Non-invasive Stimulation of Brain Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.