In this study, patients will receive their usual medical treatment for motor and non-motor symptoms from their

primary neurologist. The investigators will use a streamlined form of PD specific health education prepared by the VA: My Parkinson's Story, which consists of a series of short videos prepared by the VA PADRECCs addressing various aspects of PD. These 6-12 minutes long videos are freely available on YouTube. The investigators can also provide them on a CD if subjects desire. They start with a patient testimony about the topic of the episode, followed by comments of experts in the field. The title of the episodes are: Early Parkinson's, Medications, Exercise, Memory, Visual Disturbances, Depression, Sleep, Speech and Swallowing, Impulsive Behaviors, Driving, Pain, Dyskinesias, Deep Brain Stimulation, Advanced Parkinson's Disease, Falls, The Caregiver, Hospitalization, Genetics, Environmental Exposure, Atypical Parkinsonism

Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

Motor function. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Motor Experiences of Daily Living questionnaire (Part II). It measures motor function based on patient/caregiver responses. Each item is rated 0-4, and the score reflect the status of each item over the past week. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-52). Higher scores worse at individual datapoints. Lower change score better.

Measures change in the severity of parkinsonism while antiparkinsonian medications are working. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Motor section (Part III), measured in the ON state. It measures specific signs like rigidity, tremor, bradykinesia (slowness of movement), and gait abnormalities by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-132). Higher scores worse for individual data points. Lower value better for change score.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Motor Fluctuations and Dyskinesia questionnaire. It measures duration, severity, and functional impact of dyskinesias and OFF periods by questionnaire administered by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-24). Higher scores worse at data points. Lower change score better.

This is the simple addition of MDS-UPDRS Part I, II, and III (ON) total scores. This is a global measure of disease severity and encompasses motor and non-motor symptoms by subjective and objective measures. Higher scores at data points worse. Lower change scores better.

Motor function. Locomotion, endurance. Distance that a participant can walk in 2-minutes at their usual speed, a measure in NIH Toolbox Motor Battery. It is measured in the ON state. Higher data point and change score better.

An assessment of fine motor dexterity. Participants are asked to place 9 pegs into a board with 9 holes, then remove them as quickly as possible, one hand at a time. Time to complete is reported. Part of NIH Toolbox Motor Battery. measured in the "practically defined" OFF state (after overnight, ~12 hours, withdrawal of PD medications). Higher time to complete is worse for individual data points. Lower value better for change score.

An assessment of fine motor dexterity. Participants are asked to place 9 pegs into a board with 9 holes, then remove them as quickly as possible, one hand at a time. Time to complete is reported. Part of NIH Toolbox Motor Battery. measured in the ON state (when antiparkinsonian medications are working).

Higher time to complete is worse for individual data points. Lower value better for change score.

This is a brief cognitive screening test that measures various domains. Range 0-30. A score of 26 or over is considered to be normal. Higher score at data points and for change better.

Composite measure of cognitive impairment (COGSTAT) by assigning standard T scores (mean=50, SD=10) to each of the seven tests from the neuropsychological assessment battery (COWA, CFT-Copy, CFT-Recall, AVLT-Recall, BVRT, BLOCKS, and TMT [B-A]). Higher scores better.

Number of words created for each letter (C, F, L) of the Controlled Oral Word Association Test over 60 seconds for each letter. A test of verbal fluency, probes executive function (initiation, self-monitoring, inhibition of repeats), language (lexical access, phonemic organization), attention and working memory domains. Average healthy adult produces 12-15 words per letter. Higher score at data points and change score better.

Total score of the completion of the Block Design test. This test evaluates the ability to analyze and synthesize abstract visual patterns, manipulate spatial information mentally, and coordinate visual-motor construction skills. Raw score is sum of all points based on accuracy and speed of reproducing 14 designs. (range=0-68) - higher score and change score better.

Judgement of Line Orientation test measures ability to perceive and match the angular relationships between line orientations. It is a visuospatial perception test. Raw score is sum of all correctly identified items (range 0-30). Higher score at data points and change score better.

Cognition. Memory. Number of words that can be recalled after at least 30-minutes after hearing the list. Higher scores at data points and change scores better.

Ability to copy the Rey-Osterrieth Complex Figure. Measures visuospatial construction, perceptual organization, planning, and motor control. There are 18 distinct elements, each scored 0-2, with a range of total score 0-36. Higher score at data points and change score better.

Ability to remember and draw the Rey-Osterrieth Complex Figure as accurately as possible after 30 minutes of copying it. It measures long-term visual memory and retention. There are 18 distinct elements, each scored 0-2, with a range of total score 0-36. Higher score at data points and change score better.

Test of visuospatial perception and memory. 10 geometric designs are shown to the participant. Each design is viewed for 10 seconds and then reproduced from memory. We are reporting error counts (range 0-10). Higher scores worse at data points. Lower change value better.

Test of processing speed, visual scanning. Time in seconds to connect numbers in ascending order. Higher time at data points worse. Lower change value better.

Test of set-shifting, executive function, divided attention. Time to connect letters and numbers, alternating between numbers and letters, going in ascending order. Higher time worse. Lower change value better.

Measure of executive control from motor speed. Calculated as (Trail Making Test B - Trail Making Test A). Higher scores at data points worse. Lower change scores better.

Severity of depression. Higher scores worse. Range: 0-15

anxiety symptoms within the last week. 21-item self-report questionnaire each describing a common anxiety symptom (physical or cognitive). Item scores: 0 - Not at all, 1 - Mildly-it did not bother me much, 2 - Moderately-it was very unpleasant but I could bear it, 3 - Severely-I could barely stand it. Range 0-63. Higher scores worse at data points. Lower change value better.

Severity of fatigue. questions on symptoms of fatigue within the last week. Format: 9 statements such as "I am easily fatigued" rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree).

Total score = sum of all items / number of items answered (i.e., average of 9 items). Range: 1 - 7. Interpretation: 1-2=No or minimal fatigue, 3-4=Moderate fatigue, ≥ 5: Severe fatigue (commonly used clinical cutoff). Higher scores worse at data points. Lower change score better.

LEDD is a standardized measure used to compare the total dopaminergic medication load across different Parkinson's disease (PD) treatments. It converts various dopaminergic agents to a common reference - the amount equivalent to 100 mg of standard oral levodopa - allowing consistent comparison across studies and patients. Higher is worse at data points. Lower change value better.

Total of all reporting groups

sex

total number of years of school

The Hoehn and Yahr scale is a 5-stage ordinal rating system in Parkinson's disease. Stages: 0 - Asymptomatic, 1- Unilateral involvement only, 2 - Bilateral involvement without impairment of balance, 3 - Mild to moderate involvement; some postural instability but physically independent; needs assistance to recover from pull test, 4 - Severe disability; still able to walk or stand unassisted, 5 - Wheelchair bound or bedridden unless aided.

time since diagnosis

LEDD is a standardized measure used to compare the total dopaminergic medication load across different Parkinson's disease (PD) treatments. It converts various dopaminergic agents to a common reference - the amount equivalent to 100 mg of standard oral levodopa - allowing consistent comparison across studies and patients. Higher is worse.

Measurement of aerobic fitness in the ON stage. VO2 max is the maximum amount of oxygen the body can use during intense exercise, serving as a key indicator of cardiovascular fitness and endurance. It is measured in milliliters of oxygen per kilogram of body weight per minute (mL/kg/min). Higher is better.

Distance that a participant can walk in 2-minutes at their usual speed, a measure in NIH Toolbox Motor Battery. It is measured in the ON state. Higher is better.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Motor section (Part III), measured in the "practically defined" OFF state (after overnight, ~12 hours, withdrawal of PD medications). It measures specific signs like rigidity, tremor, bradykinesia (slowness of movement), and gait abnormalities by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-132). Higher scores worse.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Non-Motor Experiences of Daily Living questionnaire (Part I). Part IA It measures complex behaviors (e.g., cognition, mood) by the rater based on patient/caregiver responses. Part IB asks patient/caregiver about various body functions. Each item is rated 0-4, and the score reflect the status of each item over the past week. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score of IA and IB is reported (range 0-52). Higher scores worse.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Motor Experiences of Daily Living questionnaire (Part II). It measures motor function based on patient/caregiver responses. Each item is rated 0-4, and the score reflect the status of each item over the past week. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-52). Higher scores worse.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Motor section (Part III), measured in the ON state (when antiparkinsonian medications are working). It measures specific signs like rigidity, tremor, bradykinesia (slowness of movement), and gait abnormalities by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-132). Higher scores worse.

This is the simple addition of MDS-UPDRS Part I, II, and III (ON) total scores. This is a global measure of disease severity and encompasses motor and non-motor symptoms by subjective and objective measures. Higher scores worse.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Motor Fluctuations and Dyskinesia questionnaire. It measures duration, severity, and functional impact of dyskinesias and OFF periods by questionnaire administered by a certified rater.Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-24). Higher scores worse.

An assessment of fine motor dexterity. Participants are asked to place 9 pegs into a board with 9 holes, then remove them as quickly as possible, one hand at a time. Time to complete is reported. Part of NIH Toolbox Motor Battery. measured in the "practically defined" OFF state (after overnight, ~12 hours, withdrawal of PD medications). Higher time worse.

An assessment of fine motor dexterity. Participants are asked to place 9 pegs into a board with 9 holes, then remove them as quickly as possible, one hand at a time. Time to complete is reported. Part of NIH Toolbox Motor Battery. measured in the ON state (when antiparkinsonian medications are working). Higher time worse.

Uncorrected Standard Score of the NIH Toolbox Flanker Inhibitory Control and Attention Test. The Raw Score is based on number correct × average reaction time (accuracy & speed composite). The Uncorrected Standard Score is based on age-normed raw score with mean = 100 and SD = 15. Score range 40-160 with interpretation below:

≥ 130 - Very Superior, 115-129 - Superior, 85-114 - Average, 70-84 - Below Average, < 70 - Impaired / markedly low attention control. Higher score better.

Total score on the Montreal Cognitive Assessment. This is a brief cognitive screening test that measures various domains. Range 0-30. A score of 26 or over is considered to be normal. Higher score better.

Number of words created for each letter (C, F, L) of the Controlled Oral Word Association Test over 60 seconds for each letter. A test of verbal fluency, probes executive function (initiation, self-monitoring, inhibition of repeats), language (lexical access, phonemic organization), attention and working memory domains. Average healthy adult produces 12-15 words per letter. Higher score better.

Total score of the completion of the Block Design test. This test evaluates the ability to analyze and synthesize abstract visual patterns, manipulate spatial information mentally, and coordinate visual-motor construction skills. Raw score is sum of all points based on accuracy and speed of reproducing 14 designs (range=0-68). Higher score better.

Judgement of Line Orientation test measures ability to perceive and match the angular relationships between line orientations. It is a visuospatial perception test. Raw score is sum of all correctly identified items (range 0-30). Higher score better.

The number of words a person can recall from the AVLT after 30 minutes. Higher score better.

Ability to copy the Rey-Osterrieth Complex Figure. Measures visuospatial construction, perceptual organization, planning, and motor control. There are 18 distinct elements, each scored 0-2, with a range of total score 0-36. Higher score better.

Ability to remember and draw the Rey-Osterrieth Complex Figure as accurately as possible after 30 minutes of copying it. It measures long-term visual memory and retention. There are 18 distinct elements, each scored 0-2, with a range of total score 0-36. Higher score better.

Test of processing speed, visual scanning. time in seconds to connect numbers in ascending order. Higher time worse.

Test of set-shifting, executive function, divided attention. Time to connect letters and numbers, alternating between numbers and letters, going in ascending order. Higher time worse.

Number of safety errors made during an experimental real-world road drive test, scored by a certified driving instructor per criteria in the Iowa Department of Transportation's Drive Test Scoring Standards. Higher error count score worse.

questionnaire regarding activities of daily living and ability within the last month. PDQ-39 has 8 domains: Mobility (10 items) → max = 40, Activities of daily living (6 items) → max = 24, Emotional well-being (6 items) → max = 24, Stigma (4 items) → max = 16, Social support (3 items) → max = 12, Cognitions (4 items) → max = 16, Communication (3 items) → max = 12, Bodily discomfort (3 items) → max = 12. Domain Score=(Sum of item scores/Maximum possible)*100 . The main outcome measure is PDQ-39 Summary Index (PDQ-39 SI) is the mean of the 8 domain scores (range = 0 to 100). Higher score worse.

rating of mood within the last week, yes or no responses only to questions like "Do you often feel helpless?". 1 point for each depressive ("yes" or "no") answer, depending on item phrasing. Score Interpretation: 0-4 - Normal (no depression), 5-8 - Mild depression, 9-11 - Moderate depression, 12-15 - Severe depression. Score range: 0-15. Higher scores worse.

anxiety symptoms within the last week. 21-item self-report questionnaire each describing a common anxiety symptom (physical or cognitive). Item scores: 0 - Not at all, 1 - Mildly-it did not bother me much, 2 - Moderately-it was very unpleasant but I could bear it, 3 - Severely-I could barely stand it. Range 0-63. Higher scores worse.

questions on symptoms of fatigue within the last week. Higher scores worse. Format: 9 statements such as "I am easily fatigued" rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree).

Total score = sum of all items / number of items answered (i.e., average of 9 items). Range: 1 - 7. Interpretation: 1-2=No or minimal fatigue, 3-4=Moderate fatigue, ≥ 5: Severe fatigue (commonly used clinical cutoff).

diffusion coefficient of Radial Diffusivity on Diffusion Tensor Imaging (DTI). Higher scores worse.

diffusion coefficient of Radial Diffusivity on Diffusion Tensor Imaging (DTI). Higher scores worse.

diffusion coefficient of Radial Diffusivity on Diffusion Tensor Imaging (DTI). Higher scores worse.

Composite measure of cognitive impairment (COGSTAT) by assigning standard T scores (mean=50, SD=10) to each of the seven tests from the neuropsychological assessment battery (COWA, CFT-Copy, CFT-Recall, AVLT-Recall, BVRT, BLOCKS, and TMT [B-A]). Higher scores better.

test of visuospatial perception and memory. 10 geometric designs are shown to the participant. Each design is viewed for 10 seconds and then reproduced from memory. We are reporting error counts (range 0-10). Higher scores worse.

Measures change in the executive function domains of inhibitory control and attention. Uncorrected Standard Score of the NIH Toolbox Flanker Inhibitory Control and Attention Test. The Raw Score is based on number correct × average reaction time (accuracy & speed composite). The Uncorrected Standard Score is based on age-normed raw score with mean = 100 and SD = 15. Score range 40-160 with interpretation below:

≥ 130 - Very Superior, 115-129 - Superior, 85-114 - Average, 70-84 - Below Average, < 70 - Impaired / markedly low attention control. Higher scores better for individual data points. Higher value better for change score.

Number of safety errors made during an experimental real-world road drive test, scored by a certified driving instructor per criteria in the Iowa Department of Transportation's Drive Test Scoring Standards. Higher error count score worse. Lower scores better for change score.

Questionnaire regarding activities of daily living and ability within the last month. PDQ-39 has 8 domains: Mobility (10 items) → max = 40, Activities of daily living (6 items) → max = 24, Emotional well-being (6 items) → max = 24, Stigma (4 items) → max = 16, Social support (3 items) → max = 12, Cognitions (4 items) → max = 16, Communication (3 items) → max = 12, Bodily discomfort (3 items) → max = 12. Domain Score=(Sum of item scores/Maximum possible)*100 . The main outcome measure is PDQ-39 Summary Index (PDQ-39 SI) is the mean of the 8 domain scores (range = 0 to 100). Higher scores at datapoints are worse. Lower change score is better.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Non-Motor Experiences of Daily Living questionnaire (Part I). Part IA It measures complex behaviors (e.g., cognition, mood) by the rater based on patient/caregiver responses. Part IB asks patient/caregiver about various body functions. Each item is rated 0-4, and the score reflect the status of each item over the past week. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score of IA and IB is reported (range 0-52). Higher scores at data points worse. Lower change scores better.

Motor function. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Motor Experiences of Daily Living questionnaire (Part II). It measures motor function based on patient/caregiver responses. Each item is rated 0-4, and the score reflect the status of each item over the past week. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-52). Higher scores worse at individual datapoints. Lower change score better.

Measures change in the severity of parkinsonism while antiparkinsonian medications are working. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Motor section (Part III), measured in the ON state. It measures specific signs like rigidity, tremor, bradykinesia (slowness of movement), and gait abnormalities by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-132). Higher scores worse for individual data points. Lower value better for change score.

Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Motor Fluctuations and Dyskinesia questionnaire. It measures duration, severity, and functional impact of dyskinesias and OFF periods by questionnaire administered by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-24). Higher scores worse at data points. Lower change score better.

This is the simple addition of MDS-UPDRS Part I, II, and III (ON) total scores. This is a global measure of disease severity and encompasses motor and non-motor symptoms by subjective and objective measures. Higher scores at data points worse. Lower change scores better.

Motor function. Locomotion, endurance. Distance that a participant can walk in 2-minutes at their usual speed, a measure in NIH Toolbox Motor Battery. It is measured in the ON state. Higher data point and change score better.

An assessment of fine motor dexterity. Participants are asked to place 9 pegs into a board with 9 holes, then remove them as quickly as possible, one hand at a time. Time to complete is reported. Part of NIH Toolbox Motor Battery. measured in the "practically defined" OFF state (after overnight, ~12 hours, withdrawal of PD medications). Higher time to complete is worse for individual data points. Lower value better for change score.

An assessment of fine motor dexterity. Participants are asked to place 9 pegs into a board with 9 holes, then remove them as quickly as possible, one hand at a time. Time to complete is reported. Part of NIH Toolbox Motor Battery. measured in the ON state (when antiparkinsonian medications are working).

Higher time to complete is worse for individual data points. Lower value better for change score.

This is a brief cognitive screening test that measures various domains. Range 0-30. A score of 26 or over is considered to be normal. Higher score at data points and for change better.

Measurement of aerobic fitness in the ON stage. VO2 max is the maximum amount of oxygen the body can use during intense exercise, serving as a key indicator of cardiovascular fitness and endurance. It is measured in milliliters of oxygen per kilogram of body weight per minute (mL/kg/min). Higher scores at data points and change score better.

Composite measure of cognitive impairment (COGSTAT) by assigning standard T scores (mean=50, SD=10) to each of the seven tests from the neuropsychological assessment battery (COWA, CFT-Copy, CFT-Recall, AVLT-Recall, BVRT, BLOCKS, and TMT [B-A]). Higher scores better.

Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

DTI MRI was not available in all subjects.

Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

DTI MRI was not available in all completers.

Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

DTI not available in all completers

LEDD is a standardized measure used to compare the total dopaminergic medication load across different Parkinson's disease (PD) treatments. It converts various dopaminergic agents to a common reference - the amount equivalent to 100 mg of standard oral levodopa - allowing consistent comparison across studies and patients. Higher is worse at data points. Lower change value better.

Number of words created for each letter (C, F, L) of the Controlled Oral Word Association Test over 60 seconds for each letter. A test of verbal fluency, probes executive function (initiation, self-monitoring, inhibition of repeats), language (lexical access, phonemic organization), attention and working memory domains. Average healthy adult produces 12-15 words per letter. Higher score at data points and change score better.