A Remote Longitudinal Observational Study of Individuals at Genetic Risk for Parkinson Disease

Abstract

Background and ObjectivesTo recruit and characterize a national cohort of individuals who have a genetic variant (LRRK2 G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials.MethodsIn partnership with 23andMe, Inc., a personal genetics company, LRRK2 G2019S carriers with and without PD were recruited to participate in an ongoing 36-month decentralized, remote natural history study. We examined concordance between self-reported and clinician-determined PD diagnosis. We applied the Movement Disorder Society Prodromal Parkinson's Disease Criteria and asked investigators to identify concern for parkinsonism to distinguish participants with probable prodromal PD. We compared baseline characteristics of LRRK2 G2019S carriers with PD, with prodromal PD, and without PD.ResultsOver 15 months, we enrolled 277 LRRK2 G2019S carriers from 34 states. At baseline, 60 had self-reported PD (mean [SD] age 67.8 years [8.4], 98% White, 52% female, 80% Ashkenazi Jewish, and 67% with a family history of PD), and 217 did not (mean [SD] age 53.7 years [15.1], 95% White, 59% female, 73% Ashkenazi Jewish, and 57% with a family history of PD). Agreement between self-reported and clinician-determined PD status was excellent (κ = 0.94, 95% confidence interval 0.89–0.99). Twenty-four participants had prodromal PD; 9 met criteria for probable prodromal PD and investigators identified concern for parkinsonism in 20 cases. Compared with those without prodromal PD, participants with prodromal PD were older (63.9 years [9.0] vs 51.9 years [15.1], p < 0.001), had higher modified Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor scores (5.7 [4.3] vs 0.8 [2.1], p < 0.001), and had higher Scale for Outcomes in PD for Autonomic Symptoms scores (11.5 [6.2] vs 6.9 [5.7], p = 0.002). Two-thirds of participants enrolled were new to research, 97% were satisfied with the overall study, and 94% of those without PD would participate in future preventive clinical trials.DiscussionAn entirely remote national cohort of LRRK2 G2019S carriers was recruited from a single site. This study will prospectively characterize a large LRRK2 G2019S cohort, refine a new model of clinical research, and engage new research participants willing to participate in future therapeutic trials.

Best Practices and Recommendations for Research Using Virtual Real-Time Data Collection: Protocol for Virtual Data Collection Studies

“…Results from the protocol review will be summarized under the themes of: (1) “modality of data collection,” (2) “equipment for data collection,” (3) “guided visit instruction or materials,” (4) “participant-staff interaction,” and (5) “reliability and validity of measures” (see Multimedia Appendix 2 [ 8 - 10 , 17 , 21 - 24 , 27 - 29 , 32 ]). Results and best practice recommendations from the current protocol review will be used in the design and implementation of a substudy to provide more evidence for virtual real-time data collection.…”

“…For example, multiple studies explained that providing hotspots was particularly effective in reducing barriers to participation, especially for racially or ethnically diverse and low-income populations [ 5 , 6 , 14 , 26 ]. Other studies that did not provide hotspots cited a lack of internet as an exclusion factor as well as a study limitation [ 11 , 15 , 21 , 23 , 24 , 28 ]. Studies that excluded participants without access to the internet limited the generalizability of their study population.…”

“…For example, multiple research teams collected anthropometric data (eg, height, weight, and waist circumference) remotely through real-time videos [ 5 , 6 , 9 - 28 ], while others collected anthropometric data by using recorded videos, telephone instructions, and multiple modes of instruction to assure data quality. Clinical research studies researching long-term illnesses and diagnoses (ie, Parkinson disease, Huntington disease, autism spectrum disorder, HIV, etc) used telehealth and videoconferencing during the COVID-19 pandemic [ 11 - 13 , 20 , 24 , 25 , 29 ]. Additionally, studies collected biospecimen samples or anthropometric data, whereas other studies administered fitness tests or surveys.…”

Genetic analysis and natural history of Parkinson’s disease due to the LRRK2 G2019S variant

“… 1 , 9 Precise phenoconversion rates have not been established. 10 Validating sensitive and specific prodromal criteria to detect the early phases of LRRK2 PD, as the symptoms of neurodegeneration are emerging, will be important to design enriched neuroprotective trials in at-risk carriers. 11 , 12 As it is not known which combination of symptoms are the first to emerge, it is unclear if the prodromal criteria derived from idiopathic PD apply to patients with LRRK2 PD, 13 as these heavily weight both REM sleep behaviour disorder (RBD) and hyposmia as high risk markers.…”

Genetic Analysis and Natural History of Parkinson’s Disease Due to the LRRK2 G2019S Variant

“…1,9 Precise phenoconversion rates have not been established. 10 Validating sensitive and specific prodromal criteria to detect the early phases of LRRK2 PD, as the symptoms of neurodegeneration are emerging, will be important to design enriched neuroprotective trials in at-risk carriers. 11,12 As it is not known which combination of symptoms are the first to emerge, it is unclear if the prodromal criteria derived from idiopathic PD apply to patients with LRRK2 PD, 13 as these weigh heavily both rapid eye movement sleep behavior disorder (RBD) and hyposmia as high risk markers.…”