Facilitating Diagnostics and Prognostics of Parkinsonian Syndromes Using Neuroimaging

Imaging biomarker of progression rate

The imaging biomarker consists of a machine learning model that distinguishes fast and slow progressors using the neuroimaging data. The performance of the model will be assessed quantitatively using widely adopted performance metrics: sensitivity, specificity, and accuracy.

Imaging biomarker that discriminates different neurodegenerative diseases

The imaging biomarker consists of a machine learning model that differentiates the parkinsonian diseases: PD, PSP, and MSA using the neuroimaging data. The performance of the model will be assessed quantitatively using widely adopted performance metrics from the classification confusion matrix. The metrics will include disease sensitivity, disease specificity, and disease specific accuracy and overall accuracy.

Change from baseline in MDS-UPDRS score

The Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the standard measure of PD severity used in multiple trials. This consists of four sub scales, Part I: non-motor experiences of daily living (13 items), Part ll: motor experiences of daily living (13 items), Part III: motor examination (18 items), and Part IV: motor complications (six items). Each subscale has a five-point scale ranging from 0-4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total score is the sum of the subscale scores for all four parts and ranges from 0 (no disability) to 200 (total dependence). Negative change from baseline scores indicate improvement.

Change from baseline in Unified Multiple System Atrophy Rating Scale (UMSARS) score

The Unified Multiple System Atrophy Rating Scale (UMSARS) is the standard scale for measuring disease severity in MSA. This scale is composed of 2 sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement.

Change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) score

The Progressive Supranuclear Palsy Rating Scale (PSPRS) is the standard scale used to quantitate severity in PSP. This is a quantitative measure of disability in participants with PSP. The PSPRS comprises 28 items in 6 areas. The available total score ranges from 0 (normal) to 100. Six items are rated on a 3-point scale (0-2) and 22 are rated on a 5-point scale (0-4). The History/Daily Activities area includes 7 items with ta total maximum of 24 points, the mentation area 4 items with 16 points, the bulbar area 2 items with 8 points, the ocular motor area 4 items with 16 points, the limb motor area 6 items with 16 points, and the gait area 5 items with 20 points. Negative change from baseline scores indicate improvement.

Change from baseline in Parkinson disease questionnaire

The Parkinson's Disease Questionnaire (PDQ-39) assesses to what degree PD subjects experience difficulties across 8 dimensions of daily living. The 39-question PDQ provides scores (expressed as a percentage) for each of the 8 scales: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. individual items are rated on a 5-point scale (0-4). Higher percentages represent worse quality of life, and a reduction in score over time represents improvement.