Open Label Study for the Use of Transcranial Ultrasound for Treatment of Age-Related Frailty

The SPPB is a series of tests used to evaluate lower extremity function and mobility in older people. The test consists of three major components, each of which are scored independently: 3 static balance tests, gait speed, and five timed sit-to-stand tests. Points are assigned based on performance, with a maximum possible score of 12 points. Higher scores are indicative of better functioning. A score of 0 on any item indicates lack of ability or functioning. The minimum clinically important difference for the total SPPB score is 1 point.

The SPPB is a series of tests used to evaluate lower extremity function and mobility in older people. The test consists of three major components, each of which are scored independently: 3 static balance tests, gait speed, and five timed sit-to-stand tests. Points are assigned based on performance, with a maximum possible score of 12 points. Higher scores are indicative of better functioning. A score of 0 on any item indicates lack of ability or functioning. The minimum clinically important difference for the total SPPB score is 1 point.

The MFI is a 20-item scale designed to evaluate five dimensions of fatigue: general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. Respondents use a scale ranging from 1 to 7 to indicate how aptly certain statements regarding fatigue represent their experiences. Several positively phrased items are reverse- scored. Higher total scores correspond with more acute levels of fatigue. Responses for the Multidimensional Fatigue Inventory will be defined as clinically significant when there is a 2-point difference.

The MFI is a 20-item scale designed to evaluate five dimensions of fatigue: general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. Respondents use a scale ranging from 1 to 7 to indicate how aptly certain statements regarding fatigue represent their experiences. Several positively phrased items are reverse- scored. Higher total scores correspond with more acute levels of fatigue. Responses for the Multidimensional Fatigue Inventory will be defined as clinically significant when there is a 2-point difference.

The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.

The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.

The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.

The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.

The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.

The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.

This self-report questionnaire assesses weekly frequency and duration of a variety of lifestyle physical activities that are meaningful and appropriate for older adults. It includes activities of various intensities (from light to vigorous) such as walking, running, hiking, swimming, bicycling, dancing, tennis, aerobics, yoga/tai chi, gardening, and housework. Intensity is reflected in the item stem (e.g., light and heavy gardening are separate items). The questionnaire is self-administered, although it can be interviewer administered. It is formatted to accommodate increasing visual problems with age by using a large font, adequate space on the page, and high contrast. A total caloric expenditure is calculated based on reported participant activity. Responses for the CHAMPS questionnaire will be defined as clinically significant when there is a 8 kcal/kg/week difference.

This self-report questionnaire assesses weekly frequency and duration of a variety of lifestyle physical activities that are meaningful and appropriate for older adults. It includes activities of various intensities (from light to vigorous) such as walking, running, hiking, swimming, bicycling, dancing, tennis, aerobics, yoga/tai chi, gardening, and housework. Intensity is reflected in the item stem (e.g., light and heavy gardening are separate items). The questionnaire is self-administered, although it can be interviewer administered. It is formatted to accommodate increasing visual problems with age by using a large font, adequate space on the page, and high contrast. A total caloric expenditure is calculated based on reported participant activity. Responses for the CHAMPS questionnaire will be defined as clinically significant when there is a 8 kcal/kg/week difference.

Participants will be asked to demonstrate grip strength in standard fashion for clinical evaluation. Using the JAMAR Technologies Hydraulic Hand Dynamometer, participants will squeeze the instrument with their dominant hand and generate a reading of grip strength in the output reading (units = kg). The MCID of the grip strength test is a change of at least 5.0 kg.

Participants will be asked to demonstrate grip strength in standard fashion for clinical evaluation. Using the JAMAR Technologies Hydraulic Hand Dynamometer, participants will squeeze the instrument with their dominant hand and generate a reading of grip strength in the output reading (units = kg). The MCID of the grip strength test is a change of at least 5.0 kg.

The GRC consists of a single likert-scale ranging from "-5" (very much worse) to "0" (neutral/no change) to "5" (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.