Olfactory Dysfunction in Fragile X Tremor Ataxia Syndrome

• Type of Material: Article
• Authors: Jorge Juncos, Emory University; Joash T Lazarus, Emory University; Julia Rohr, Emory University; Emily Graves Allen, Emory University; Lisa Shubeck, Emory University; Debra R Hamilton, Emory University; Gloria Novak, Emory University; Stephanie Sherman, Emory University
• Language: English
• Date: 2012-10
• Publisher: Wiley-Blackwell
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Movement Disorder Society
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/mds.25043/abstract
• Title of Journal or Parent Work: Movement Disorders
• ISSN: 0885-3185
• Volume: 27
• Issue: 12
• Start Page: 1556
• End Page: 1559
• Grant/Funding Information: This work was supported by the National Institutes of Health (grant nos.: RO1 HD29909 and P30 HD24064).
• Keywords: FXTAS; cognition; FMR1; ataxia; tremor; olfaction
• Research Categories: Biology, Genetics; Biology, Neuroscience

Abstract

Introduction We investigated olfactory defects in fragile X-associated tremor/ataxia syndrome (FXTAS), a finding reported on in other neurodegenerative disorders with clinical features that overlap those of FXTAS. Methods We measured olfactory identification capacity in 41 FMR1 premutation carriers and 42 controls using the University of Pennsylvania Smell Identification Test (UPSIT). Carriers received neurologic evaluations using motor rating scales for tremor, ataxia, and parkinsonism. Cognitive function was measured using the Montreal Cognitive Assessment test. Results Frequency of olfactory defects was higher in carriers, compared to controls (61% versus 29%; P = 0.003). There was no statistically significant group difference in severity of olfaction defects, after accounting for differences in age, and in rates of head injury and smoking. However, both the frequency (odds ratio = 3.9; 95% confidence interval: 0.81–19.1) and severity (28.6 versus 33.4; P = 0.01) of these defects were greater in cognitively impaired, compared to cognitively intact, carriers. There was no correlation between UPSIT scores and the above-mentioned motor rating scales. Conclusions FMR1 premutation carriers are susceptible to olfactory identification defects. The severity of these defects is comparable to that reported in hereditary ataxias, but less than that in PD and Alzheimer’s disease. This concurrence across neurodegenerative disorders suggests a shared system vulnerability that correlates with, but is not limited to, cognitive impairment, because it is also found in cognitively intact carriers. These results need to be corroborated in a larger prospective study of FMR1 premutation carriers that extends beyond olfactory identification to include measures of smell thresholds.