Longitudinal changes of early motor and cognitive symptoms in progressive supranuclear palsy: the OxQUIP study

Abstract

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative condition characterised by a range of motor and cognitive symptoms. Very little is known about the longitudinal change in these symptoms over time. Moreover, the effectiveness of clinical scales to detect early changes in PSP is still a matter of debate.

Objective: We aimed to determine longitudinal changes in PSP features using multiple closely spaced follow-up time points over a period of 2 years. Methods 28 healthy control and 28 PSP participants, with average time since onset of symptoms of 1.9 years, were prospectively studied every 3 months for up to 24 months. Changes from baseline scores were calculated at each follow-up time point using multiple clinical scales to identify longitudinal progression of motor and cognitive symptoms.

Results: The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, detected cognitive decline at baseline. Both scales revealed poor longitudinal sensitivity to clinical change in global cognitive symptoms. Conversely, the Movement Disorders Society Unified Parkinson's disease Rating Scale - part III and the PSP Rating Scale (PSPRS) reliably detected motor decline less than 2 years after disease onset. The 'Gait/Midline' PSPRS subscore consistently declined over time, with the earliest change being observed 6 months after baseline assessment.

Conclusion: While better cognitive screening tools are still needed to monitor cognitive decline in PSP, motor decline is consistently captured by clinical rating scales. These results support the inclusion of multiple follow-up time points in longitudinal studies in the early stages of PSP.

Keywords: clinical neurology; motor control.

Figure 1

Flow chart illustrating the inclusion and lost to follow-up of participants at each visit time point. Twenty-eight cases with progressive supranuclear palsy were recruited in 2016–2020. Participants completed a baseline assessment at visit one and underwent a follow-up assessment every 3 months over a period of 18 months. Of the 28 participants enrolled in the OxQUIP study, 15 withdrew due to a combination of reasons including: being too unwell to attend visits (9), death (5) or to a change of diagnosis (1). Participants reported as early clinical PSP-related symptoms prior to the first OXQUIP visit the following symptoms: speech impairments, falls, rigidity, problems with balance, hand tremors, pain, photosensitivity and micrographia. The figure also shows previous diagnosis received by the participants prior to the PSP diagnosis. PSP, progressive supranuclear palsy; PD, Parkinson’s disease; OxQUIP, Oxford Quantification in Parkinsonism.

Figure 2

Mean scores at each visit (A, B) and mean changes from baseline (C, D) in MDS-UPDRS-III and PSPRS total scores. Mean changes from baseline in PSPRS subscores (E–J). To determine the mean change in scores from baseline, ∆ values were calculated for each participant and scores were averaged for each visit. Figure shows values significant at level *p<0.05 and **p<0.008, the latter including adjustment for multiple comparisons with a Bonferroni correction. PSPRS, Progressive Supranuclear Palsy Rating Scale; MDS-UPDRS-III, Movement Disorders Society Unified Parkinson’s disease Rating Scale part III.

Figure 3

Velocity of progression of the enduring changes in total scores of PSPRS (A), MDS-UPDRS-III (B) and PSPRS ‘Gait/Midline’ subscore (C). Figure D shows a comparison between the velocity of progression of the enduring changes in scores represented in figures A–C. N=number of participants at each visit. MDS-UPDRS-III, Movement Disorders Society Unified Parkinson’s disease Rating Scale part III.; PSPRS, Progressive Supranuclear Palsy Rating Scale