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. 2015 Jun;30(7):981-6.
doi: 10.1002/mds.26213. Epub 2015 Mar 21.

Nonmotor symptoms in healthy Ashkenazi Jewish carriers of the G2019S mutation in the LRRK2 gene

Anat Mirelman  1 , Roy N Alcalay  2   3 , Rachel Saunders-Pullman  4   5 , Kira Yasinovsky  1 , Avner Thaler  1 , Tanya Gurevich  1   6 , Helen Mejia-Santana  2 , Deborah Raymond  4 , Mali Gana-Weisz  7 , Anat Bar-Shira  7 , Laurie Ozelius  8 , Lorraine Clark  9   10 , Avi Orr-Urtreger  6   7 , Susan Bressman  4   5 , Karen Marder  2   3 , Nir Giladi  1   6   11 ; LRRK2 AJ consortium
Affiliations

Nonmotor symptoms in healthy Ashkenazi Jewish carriers of the G2019S mutation in the LRRK2 gene

Anat Mirelman et al. Mov Disord. 2015 Jun.

Abstract

Background: The asymptomatic carriers of the Leucine rich repeat kinase 2 (LRRK2) G2019S mutation represent a population at risk for developing PD. The aim of this study was to assess differences in nonmotor symptoms between nonmanifesting carriers and noncarriers of the G2019S mutation.

Methods: Two hundred fifty-three subjects participated in this observational cross-sectional multicenter study. Standard questionnaires assessing anxiety, depression, cognition, smell, nonmotor symptoms, and rapid eye movement (REM) sleep behavior were administered. Analyses were adjusted for age, sex, family relations, education, and site.

Results: One hundred thirty-four carriers were identified. Carriers had higher nonmotor symptoms score on the Nonmotor symptoms (NMS) questionnaire (P = 0.02). These findings were amplified in carriers older than age 50 y, with higher nonmotor symptoms scores and trait anxiety scores (P < 0.03).

Conclusions: In this cross-section study, carriers of the G2019S LRRK2 mutation endorsed subtle nonmotor symptoms. Whether these are early features of PD will require a longitudinal study. © 2015 International Parkinson and Movement Disorder Society.

Keywords: LRRK2; Non-manifesting carriers; Parkinson's disease; prodromal.

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Conflict of interest statement

Disclosure: The authors report no conflicts of interest.

Dr. Mirelman, Ms. Yasinovsky, Dr. Thaler, Dr. Gurevich, Ms. Mejia-Santana, Ms. Raymond, Dr. Gana-Weisz, Dr. Bar-Shira, Dr. Orr-Urtreger, and Dr. Giladi have nothing to disclose.

Dr. Alcalay receives research support from the NIH (K02NS080915), the Parkinson’s disease Foundation, the Smart Foundation and the Michael J Fox foundation.

Dr. Saunders-Pullman serves on the Scientific Advisory Board of the Dystonia Medical Research Foundation. She receives research support from the NIH (K02 NS073836), the Michael J Fox Foundation for Parkinson’s Research, the Bachmann-Strauss Dystonia and Parkinson’s Foundation, and the Marcled Foundation. Dr. Ozelius receives salary support from NIH [NS037409, NS075881, DC011805]. She is a current member of the scientific advisory boards of the National Spasmodic Dysphonia Association, the Benign Essential Blepharospasm Research Foundation and Tourette Syndrome Association, Inc. Dr.

Ozelius receives royalty payments from Athena Diagnostics related to patents. Dr. Clark receives research support from the NIH [NINDS #R01 NS060113 (principal investigator), NINDS #R01 NS073872 (Co-principal investigator), NIA #5P50AG008702(Project 3, principal investigator), and NINDS #NS36630 (co-investigator) and 2P50NS038370-11 (Co-Investigator)], and the Parkinson’s Disease Foundation (principal investigator) and the Michael J Fox Foundation (co-investigator).

Dr. Bressman serves on the advisory boards of the Michael J. Fox Foundation, the Dystonia Medical Research Foundation, the Bachmann Strauss Dystonia and Parkinson’s Foundation, and the Board of We Move. She has consulted for Bristol Meyer Squibb. She has received research support from the Michael J. Fox Foundation, National Institutes of Health (NIH), and Dystonia Medical Research Foundation.

Dr. Marder receives research support from the NIH [#NS036630 (PI), 1UL1 RR024156-01(Director PCIR), PO412196- G (Co-I), and PO412196-G (Co-I)]. She received compensation for participating on the steering committee for U01NS052592 and from the Parkinson Disease Foundation, Huntington’s Disease Society of America, the Parkinson Study Group, CHDI, and the Michael J Fox foundation.

References

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