Alzheimer's Disease, Frontotemporal Dementia, Behavioral Variant
Conditions
Brief summary
This pilot study aims to test clinical and connectivity changes following non-invasive stimulation of disease-specific networks in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Brain network stimulation will be carried out with transcranial direct current stimulation (tDCS). Target networks will be the default mode network (DMN) and salience network (SN). Twenty AD and 20 bvFTD patients will be recruited and assessed with a comprehensive clinical, behavioral and cognitive battery, and 3 Tesla MRI scan (including resting-state functional MRI, arterial spin labeling, diffusion tensor imaging, structural MRI) at three time-points: baseline, after tDCS, and after 6 months. Patients will be randomized to 2 arms: anodal stimulation of the disease-specific network (DMN in AD, SN in bvFTD) or cathodal stimulation of the anti-correlated network (SN in AD, DMN in bvFTD). The intervention will consist of 10 tDCS sessions over two weeks. Cerebrospinal fluid (CSF) samples will be collected at baseline for biomarker's assessment; blood samples will be collected at each time-point to assess changes in peripheral inflammatory markers. Blood and CSF collection will be optional. A sample of 20 elderly controls will be included for baseline comparisons.
Interventions
DEVICEtranscranial direct current stimulation (tDCS)
10 daily 25-minutes tDCS sessions over two weeks.
Sponsors
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of AD or bvFTD according to current clinical criteria (Albert et al., 2011; Rascovsky et al., 2011) * Ability to provide written informed consent * Availability of a collateral source
Exclusion criteria
* Moderate/severe dementia * Presence of any medical or psychiatric illness that could interfere in completing assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Disease Severity (CDR) | Baseline, post tDCS (week 3) | CDR - Clinical Dementia Rating score The clinical dementia rating (CDR) is a clinical global rating scale administered to both the participant and the caregiver, assessing 6 domains of participant function: memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care. Each domain is based on a 5-point scale ranging from no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 to severe impairment=3. The global CDR score is computed via a memory-weighted averaging algorithm of the six domain scores and ranges from 0 to 5. The CDR-sum of boxes (CDR-SB) is the sum of the individual domain scores and ranges from 0 to 18. Higher scores indicate more clinical impairment. Negative changes at post tDCS compared to baseline represent an improvement on the scale. |
| Change in Behavioral Symptom Severity (NPI) | Baseline, post tDCS (week 3) | The Neuropsychiatric Inventory (NPI) is a behavioral scale administered to the caregiver assessing 12 dimensions: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, nighttime behaviors, and appetite/eating. Each dimension has multiple screening questions relating to symptoms. If the answer to the screening questions is Yes, the dimensional-score is the product of frequency (1=occasionally to 4=very frequently) and severity (1=Mild to 3=Severe) of symptoms. Dimensional-scores are summed (from 0 to 144). Higher scores indicate greater behavioral disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale. |
| Change in Behavioral Symptom Severity (FBI) | Baseline, post tDCS (week 3) | The Frontal Behavioral Inventory (FBI) is a 24-item inventory designed to assess behavior and personality changes via caregiver. Item-level scores range from 0=none, 1=mild/occasional, 2=moderate, 3=severe/most of the time. Item-scores are summed (from 0 to 72). Higher scores indicate greater behavioral/personality disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale. |
| Change in Functional Connectivity | Baseline, post tDCS (week 3) | Default mode network (DMN) and salience network (SN) mean functional connectivity is assessed on resting state functional MRI. Functional connectivity is standardized to Z scores and thresholded at Z\>2. Higher values denote greater functional connectivity. A positive change at post tDCS compared to baseline represents an increase in resting-state functional connectivity. |
| Change in Cerebral Blood Flow | Baseline, post tDCS (week 3) | Default mode network (DMN) and salience network (SN) mean cerebral blood flow is assessed on arterial spin labeling. Cerebral blood flow is computed by averaging values across the DMN and SN regions of interest. Cerebral blood flow is a measure of brain perfusion, higher values denoting higher perfusion. A positive change at post tDCS compared to baseline represents an increase in perfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Structural Connectivity: FA | Baseline, post tDCS (week 3) | Fractional anisotropy (FA) is assessed on diffusion weighted imaging. FA values are averaged in default mode network (DMN) and salience network (SN) regions of interest. FA values denote the directionality of water diffusivity, ranging from 0 (isotropic diffusion) to 1 (anisotropic diffusion). Higher values denote higher directionality and connectivity. Positive changes at post tDCS compared to baseline represent an improvement in the measure. |
| Change in Cognition: Memory | Baseline, post tDCS (week 3) | The composite memory score consists of the averaged Z-standardized scores of 5 memory tests: immediate and delayed auditory verbal learning test recall, Rey-Osterrieth complex figure recall, story recall, digit span backward and forward tests. Each test score is normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better memory performance. Positive changes at post tDCS compared to baseline represent an improvement in memory. |
| Change in Structural Connectivity: MD, AxD, RaD | Baseline, post tDCS (week 3) | Mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RaD) are assessed on diffusion weighted imaging. MD, AxD, RaD values are averaged in default mode network (DMN) and salience network (SN) regions of interest. MD, AxD, and RaD measure water diffusion and are expressed in mm\^2/s (starting from 0 with no maximum value; scaled at x10\^-3). Higher values denote higher diffusion and lower connectivity. Negative changes at post tDCS compared to baseline represent an improvement in the measure. |
| Change in Cognition: Language | Baseline, post tDCS (week 3) | The composite language score consists of the averaged Z-standardized scores of 2 language tests: verbal fluency and token tests. Each test score is normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better language performance. Positive changes at post tDCS compared to baseline represent an improvement in language. |
| Change in Cognition: Executive Function | Baseline, post tDCS (week 3) | The composite executive function score consists of the averaged Z-standardized scores of 2 executive functions tests: trail making test part A and part B tests. Each test score is normalized to an independent dataset of healthy controls and inverted. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better executive function performance. Positive changes at post tDCS compared to baseline represent an improvement in executive functions. |
| Change in Cognition: Visuospatial Function | Baseline, post tDCS (week 3) | The visuospatial function score consists of the Z-standardized scores for the Rey-Osterrieth complex figure copy test. Scores are normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better visuospatial performance. Positive changes at post tDCS compared to baseline represent an improvement in visuospatial functions. |
| Change in Cognition: Emotion Recognition | Baseline, post tDCS (week 3) | The composite emotion recognition score consists of the averaged Z-standardized scores for 2 emotion recognition tests: reading the Mind in the Eyes and 60 Ekman faces tests. Each test score is normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better emotion recognition performance. Positive changes at post tDCS compared to baseline represent an improvement in emotion recognition. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AD: Anodal tDCS of the DMN AD: anodal tDCS of the default mode (DMN) network with transcranial direct current stimulation (tDCS): 10 daily 25-minutes tDCS sessions over two weeks.
Stimulation target: inferior parietal cortex | 10 |
| AD: Cathodal tDCS of the SN AD: cathodal tDCS of the salience network (SN) with transcranial direct current stimulation (tDCS): 10 daily 25-minutes tDCS sessions over two weeks.
Stimulation target: prefrontal cortex | 10 |
| bvFTD: Anodal tDCS of the SN bvFTD: anodal tDCS of the salience network (SN) with transcranial direct current stimulation (tDCS): 10 daily 25-minutes tDCS sessions over two weeks.
Stimulation target: prefrontal cortex | 10 |
| bvFTD: Cathodal tDCS of the DMN bvFTD: cathodal tDCS of the default mode network (DMN) with transcranial direct current stimulation (tDCS): 10 daily 25-minutes tDCS sessions over two weeks.
Stimulation target: inferior parietal cortex | 10 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up | Adverse Event | 0 | 0 | 0 | 1 |
| Follow-up | Withdrawal by Subject | 0 | 0 | 0 | 1 |
| Intervention | Adverse Event | 0 | 1 | 0 | 1 |
| Intervention | safety (psoriasis, cortical vascular lesions on MRI) | 1 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | bvFTD: Cathodal tDCS of the DMN | Total | bvFTD: Anodal tDCS of the SN | AD: Cathodal tDCS of the SN | AD: Anodal tDCS of the DMN |
|---|---|---|---|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 11 | 71 years STANDARD_DEVIATION 8 | 71 years STANDARD_DEVIATION 10 | 73 years STANDARD_DEVIATION 6 | 72 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 40 Participants | 10 Participants | 10 Participants | 10 Participants |
| Region of Enrollment Italy | 10 Participants | 40 Participants | 10 Participants | 10 Participants | 10 Participants |
| Sex/Gender, Customized Female | 5 Participants | 18 Participants | 3 Participants | 4 Participants | 6 Participants |
| Sex/Gender, Customized Male | 5 Participants | 22 Participants | 7 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 5 / 11 | 6 / 11 | 5 / 12 | 5 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 12 | 1 / 11 |
Outcome results
Primary
Change in Behavioral Symptom Severity (FBI)
The Frontal Behavioral Inventory (FBI) is a 24-item inventory designed to assess behavior and personality changes via caregiver. Item-level scores range from 0=none, 1=mild/occasional, 2=moderate, 3=severe/most of the time. Item-scores are summed (from 0 to 72). Higher scores indicate greater behavioral/personality disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Behavioral Symptom Severity (FBI) | -2 score on a scale | Standard Deviation 4 |
| AD: Cathodal tDCS of the SN | Change in Behavioral Symptom Severity (FBI) | -4 score on a scale | Standard Deviation 8 |
Primary
Change in Behavioral Symptom Severity (NPI)
The Neuropsychiatric Inventory (NPI) is a behavioral scale administered to the caregiver assessing 12 dimensions: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, nighttime behaviors, and appetite/eating. Each dimension has multiple screening questions relating to symptoms. If the answer to the screening questions is Yes, the dimensional-score is the product of frequency (1=occasionally to 4=very frequently) and severity (1=Mild to 3=Severe) of symptoms. Dimensional-scores are summed (from 0 to 144). Higher scores indicate greater behavioral disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Behavioral Symptom Severity (NPI) | -1 score on a scale | Standard Deviation 3 |
| AD: Cathodal tDCS of the SN | Change in Behavioral Symptom Severity (NPI) | -3 score on a scale | Standard Deviation 6 |
| bvFTD: Anodal tDCS of the SN | Change in Behavioral Symptom Severity (NPI) | -1 score on a scale | Standard Deviation 4 |
| bvFTD: Cathodal tDCS of the DMN | Change in Behavioral Symptom Severity (NPI) | -6 score on a scale | Standard Deviation 11 |
Primary
Change in Cerebral Blood Flow
Default mode network (DMN) and salience network (SN) mean cerebral blood flow is assessed on arterial spin labeling. Cerebral blood flow is computed by averaging values across the DMN and SN regions of interest. Cerebral blood flow is a measure of brain perfusion, higher values denoting higher perfusion. A positive change at post tDCS compared to baseline represents an increase in perfusion.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Cerebral Blood Flow | SN | 4.37 ml/100g/min | Standard Deviation 7 |
| AD: Anodal tDCS of the DMN | Change in Cerebral Blood Flow | DMN | 4.87 ml/100g/min | Standard Deviation 8.92 |
| AD: Cathodal tDCS of the SN | Change in Cerebral Blood Flow | SN | -1.92 ml/100g/min | Standard Deviation 12.3 |
| AD: Cathodal tDCS of the SN | Change in Cerebral Blood Flow | DMN | -0.06 ml/100g/min | Standard Deviation 9.46 |
| bvFTD: Anodal tDCS of the SN | Change in Cerebral Blood Flow | DMN | 0.56 ml/100g/min | Standard Deviation 7.72 |
| bvFTD: Anodal tDCS of the SN | Change in Cerebral Blood Flow | SN | 2.34 ml/100g/min | Standard Deviation 4.84 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cerebral Blood Flow | DMN | 3.08 ml/100g/min | Standard Deviation 3.45 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cerebral Blood Flow | SN | 1.41 ml/100g/min | Standard Deviation 4.09 |
Primary
Change in Clinical Disease Severity (CDR)
CDR - Clinical Dementia Rating score The clinical dementia rating (CDR) is a clinical global rating scale administered to both the participant and the caregiver, assessing 6 domains of participant function: memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care. Each domain is based on a 5-point scale ranging from no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 to severe impairment=3. The global CDR score is computed via a memory-weighted averaging algorithm of the six domain scores and ranges from 0 to 5. The CDR-sum of boxes (CDR-SB) is the sum of the individual domain scores and ranges from 0 to 18. Higher scores indicate more clinical impairment. Negative changes at post tDCS compared to baseline represent an improvement on the scale.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Clinical Disease Severity (CDR) | CDR global | -0.1 score on a scale | Standard Deviation 0.2 |
| AD: Anodal tDCS of the DMN | Change in Clinical Disease Severity (CDR) | CDR sum of boxes | 0.1 score on a scale | Standard Deviation 0.4 |
| AD: Cathodal tDCS of the SN | Change in Clinical Disease Severity (CDR) | CDR sum of boxes | 0.0 score on a scale | Standard Deviation 0.2 |
| AD: Cathodal tDCS of the SN | Change in Clinical Disease Severity (CDR) | CDR global | 0.0 score on a scale | Standard Deviation 0 |
| bvFTD: Anodal tDCS of the SN | Change in Clinical Disease Severity (CDR) | CDR global | 0.0 score on a scale | Standard Deviation 0 |
| bvFTD: Anodal tDCS of the SN | Change in Clinical Disease Severity (CDR) | CDR sum of boxes | -0.1 score on a scale | Standard Deviation 0.3 |
| bvFTD: Cathodal tDCS of the DMN | Change in Clinical Disease Severity (CDR) | CDR global | 0.0 score on a scale | Standard Deviation 0 |
| bvFTD: Cathodal tDCS of the DMN | Change in Clinical Disease Severity (CDR) | CDR sum of boxes | 0.0 score on a scale | Standard Deviation 0 |
Primary
Change in Functional Connectivity
Default mode network (DMN) and salience network (SN) mean functional connectivity is assessed on resting state functional MRI. Functional connectivity is standardized to Z scores and thresholded at Z\>2. Higher values denote greater functional connectivity. A positive change at post tDCS compared to baseline represents an increase in resting-state functional connectivity.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Functional Connectivity | DMN | 0.08 Z-score | Standard Deviation 0.13 |
| AD: Anodal tDCS of the DMN | Change in Functional Connectivity | SN | -0.06 Z-score | Standard Deviation 0.15 |
| AD: Cathodal tDCS of the SN | Change in Functional Connectivity | SN | 0.05 Z-score | Standard Deviation 0.2 |
| AD: Cathodal tDCS of the SN | Change in Functional Connectivity | DMN | -0.09 Z-score | Standard Deviation 0.11 |
| bvFTD: Anodal tDCS of the SN | Change in Functional Connectivity | DMN | -0.02 Z-score | Standard Deviation 0.23 |
| bvFTD: Anodal tDCS of the SN | Change in Functional Connectivity | SN | 0.08 Z-score | Standard Deviation 0.18 |
| bvFTD: Cathodal tDCS of the DMN | Change in Functional Connectivity | DMN | -0.04 Z-score | Standard Deviation 0.15 |
| bvFTD: Cathodal tDCS of the DMN | Change in Functional Connectivity | SN | 0.02 Z-score | Standard Deviation 0.12 |
Secondary
Change in Cognition: Emotion Recognition
The composite emotion recognition score consists of the averaged Z-standardized scores for 2 emotion recognition tests: reading the Mind in the Eyes and 60 Ekman faces tests. Each test score is normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better emotion recognition performance. Positive changes at post tDCS compared to baseline represent an improvement in emotion recognition.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Cognition: Emotion Recognition | 0.1 z score | Standard Deviation 0.5 |
| AD: Cathodal tDCS of the SN | Change in Cognition: Emotion Recognition | 0.1 z score | Standard Deviation 0.6 |
| bvFTD: Anodal tDCS of the SN | Change in Cognition: Emotion Recognition | 0.3 z score | Standard Deviation 1.2 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cognition: Emotion Recognition | 0.1 z score | Standard Deviation 0.9 |
Secondary
Change in Cognition: Executive Function
The composite executive function score consists of the averaged Z-standardized scores of 2 executive functions tests: trail making test part A and part B tests. Each test score is normalized to an independent dataset of healthy controls and inverted. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better executive function performance. Positive changes at post tDCS compared to baseline represent an improvement in executive functions.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Cognition: Executive Function | 0.3 z score | Standard Deviation 2.9 |
| AD: Cathodal tDCS of the SN | Change in Cognition: Executive Function | -0.3 z score | Standard Deviation 2.4 |
| bvFTD: Anodal tDCS of the SN | Change in Cognition: Executive Function | 0.7 z score | Standard Deviation 2.3 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cognition: Executive Function | -0.7 z score | Standard Deviation 1.6 |
Secondary
Change in Cognition: Language
The composite language score consists of the averaged Z-standardized scores of 2 language tests: verbal fluency and token tests. Each test score is normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better language performance. Positive changes at post tDCS compared to baseline represent an improvement in language.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Cognition: Language | 0.7 z score | Standard Deviation 0.6 |
| AD: Cathodal tDCS of the SN | Change in Cognition: Language | 0.4 z score | Standard Deviation 0.6 |
| bvFTD: Anodal tDCS of the SN | Change in Cognition: Language | 0.7 z score | Standard Deviation 0.9 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cognition: Language | 0.4 z score | Standard Deviation 0.6 |
Secondary
Change in Cognition: Memory
The composite memory score consists of the averaged Z-standardized scores of 5 memory tests: immediate and delayed auditory verbal learning test recall, Rey-Osterrieth complex figure recall, story recall, digit span backward and forward tests. Each test score is normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better memory performance. Positive changes at post tDCS compared to baseline represent an improvement in memory.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Cognition: Memory | 0.3 z score | Standard Deviation 0.2 |
| AD: Cathodal tDCS of the SN | Change in Cognition: Memory | 0.3 z score | Standard Deviation 0.3 |
| bvFTD: Anodal tDCS of the SN | Change in Cognition: Memory | 0.1 z score | Standard Deviation 0.3 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cognition: Memory | 0.2 z score | Standard Deviation 0.3 |
Secondary
Change in Cognition: Visuospatial Function
The visuospatial function score consists of the Z-standardized scores for the Rey-Osterrieth complex figure copy test. Scores are normalized to an independent dataset of healthy controls. Z-scores have no minimum/maximum values. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values denote better visuospatial performance. Positive changes at post tDCS compared to baseline represent an improvement in visuospatial functions.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Cognition: Visuospatial Function | 1.2 z score | Standard Deviation 1.1 |
| AD: Cathodal tDCS of the SN | Change in Cognition: Visuospatial Function | 0.0 z score | Standard Deviation 1.6 |
| bvFTD: Anodal tDCS of the SN | Change in Cognition: Visuospatial Function | 0.1 z score | Standard Deviation 0.8 |
| bvFTD: Cathodal tDCS of the DMN | Change in Cognition: Visuospatial Function | 0.4 z score | Standard Deviation 0.9 |
Secondary
Change in Structural Connectivity: FA
Fractional anisotropy (FA) is assessed on diffusion weighted imaging. FA values are averaged in default mode network (DMN) and salience network (SN) regions of interest. FA values denote the directionality of water diffusivity, ranging from 0 (isotropic diffusion) to 1 (anisotropic diffusion). Higher values denote higher directionality and connectivity. Positive changes at post tDCS compared to baseline represent an improvement in the measure.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: FA | DMN FA | 0.000 score on a scale | Standard Deviation 0.007 |
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: FA | SN FA | 0.003 score on a scale | Standard Deviation 0.009 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: FA | SN FA | -0.002 score on a scale | Standard Deviation 0.011 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: FA | DMN FA | -0.003 score on a scale | Standard Deviation 0.006 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: FA | DMN FA | -0.002 score on a scale | Standard Deviation 0.008 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: FA | SN FA | -0.002 score on a scale | Standard Deviation 0.009 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: FA | DMN FA | 0.000 score on a scale | Standard Deviation 0.008 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: FA | SN FA | 0.001 score on a scale | Standard Deviation 0.011 |
Secondary
Change in Structural Connectivity: MD, AxD, RaD
Mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RaD) are assessed on diffusion weighted imaging. MD, AxD, RaD values are averaged in default mode network (DMN) and salience network (SN) regions of interest. MD, AxD, and RaD measure water diffusion and are expressed in mm\^2/s (starting from 0 with no maximum value; scaled at x10\^-3). Higher values denote higher diffusion and lower connectivity. Negative changes at post tDCS compared to baseline represent an improvement in the measure.
Time frame: Baseline, post tDCS (week 3)
Population: Modified intention-to-treat sample (participants completing intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | DMN MD | -0.003 x10^-3 mm^2/s | Standard Deviation 0.017 |
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | SN MD | -0.004 x10^-3 mm^2/s | Standard Deviation 0.016 |
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | DMN AxD | -0.004 x10^-3 mm^2/s | Standard Deviation 0.017 |
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | SN AxD | -0.004 x10^-3 mm^2/s | Standard Deviation 0.017 |
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | DMN RaD | -0.002 x10^-3 mm^2/s | Standard Deviation 0.017 |
| AD: Anodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | SN RaD | -0.005 x10^-3 mm^2/s | Standard Deviation 0.017 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | SN RaD | 0.000 x10^-3 mm^2/s | Standard Deviation 0.015 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | SN AxD | -0.008 x10^-3 mm^2/s | Standard Deviation 0.029 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | DMN MD | -0.001 x10^-3 mm^2/s | Standard Deviation 0.019 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | DMN AxD | -0.006 x10^-3 mm^2/s | Standard Deviation 0.024 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | SN MD | -0.002 x10^-3 mm^2/s | Standard Deviation 0.017 |
| AD: Cathodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | DMN RaD | 0.001 x10^-3 mm^2/s | Standard Deviation 0.017 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | SN MD | 0.010 x10^-3 mm^2/s | Standard Deviation 0.009 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | DMN AxD | 0.009 x10^-3 mm^2/s | Standard Deviation 0.014 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | SN AxD | 0.014 x10^-3 mm^2/s | Standard Deviation 0.018 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | SN RaD | 0.008 x10^-3 mm^2/s | Standard Deviation 0.009 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | DMN RaD | 0.007 x10^-3 mm^2/s | Standard Deviation 0.009 |
| bvFTD: Anodal tDCS of the SN | Change in Structural Connectivity: MD, AxD, RaD | DMN MD | 0.007 x10^-3 mm^2/s | Standard Deviation 0.008 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | DMN RaD | 0.006 x10^-3 mm^2/s | Standard Deviation 0.009 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | SN RaD | 0.005 x10^-3 mm^2/s | Standard Deviation 0.011 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | SN MD | 0.007 x10^-3 mm^2/s | Standard Deviation 0.008 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | SN AxD | 0.010 x10^-3 mm^2/s | Standard Deviation 0.012 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | DMN MD | 0.007 x10^-3 mm^2/s | Standard Deviation 0.008 |
| bvFTD: Cathodal tDCS of the DMN | Change in Structural Connectivity: MD, AxD, RaD | DMN AxD | 0.008 x10^-3 mm^2/s | Standard Deviation 0.011 |