Award Title: Can cognitive tests differentiate Progressive Supranuclear Palsy from Parkinson's Disease?
Funder: Dunhill Medical Trust

Abstract: Progressive Supranuclear Palsy (PSP) or Steele-Richardson-Olszewski syndrome (Steele, Richardson, & Olszewski, 1964) is a degenerative neurological disease that typically affects patients in their sixties and affects between one and five in every 100000 people (Nath et al., 2001). Current diagnostic practice follows the guidelines proposed by Höglinger et al., (2017) which considers paralysis of the eyes, postural instability and akinesia as key diagnostic indicators. However, there is no definitive test for PSP and PSP is often misdiagnosed as Parkinson Disease (Litvan et al., 1996; Willams & Lees 2010). This is highly problematic, because the underlying pathology of PSP is very different to that of PD. Specifically, PSP is unresponsive to dopaminergic medications such as Levodopa (Hajjar & Cooper, 2016), but many patients are prescribed them because PSP is mistaken for PD. Common side effects of these medications include nausea, loss of appetite, constipation, hypotension, headaches & insomnia.  The inability to make accurate, early diagnosis of PSP is distressing for the patient carers, exposes patients to medications whose side-effects reduce quality of life and limits the capacity to make adequate care plans.  Previous research indicates that patients with PSP may have problems with attention, memory and recognizing emotions (Burrell et al., 2014, Smith & Archibald 2018a,b) that reduces their quality of life (Schragg et al., 2003). These cognitive problems are consistent with theoretical models which propose a tight coupling between the eye-movement system and mental processes such as attention, memory (e.g. Smith & Schenk, 2012; Awh et al., 2006) and emotion recognition (Atkinson & Smithson 2013). Indeed, a handful of small studies have indicated that PSP patients are significantly worse than PD patients at tests of visuospatial attention (Kimmura et al., 1980, Rafal et al., 1988). However, overall the cognitive problems associated with PSP are not well understood, despite being identified as having considerable potential for diagnosis (Burrell et al., 2014). The goal of this project is to test the idea that cognitive tests of visuospatial attention, memory and emotional processing can be used to reliably retrospectively classify individual patients as having PSP or PD. Patients with PSD, PD and controls will complete a battery of computerised tests of attention, memory and emotion recognition in their own homes. Linear discriminant analysis will be applied to establish which tests most accurately classify patients.  The results will inform our long-term goal of developing a cheap and effective tool for early diagnosis of PSP.

Lay Abstract: Progressive Supranuclear Palsy (PSP) is a rare brain disease that typically begins to affect people during their sixties and causes problems with walking, swallowing, speech and eye-movements. Unfortunately, because it is a rare disease doctors often mistakenly diagnose PSP as Parkinson’s disease (PD). Misdiagnosis of this disease is a problem for many reasons. Firstly, the medicines that are effective for treating PD  do not work for PSP. They also have unpleasant side effects such as nausea and vomiting, changes to blood pressure, loss of appetite, constipation, hallucinations, headaches & insomnia. Misdiagnosis therefore is both harmful to the patient and wasteful of scarce NHS resources. Secondly, the prognosis for PSP is much worse than that of PD and the disease progresses much more swiftly, so misdiagnosis makes it a lot harder for patients and carers to gain access to the financial support needed to adjust their lifestyle to maximise their quality of life. For example, patients with PSP often require home adaptations and wheelchairs to compensate for their reduced mobility. Finally, inaccurate diagnosis is distressing to patients and carers and leads to unnecessary hospital visits. It is therefore important to develop new ways to effectively diagnose PSP.  Existing research, including a pilot study we recently conducted, suggests that people with PSP have particular problems with attention, short term memory and the ability recognize facial emotions which are not experienced by people with Parkinson's disease. These cognitive problems may offer a new and cost-effective way of diagnosing PSP, but the current evidence relies on small studies. We therefore need to conduct a larger study to confirm that cognitive tests reliably differentiate between PSP and PD. We will ask patients to complete a set of computer based tests that measure visual attention, short term memory and their ability to recognize emotions. We will also measure their eye-movements. These tests can be completed using a laptop and a portable eye-tracker, so we can test people in their own homes to make it easier for them to participate. Our goal is to show  the scores on these tests can be used to classify individual  patients as having either PSP or PD. This research is an essential stepping-stone towards developing an accurate and accessible diagnostic test for PSP.

Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: NEUROLOGICAL