A Study of L-DOPA for Depression and Slowing in Older Adults

Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

Digit symbol substitution test (DSST) is a neuropsychological test sensitive to brain damage, dementia, age and depression. The test is not sensitive to the location of brain-damage (except for damage comprising part of the visual field). It consists of (e.g. nine) digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time (e.g. 90 or 120 sec) is measured. The higher the number, the better the score.

Digit symbol substitution test (DSST) is a neuropsychological test sensitive to brain damage, dementia, age and depression. The test is not sensitive to the location of brain-damage (except for damage comprising part of the visual field). It consists of (e.g. nine) digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time (e.g. 90 or 120 sec) is measured. The higher the number, the better the score.

This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflected the number of correct items (of a possible 130) completed in 90 s; items were designed to minimize the number of errors that were made.

This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflected the number of correct items (of a possible 130) completed in 90 s; items were designed to minimize the number of errors that were made.

Subjects will be asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. The higher the number, the better the score.

Subjects will be asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. The higher the number, the better the score.

Patients' gait will be assessed as walking speed in m/s on a 15' walking course. Patients are instructed to walk at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials will be completed, and gait speed will be based on the average of 2 trials.

Patients' gait will be assessed as walking speed in m/s on a 15' walking course. Patients are instructed to walk at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials will be completed, and gait speed will be based on the average of 2 trials.

For the Dual Task, patients are instructed to walk at their usual pace while simultaneously verbally listing as many animals as possible. In addition, a counting Dual Task will be used in which patients are instructed to walk at their usual pace while simultaneously performing serial subtractions by three starting at 100. Patients will start and end at a point 2 meters from the Gaitrite mat to eliminate acceleration and deceleration effects. Dual Task will be assessed two times with the average used in the analyses

For the Dual Task, patients are instructed to walk at their usual pace while simultaneously verbally listing as many animals as possible. In addition, a counting Dual Task will be used in which patients are instructed to walk at their usual pace while simultaneously performing serial subtractions by three starting at 100. Patients will start and end at a point 2 meters from the Gaitrite mat to eliminate acceleration and deceleration effects. Dual Task will be assessed two times with the average used in the analyse.

Rating scale for depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria that has been increasingly used in antidepressant studies due to its equivalent weightings for each item, understandable anchor points, and inclusion of all Diagnostic and Statistical Manual of Mental Disorders criteria. Patients will be asked to circle the one response to each item that best describes them for the past seven days. The answers range 0-84. The higher the score the greater the depressive symptoms.

Rating scale for depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria that has been increasingly used in antidepressant studies due to its equivalent weightings for each item, understandable anchor points, and inclusion of all Diagnostic and Statistical Manual of Mental Disorders criteria. Patients will be asked to circle the one response to each item that best describes them for the past seven days. The answers range 0-84. The higher the score the greater the depressive symptoms.

Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.

Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.

Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.

Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.

Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.

Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.