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BackgroundA number of early features can precede the diagnosis of Parkinson's disease (PD).ObjectiveTo test an online, evidence‐based algorithm to identify risk indicators of PD in the UK population.MethodsParticipants aged 60 to 80 years without PD completed an online survey and keyboard‐tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine‐rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD (“intermediate markers”), including smell loss, rapid eye movement–sleep behavior disorder, and finger‐tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed.ResultsA total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow‐up (all P values < 0.001). Incident PD diagnoses during follow‐up were significantly associated with baseline risk score (hazard ratio = 4.39, P = .045). GBA variants or G2019S LRRK2 mutations were found in 47 participants, and the predictive power for incident PD was improved by the addition of genetic variants to risk scores.ConclusionsThe online PREDICT‐PD algorithm is a unique and simple method to identify indicators of PD risk. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Classical work in squid axon reports resting membrane potential is independent of temperature, but our findings suggest that this is not the case for axons in mammalian optic nerve. Refractory period duration changes over 10 times between 37 °C and room temperature, and afterpotential polarity is also acutely temperature sensitive, inconsistent with changes in temperature impacting nerve function only through altered rates of ion channel gating kinetics. Our evidence suggests that the membrane potential is enhanced by warming, an effect reduced by exposure to ouabain. The temperature dependence can be explained if axonal Na(+)/K(+) ATPase continuously expels Na(+) ions that enter axons largely electroneutrally, thereby adding a substantial electrogenic component to the membrane potential. Block of the Na(+) transporter NKCC1 with bumetanide increases refractoriness, like depolarization, indicating that this is a probable route by which Na(+) enters, raising the expectation that the rate of electroneutral Na(+) influx increases with temperature and suggesting a temperature-dependent transmembrane Na(+) cycle that contributes to membrane potential.

Introduction: There is an urgent need to identify robust biomarkers for Parkinson's disease (PD).