This interesting study of “prediagnostic” progressive supranuclear palsy (PSP) out of the UK Biobank was recently published.  It concludes that symptoms of PSP can be seen almost 8 years before diagnosis.  Reaction time was the strongest predictive marker with changes evident as early as 10 years before diagnosis!
Note that no pathological confirmation of those with PSP was done for this study.

Here’s the introduction to the paper:

“Prediagnostic 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.”

And the conclusion:

“Motor 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.”

More specifically, people later diagnosed with PSP “differ in cognition and motor function several years before diagnosis, compared to age and sex-matched controls. They manifest differences in reaction time, hand grip strength, fluid intelligence, prospective memory, self-rated health score and digit recall tasks, and a tendency to falls.”

“Almost a third of the PSP cohort were initially diagnosed with Parkinson’s disease, indicating that a high degree of initial diagnostic uncertainty or error exists. As a group, prediagnostic PSP patients had more falls in the year prior to baseline assessment than both prediagnostic Parkinson’s disease patients and age and gender-matched controls, but falls were only reported by a minority (29/176, 16%). Reaction time was the strongest predictive marker with changes evident as early as 10 years before diagnosis and worsening closer to diagnosis.”

You can read the abstract (no charge) on the PubMed website here

Prediagnostic Progressive Supranuclear Palsy – Insights from the UK Biobank.
Street D, Whiteside D, Rittman T, Rowe JB.
Parkinsonism Relat Disord. 2022 Jan 11;95:59-64