cognitive complaints but had intact cognitive function as ascertained by a Short Blessed 
Test [27] score ≤ 10 and a Montreal Cognitive Assessment (MoCA; [28]) score ≥ 25. The 
Patient Reported Outcomes Measurement Information System (PROMIS) measures were 
used to assess depression and anxiety over the past seven days [29] including self-
reported negative mood, views of self, social cognition, decreased positive affect, 
engagement self-reported fear, anxious misery, hyperarousal, and somatic symptoms 
related to arousal [30]. Participants were included if their baseline PROMIS 8-item 
depression score was ≥16 or their baseline PROMIS 7-item anxiety score was ≥14, 
indicating moderate to severe symptoms.  
 

Exclusion criteria included unstable medical illness, metal implants, significant 
neurological conditions, use of cognitive enhancers (e.g., donepezil) within the past 6 
weeks, use of anticonvulsants or antipsychotics (other than low-dose aripiprazole (< 2mg) 
or low dose gabapentin (< 100mg) if prescribed for pain), current cognitive training with 
brain training software, regular participation in mindfulness practice or yoga, IQ < 70 as 
estimated by the Wechsler Test of Adult Reading (WTAR; [31]), lifetime diagnosis of 
bipolar disorder, schizophrenia, schizoaffective disorder, or untreated post-traumatic 
stress disorder, or substance abuse within six months, as diagnosed by the Mini-
International Neuropsychiatric Interview (MINI; [32]). Participants meeting all eligibility 
criteria completed the baseline assessments, which included self-report and 
neuropsychological assessments of outcomes, listed below. 
 
Interventions 
All participants received MBSR; they were randomly assigned (1:1) to active or sham 
tDCS, using a permuted block approach to ensure treatment balance within each study 
site. Participants, MBSR instructors, and outcome raters were blinded to the tDCS 
condition (i.e., active vs. sham). Following the protocol of a large trial assessing the 
efficacy of combing tDCS with cognitive remediation in preventing dementia among 
older adults with mild cognitive impairment or remitted depression [33], active tDCS 
administration involved applying excitatory bilateral stimulation to the left and right 
DLPFC. To achieve this bilateral stimulation, the anode was placed at Fz and the cathode 
at Iz as per the 10-20 international electrode placement system. The tDCS was applied 
using a direct current of 2 mA (current density of 0.57 A/m2) for 30 minutes per day [33] 

during meditative practices of MBSR. The same parameters were used for sham 
stimulation, except the device shut off after 30 seconds of active stimulation. This brief 
period of active stimulation is not known to produce active neurological effects, but does 
ensure blinding because it is associated with common side effects of active tDCS, such as 
tingling and itching under the electrodes [34-36].   
 
Prior to the initiation of the intervention, all participants completed tDCS training 
provided at the local academic hospital using a group format. During five one-hour group 
sessions provided over five consecutive days, participants were given an overview of the 
tDCS device and detailed instructions for administration, programming, resetting, 
electrode placement, and safety procedures (such as aborting sessions safely). They were 
also trained on how to troubleshoot tDCS problems, such as managing side effects e.g. 
tingling and itching, and self-record necessary data. At the end of training, participants 
were required to demonstrate their competency self-administering tDCS by passing an 
assessment administered by the study coordinators.   Throughout the tDCS training 
sessions and the intervention trial, participants had access to a training video detailing the 
procedures to guide them through tDCS administration as needed. A manual and 
coordinator contact information was also provided to each participant, and the study 
coordinator was available to troubleshoot over the phone during at-home tDCS sessions.  
 
The MBSR training was based on the program developed by Jon Kabat-Zinn at the 
Center for Mindfulness University of Massachusetts Medical School [14, 15]. The in-
class MBSR training was conducted at the academic hospital using a group format over 

approximately ten weeks; group sessions included an orientation session, 8 weekly 2.5-
hour classes, and a half-day retreat. All participants were required to attend the MBSR in-
person classes and instructed to refrain from discussing tDCS treatment amongst 
themselves to protect blinding. Content included instruction in mindfulness meditation, 
mindful movements, and discussion of home practices to enhance mindfulness in 
everyday life. At the end of each in-class session, the MBSR instructor gave the group a 
structured MBSR activity and associated audio files to complete at home for the week. 
The study used “A Mindfulness-Based Stress Reduction Workbook” as a companion 
guide [37]. In summary, participants attended weekly in-class group MBSR plus tDCS 
sessions at the hospital, and then asked to complete at least 30 minutes of guided MBSR 
and tDCS at home the other six days of the week.  
  
 
Outcomes 
Trained research staff blinded to participants’ tDCS assignment performed pre- and post-
intervention assessments. Follow-up assessments were performed within two weeks of 
completing the intervention. Feasibility was assessed by examining participants’ in-class 
attendance (i.e., number of in-person MBSR group sessions attended) and adherence to 
at-home mindfulness practice while using tDCS. Participants completed hand-written 
logs daily, detailing their at-home use of tDCS and the frequency and duration of MBSR 
practice; these self-report logs were used to determine the at-home adherence rates.  To 
determine the at-home adherence rate, we first determined how many at-home sessions 
each participant completed by looking through the at-home logs. We then calculated the 

total expected number of sessions that should have been completed at home over the 
period of the intervention. Lastly, we divided the total number of sessions each 
participant completed by the total number of expected sessions to get a percentage of at-
home adherence. Participants also documented any failures of the tDCS device during 
stimulation and any adverse events (AEs). AEs that required the discontinuation of tDCS 
or MBSR were identified, as were serious adverse events (SAEs) defined as AEs that 
resulted in life-threatening health issues, hospitalization, or death.   
 
 
The main cognitive measure was the Fluid Cognition Composite from the National 
Institutes of Health (NIH) Toolbox Cognition Battery [38], a computer-based instrument 
measuring both crystalized and fluid cognition. In addition, immediate memory and 
delayed recall were measured using a standard 16-word list validated at the Washington 
University Alzheimer’s Disease Research Center that is sensitive to change and does not 
have ceiling effects in preliminary studies.  
 
 
The Cognitive Affective Mindfulness Scale – Revised (CAMS-R; [39]) was used to 
measure the four domains of mindfulness – attention, present-focus, awareness, and 
acceptance. CAMS-R is a self-report measure of everyday mindfulness that is not 
specific to any one type of meditation. CAMS-R asks questions about translating and 
integrating the domains of mindfulness into everyday life, for example, being able to 
focus on the present moment, and keeping track of one’s thoughts and feelings. CAMS-R 

was administered pre- and post-intervention to determine how well participants integrated 
the teachings from MBSR into their everyday lives. 
 
In addition to the PROMIS measures of depression and anxiety, the two following 
PROMIS measures were used to assess satisfaction with, and ability to perform usual 
social roles and activities: the 8-item short form v2.9 PROMIS Scale for Satisfaction with 
Social Roles and Activities [40] and the 8-item short form v2.0 PROMIS Ability to 
Participate in Social Roles and Activities [40].   
 
 
Statistical Analyses 
All data were analyzed using the Statistical Program for Social Sciences (SPSS) version 
25.0 [41]. Extreme outliers (±3 standard deviations) were removed for each time point. 
Data were visually inspected for normal distribution and were checked statistically with 
the Shapiro-Wilk test. Chi-square and independent samples t-tests were used to evaluate 
differences between the active and sham tDCS groups on baseline demographic, clinical, 
and cognitive measures. 
 
Measures of feasibility, tolerability, and safety were analyzed descriptively. While the 
primary goal of this pilot study was to assess feasibility, tolerability, and safety, 
preliminary evaluations of changes in efficacy measures were performed using repeated 
measures analyses of variance (RM-ANOVAs), with randomization as the between-
subjects variable, and time-point (pre- or post-intervention) as the within-subjects 

variable. For cognition, the three dependent variables were: NIH Toolbox Cognition 
Battery Fluid Cognition Composite, total recall score of the word list, and the delayed 
recall score of the word list. The effects of the intervention on subjective changes were 
explored with the following five dependent variables: CAMS-R, PROMIS depression 
scores, PROMIS anxiety scores, PROMIS satisfaction with social roles and activities, and 
PROMIS ability to participate in social roles and activities. For this pilot trial, a p < 0.05 
was considered significant and no corrections were made for multiple comparisons.