Noninvasive Brain Stimulation for Mild Cognitive Impairment

The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words.

There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.

The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of 16 semantically related words and remember the list after a delay interval. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order.

A measure of semantic clustering is calculated by a computer program. It is a measure of the participant's tendency to recall words in semantically organized clusters (e.g. the participant recalled "apple" and "orange" even though the two fruit words were not presented sequentially). The computer algorithm includes words recalled on Trials 1-5 and adjusts for the possibility that a semantic cluster occurred by chance. The range of CVLT-II Semantic Clustering Scores is -3 to 9. Higher values represent a better outcome.

The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words.

After 5 learning trials and a subsequent 20-minute delay filled with unrelated tests, the participant was asked to recall the 16-word target list of the CVLT-II again. The total number of words correctly recalled was computed (range = 0 to 16). Higher values represent a better outcome.

The 15-item Geriatric Depression Scale (GDS) was also used as an outcome measure. Five of the GDS items are oriented toward the absence of depressive symptoms (e.g., Do you feel full of energy?) and 10 are oriented toward current depressive symptoms (e.g., Do you often feel helpless?). The participant is asked to answer "yes" or "no" on the basis of how they have been feeling over the past week.

The GDS total score ranges from 0 to 15. Lower values represent a better outcome.

The Everyday Cognition (ECog) questionnaire is comprised of 39 items about the ability to perform everyday tasks. Each item relates to memory, language, visual-spatial, or executive function. Each item is rated on a scale from 1 to 4 (1 = better or no change…4 = consistently much worse compared to 10 years ago).

For the Participant version of the ECog, the participant is asked to "Please rate your ability to perform certain everyday tasks now, as compared to your ability to do these same tasks 10 years ago." Total score range: 39-156. Higher values represent a worse outcome. The outcome score was adjusted for baseline.

The Everyday Cognition (ECog) questionnaire is comprised of 39 items about the ability to perform everyday tasks. Each item relates to memory, language, visual-spatial, or executive function. Each item is rated on a scale from 1 to 4 (1 = better or no change…4 = consistently much worse compared to 10 years ago).

For the Informant version of the ECog, the participant's study partner was asked to "Please rate the participant's ability to perform certain everyday tasks NOW, as compared to his/her ability to do these same tasks 10 years ago." Total score range: 39-156. Higher values represent a worse outcome. The outcome score was adjusted for baseline.

Functional Assessment Questionnaire, completed by the study partner at end of treatment (1 week after intervention, adjusted for baseline). Each 10 item is rated on a scale from 0 to 3 (0 = Normal; 1 = Has difficulty, but does by self; 2 = Requires assistance; 3 = Dependent.

Total score range: 0-30 (sum of 10 items). Interpretation: A total score of 9 (dependent in 3 or more activities) is the recommended cut-point for an indication of impaired function.

Higher values represent a worse outcome.

The Montreal Cognitive Assessment (MoCA) is a brief measure of global cognitive function. The total score has a range of 0 to 30; higher values represent a better outcome.

Brief Visuospatial Memory Test-Revised (BVMT-R) Trials 1-3 total recall raw score at end of treatment (1 week after intervention, adjusted for baseline); range: 0-36; higher values represent a better outcome

Category Fluency is a measure of verbal fluency in which the participant is asked to generate different exemplars from a semantic category specified by the examiner. For example, if the examiner says, 'articles of clothing,' correct responses include exemplars such as, 'shirt,' 'tie,' or 'hat.' The participant is given one minute to say all the responses they can think of. The values reported reflect the total number of correct, unique responses produced. Higher values represent a better outcome.

The Boston Naming Test (BNT) assesses the ability to verbally name pictured objects. The subject is shown a series of line drawings and asked to name the object. The test items become progressively more difficult. (The 42 items are presented in order of decreasing frequency of the target word). The total number of correct responses can range from 0 to 42. Higher values represent a better outcome.

Rey-Osterrieth Complex Figure (ROCF) Copy score at end of treatment (1 week after intervention, adjusted for baseline); range: 0-36; higher values represent a better outcome

In the Trail Making Part B test, the response form has a series of 25 circles; each circle contains a number or a letter. The participant is asked to connect the circles in order by alternating between the numbers and letters. The maximum time allowed is 300 seconds. Trails B is thought to require executive skills as well as processing speed. The Trail Making B seconds-to-complete scores were log transformed because the distribution of scores was positively skewed. We also reverse scored the log scores so that higher values would indicate a better outcome. To reverse the log scores, we used the formula:

reverse score = max(x) + 1 - x, where max(x) is the natural log of 300 or 5.70378.

For example, if a participant's time-to-complete score was 74 seconds, the natural log transformed score was 4.304. Reverse scoring yields a value of 2.4 (2.4 = 5.70378 + 1 - 4.304). The reverse-scaled, log transformed seconds-to-complete scores were used in all statistical analyses.

Attentional Network Task(ANT) correct reaction time, as measured by the ANT computerized test

Change from Baseline in Functional connectivity metrics (derived from the pre- and the post-intervention functional magnetic resonance imaging (fMRI) scans rs-fMRI scans) will be computed with respect to: connectivity within the Default Mode Network (DMN), and connectivity between the DMN and the Central Executive Network (CEN).

Brain-derived Neurotrophic Factor (BDNF) plasma levels were measured from blood samples that were collected during the first session and the last session of TMS intervention, after a minimum of 4 hours of fasting.

Higher change scores represent a better outcome.