Rate of decline in progressive supranuclear palsy

The rate of patients' decline is critical to properly design trials of disease-modifying agents. We prospectively quantified the progression of 27 progressive supranuclear palsy (PSP) patients for at least 1 year to determine the rate of decline of motor, ocular-motor, neuropsychological, and neuropsychiatric features. PSP patients meeting the National Institute of Neurological Disorders and the Society for Progressive Supranuclear Palsy criteria were assessed using the PSP Rating Scale (PSP-RS) and modified UPDRS. The Mini-Mental State Examination (MMSE) and Frontal Assessment Battery assessed cognitive decline, the Neuropsychiatric Inventory assessed behavior, and the modified Schwab and England scale and UPDRS ADL assessed activities of daily living (ADL). The rate of change of each score was calculated as 1-year worsening score. Power and sample sizes were estimated. PSP patients showed a significant yearly decline in total and subtotal scores of the PSP-RS and UPDRS, as well as in MMSE, and UPDRS and Schwab and England ADL scores. In addition, they had significant deterioration of individual item scores reflecting major aspects of the disease (i.e., ocular-motor). The rate of decline reflected in the UPDRS mirrored that of the PSP-RS. The worsening of the ADL score was positively correlated with the PSP-RS progression of falls and ocular-motor subitem scores and with executive dysfunction. PSP patients showed a significant yearly decline in motor, ocular-motor, and ADL functions. Our findings suggest that using more-advanced technology to measure ocular-motor, postural instability, and ADL will be helpful in planning future therapeutic trials.