1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)

\[18F\]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower \[18F\]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because \[18F\]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative \[18F\]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the reference region to yield the Kocc measure of \[18F\]-FDOPA influx rate. Higher \[18F\]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity.

Time frame: Baseline (prior to LDOPA or placebo administration)

Population: Participants who had a baseline \[18F\]-FDOPA PET scan

The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of 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 is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of 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 is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Week 3 to Week 7 (post-Step 2)

Population: Participants with Week 3 and Week 7 data available were analyzed

In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

Subjects were 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. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

Subjects were 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. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Week 3 to Week 7 (post-Step 2)

Population: Participants with Week 3 and Week 7 data available were analyzed

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 reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

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 reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Week 3 to Week 7 (post-Step 2)

Population: Participants with Week 3 and Week 7 data available were analyzed

Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked 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 were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked 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 were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Week 3 to Week 7 (post-Step 2)

Population: Participants with Week 3 and Week 7 data available were analyzed

Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Week 4 to Week 7 (post-Step 2)

Population: Participants with Week 4 and Week 7 data available were analyzed

QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Baseline to 3 weeks (post Step 1)

Population: Participants with Baseline and Week 3 data available were analyzed

QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.

Time frame: Change from Week 4 to Week 7 (post-Step 2)