Journal article
Clustering of Motor and Nonmotor Traits in Leucine-Rich Repeat Kinase 2 G2019S Parkinson's Disease Nonparkinsonian Relatives: A Multicenter Family Study
Movement disorders, Vol.33(6), pp.960-965
06/01/2018
DOI: 10.1002/mds.27272
PMID: 29665080
Abstract
Objectives: The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first-degree relatives of PD leucinerich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features.
Methods: We included nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases and unrelated healthy controls participating in established multiplex family LRRK2 cohorts. Study participants underwent neurologic assessment including cognitive screening, olfaction testing, and questionnaires for daytime sleepiness, depression, and anxiety. We used a multiple logistic regression model with backward variable selection, validated with bootstrap resampling, to establish the best combination of motor and nonmotor features that differentiates nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases from unrelated healthy controls.
Results: We included 142 nonparkinsonian family members and 172 unrelated healthy controls. The combination of past or current symptoms of anxiety (adjusted odds ratio, 4.16; 95% confidence interval, 2.01-8.63), less daytime sleepiness (adjusted odds ratio [1 unit], 0.90; 95% confidence interval, 0.83-0.97], and worse motor UPDRS score (adjusted odds ratio [1 unit], 1.4; 95% confidence interval, 1.20-1.67) distinguished nonparkinsonian family members, regardless of LRRK2 G2019S mutation status, from unrelated healthy controls. The model accuracy was good (area under the curve=79.3%).
Conclusions: A set of motor and nonmotor features distinguishes first-degree relatives of LRRK2 G2019S probands, regardless of mutation status, from unrelated healthy controls. Environmental or non-LRRK2 genetic factors in LRRK2-associated PD may influence penetrance of the LRRK2 G2019S mutation. The relationship of these features to actual PD risk requires longitudinal observation of LRRK2 familial PD cohorts. (C) 2018 International Parkinson and Movement Disorder Society
Details
- Title: Subtitle
- Clustering of Motor and Nonmotor Traits in Leucine-Rich Repeat Kinase 2 G2019S Parkinson's Disease Nonparkinsonian Relatives: A Multicenter Family Study
- Creators
- Tiago A. Mestre - Toronto Western HospitalClaustre Pont-Sunyer - University of BarcelonaFarah Kausar - Parkinson's Institute and Clinical CenterNaomi P. Visanji - Toronto Western HospitalTaneera Ghate - Toronto Western HospitalBarbara S. Connolly - Toronto Western HospitalCarmen Gasca-Salas - Centro Integral en Neurociencias Abarca Cidón, Hospitales de Madrid Hospitales Puerta del SurCEU San Pablo UniversityMadrid Spain (current affiliation)Drew S. Kern - Toronto Western HospitalJennifer Jain - Toronto Western HospitalElizabeth J. Slow - Toronto Western HospitalAchinoam Faust-Socher - Toronto Western HospitalMeike Kasten - University of LübeckPettarusp M. Wadia - Toronto Western HospitalCindy Zadikoff - Toronto Western HospitalPrakash Kumar - Toronto Western HospitalRonald M. de Bie - Toronto Western HospitalTeri Thomsen - Toronto Western HospitalAnthony E. Lang - Toronto Western HospitalBirgitt Schule - Parkinson's Institute and Clinical CenterChristine Klein - University of LübeckEduardo Tolosa - University of BarcelonaConnie Marras - Toronto Western Hospital
- Resource Type
- Journal article
- Publication Details
- Movement disorders, Vol.33(6), pp.960-965
- DOI
- 10.1002/mds.27272
- PMID
- 29665080
- NLM abbreviation
- Mov Disord
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Publisher
- Wiley
- Number of pages
- 6
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Neurology
- Record Identifier
- 9984303024202771
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