A Longitudinal Study of Motor, Oculomotor and Cognitive Function in Progressive Supranuclear Palsy

Abstract

ObjectiveWe studied the annual change in measures of motor, oculomotor and cognitive function in progressive supranuclear palsy. This had twin objectives, to assess the potential for clinical parameters to monitor disease progression in clinical trials and to illuminate the progression of pathophysiology.MethodsTwenty three patients with progressive supranuclear palsy (Richardson’s syndrome) were compared to 22 matched controls at baseline and 16 of these patients compared at baseline and one year using: the progressive supranuclear palsy rating scale; the unified Parkinson’s disease rating scale; the revised Addenbrooke’s cognitive examination; the frontal assessment battery; the cubes section of the visual object and space perception battery; the Hayling and Brixton executive tests; and saccadic latencies.ResultsPatients were significantly impaired in all domains at baseline. However, cognitive performance was maintained over a year on the majority of tests. The unified Parkinson’s disease rating scale, saccadic latency and progressive supranuclear palsy rating scale deteriorated over a year, with the latter showing the largest change. Power estimates indicate that using the progressive supranuclear palsy rating scale as an outcome measure in a clinical trial would require 45 patients per arm, to identify a 50% reduction in rate of decline with 80% power.ConclusionsMotor, oculomotor and cognitive domains deteriorate at different rates in progressive supranuclear palsy. This may be due to differential degeneration of their respective cortical-subcortical circuits, and has major implications for the selection of outcome measures in clinical trials due to wide variation in sensitivity to annual rates of decline.

Managing cognition in progressive supranuclear palsy

“…This hypothesis is consistent with the finding that cholinesterase inhibitors are not effective in PSP [27]. The domain of visuospatial function is often impaired in people with PSP [24,26], though may be overlooked in the context of other more striking changes.…”

“…This may manifest as difficulty with planning and organization and can be readily assessed at the bedside using tests such as the frontal assessment battery [22], verbal fluency [23] or neuropsychological tests such as Trail Making Test B or Brixton spatial anticipation test [24]. Slowness of cognitive processes, including slow speed of processing, is characteristic of PSP, and has been termed bradyphrenia.…”

“…The striking deficit of letter fluency can aid the distinction of PSP from idiopathic PD; we have shown that patients who produced fewer than seven p-words in a minute were much more likely to have the syndrome of PSP rather than PD with a positive predictive value of this simple test alone of 0.81 and a negative predictive value of 0.93 [25]. Using the Frontal Assessment Battery and other tests of frontal lobe function, cognitive impairment is readily detectable at diagnosis but changes little over 12 months [24]. These findings suggest that frontal cognitive impairments are well established early in the disease process.…”

Mild Cognitive Impairment and Progression to Dementia in Progressive Supranuclear Palsy

“…Our findings confirmed and extended previous cross-sectional studies claiming the presence of cognitive impairment, prominently in the executive domain, in most PSP patients [4,6,14,15,16,17,18]. The present study showed that the number of PSP patients with dementia dramatically increased over time, involving more than 80% of PSP patients after 3 years.…”

“…The retrospective nature of data collection did not allow the evaluation of PSP-RS [15,19] or advanced clinical [18,20], imaging [21,22], and biological markers [23] in predicting dementia over time. Furthermore, cognition and motor dysfunction are strongly related, and several neuropsychological tests might be impaired because of motor dysfunction.…”