Leveraging Long-Term Smartwatch Data to Inform Parkinson’s Disease Progression, Subtypes, and Risk

Use of digital sensors to passively collect long-term, longitudinal data offers a step change in our ability to monitor Parkinson’s disease (PD). However, to date the evaluation of long-term digital sensor data has been neglected in favour of evaluating short-term data collected in controlled settings. To address this, we combined longitudinal clinical and biological assessment data from the Parkinson’s Progression Marker Initiative (PPMI) cohort with long-term (mean: 485 days) at-home digital monitoring data collected with the Verily Study Watch. We then derived digital timeseries components leveraging the long-term monitoring of the PPMI. We found three key findings: Firstly, that these digital timeseries components correlated with the rate of progression of motor (r = 0.23, p-value = 8.5×10-3, r = 0.26, p-value = 2.2×10-3) and autonomic symptoms (r = −0.23, p-value = 8.2×10-3), impairments in daily living (r = 0.26, p-value = 2.5×10-3), increase in medication requirements and complications (r = −0.25, p-value = 4.2×10-3), and rate of increase in cerebrospinal fluid (CSF) tau (ptau: r = 0.28, p-value = 2.6×10-3; ttau: r = 0.34, p-value = 1.2×10-4). Second, we derived digitally informed subtypes of PD and found higher similarity with CSF (0.35) and DaTscan (0.35) subtypes than has been found for previously published subtypes (CSF: 0.31±0.01, DaTscan: 0.31±0.02). Finally, we showed that long-term digital monitoring can inform PD risk and sensitively detect individuals with probable prodromal PD. Our findings highlight the wealth of application areas for digital sensors in PD research. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement PPMI (a public-private partnership) is funded by the Michael J. Fox Foundation for Parkinson's Research with funding partners including Abbvie, Acure, Allergan, Amathus, Avid, Biogen, Bial Biotech, Biolegend, Bristol‐Myers Squibb, Calico, Celgene, Covance, Dacapo brain-science, Jenali, 4D Pharma plc, GE Healthcare, Edmond J. Safra philanthropic foundation, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocine, Pfizer, Piramal, Prevail, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily and Voyager therapeutics. A.-K.S. and C.S. are funded by the Moondance Foundation as part of the Moondance Dementia Research Laboratory. A.-K.S. is supported by a PhD studentship funded by the Welsh Government through Health and Care Research Wales (HS-20-11). C.S. and V.E.-P. are supported by the UK Dementia Research Institute funded by the Medical Research Council (MRC), Alzheimer's Society and Alzheimer's Research UK. C.S. received funding from the Ser Cymru II programme (CU187) which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government. K.P. is funded by an MRC Clinician-Scientist Fellowship (MR/P008593/1) and a Transition Support Award (MR/V036084/1). V.E.-P. is funded by Joint Programming for Neurodegeneration (MRC: MR/T04604X/1), and Dementia Platforms UK (MRC: MR/L023784/2). N.H. has nothing to declare. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in the present study are available online under .