Abstract
IntroductionPrediagnostic features of Parkinson's Disease are well described but prediagnostic Progressive Supranuclear Palsy (PSP) is less understood. The diagnosis of PSP is delayed by an average of three years after symptom onset. Understanding the changes that occur in the prediagnostic period will aid earlier diagnosis, clarify the natural history, and may aid the design of early disease-modifying therapy trials. We set out to identify motor and cognitive markers of prediagnostic PSP, with Parkinson's disease as a comparator condition, in a large prospective cohort. MethodsBaseline UK Biobank data from 502,504 individuals were collected between 2006 and 2010. Subsequent PSP and Parkinson's disease cases were identified from primary and secondary care electronic health records' diagnostic coding data and death registry, with 5404 matched controls. Results176 PSP cases (time to diagnosis 7.8 ± 2.8 years) and 2526 Parkinson's disease cases (time to diagnosis 7.8 ± 2.9 years) were identified. At baseline, those later diagnosed with PSP had slower reaction times, weaker hand grip, lower fluid intelligence, prospective memory, self-rated health scores and digit recall than controls. Reaction times were correlated with time to diagnosis. The PSP group had higher mortality than both Parkinson's disease and control groups. ConclusionsMotor slowing, cognitive dysfunction, and postural instability are clinical diagnostic features of PSP that are typically symptomatic three years before diagnosis. Objective markers of these features were evident on average 7.8 years before diagnosis. Our findings suggest the existence of a long prediagnostic phase in PSP, with subtle changes in motor and cognitive function.
Highlights
Prediagnostic features of Parkinson’s Disease are well described but prediagnostic Progressive Supranuclear Palsy (PSP) is less understood
An alternative opportunity to study the prediagnostic phase is using large scale, prospective cohort level data such as that found in the UK Biobank (UKB)
The principal results of this study are that people who will later receive a diagnosis of PSP differ in cognition and motor function several years before diagnosis, compared to age and sex-matched controls
Summary
Prediagnostic features of Parkinson’s Disease are well described but prediagnostic Progressive Supranuclear Palsy (PSP) is less understood. An alternative opportunity to study the prediagnostic phase is using large scale, prospective cohort level data such as that found in the UK Biobank (UKB) Such datasets offer a unique window into subtle changes during the prediagnostic phase of PSP with objective assessments often performed many years before a diagnosis is made. Drawing on concepts from other neurodegenerative disorders, we propose that the pre diagnostic period of PSP consists of (i) a presymptomatic phase, in which there are neuropathological changes present but without symptoms; and (ii) a symptomatic phase, in which neuropathological changes are Parkinsonism and Related Disorders 95 (2022) 59–64 sufficiently advanced to cause symptoms, which in turn may be pro dromal (including but not limited to symptoms “suggestive of” PSP [13]), or fully manifest (symptoms fulfilling diagnostic criteria) The latter are the basis of the eventual diagnosis
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