Olfactory identification in LRRK2 G2019S mutation carriers

a relevant marker?

the AJ LRRK2 Consortium

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated. Methods: We examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers. Results: Adjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: −3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (−12.8, −9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8% vs. 80.2%, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers. Interpretation: Therefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.

Original languageEnglish (US)
Pages (from-to)670-678
Number of pages9
JournalAnnals of Clinical and Translational Neurology
Volume1
Issue number9
DOIs
StatePublished - Sep 1 2014

Fingerprint

Parkinson Disease
Mutation
Smell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Olfactory identification in LRRK2 G2019S mutation carriers : a relevant marker? / the AJ LRRK2 Consortium.

In: Annals of Clinical and Translational Neurology, Vol. 1, No. 9, 01.09.2014, p. 670-678.

Research output: Contribution to journalArticle

@article{ceacbafd3aba42e3bc01977c5c947ad6,
title = "Olfactory identification in LRRK2 G2019S mutation carriers: a relevant marker?",
abstract = "Objective: Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated. Methods: We examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers. Results: Adjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: −3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (−12.8, −9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8{\%} vs. 80.2{\%}, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers. Interpretation: Therefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.",
author = "{the AJ LRRK2 Consortium} and Rachel Saunders-Pullman and Anat Mirelman and Cuiling Wang and Alcalay, {Roy N.} and {San Luciano}, Marta and Robert Ortega and Deborah Raymond and Helen Mejia-Santana and Laurie Ozelius and Lorraine Clark and Avi Orr-Utreger and Karen Marder and Nir Giladi and Bressman, {Susan B.}",
year = "2014",
month = "9",
day = "1",
doi = "10.1002/acn3.95",
language = "English (US)",
volume = "1",
pages = "670--678",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - Olfactory identification in LRRK2 G2019S mutation carriers

T2 - a relevant marker?

AU - the AJ LRRK2 Consortium

AU - Saunders-Pullman, Rachel

AU - Mirelman, Anat

AU - Wang, Cuiling

AU - Alcalay, Roy N.

AU - San Luciano, Marta

AU - Ortega, Robert

AU - Raymond, Deborah

AU - Mejia-Santana, Helen

AU - Ozelius, Laurie

AU - Clark, Lorraine

AU - Orr-Utreger, Avi

AU - Marder, Karen

AU - Giladi, Nir

AU - Bressman, Susan B.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Objective: Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated. Methods: We examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers. Results: Adjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: −3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (−12.8, −9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8% vs. 80.2%, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers. Interpretation: Therefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.

AB - Objective: Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated. Methods: We examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers. Results: Adjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: −3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (−12.8, −9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8% vs. 80.2%, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers. Interpretation: Therefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.

UR - http://www.scopus.com/inward/record.url?scp=84936993750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936993750&partnerID=8YFLogxK

U2 - 10.1002/acn3.95

DO - 10.1002/acn3.95

M3 - Article

VL - 1

SP - 670

EP - 678

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

SN - 2328-9503

IS - 9

ER -