Olfactory dysfunction is associated with neuropsychiatric manifestations in Parkinson's disease

Authors

  • James F. Morley MD, PhD,

    1. Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania, Philadelphia, PA
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  • Daniel Weintraub MD,

    1. Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania, Philadelphia, PA
    3. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
    4. Mental Illness Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA
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  • Eugenia Mamikonyan MS,

    1. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
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  • Paul J. Moberg PhD,

    1. Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania, Philadelphia, PA
    3. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
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  • Andrew D. Siderowf MD,

    1. Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania, Philadelphia, PA
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  • John E. Duda MD

    Corresponding author
    1. Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania, Philadelphia, PA
    • Philadelphia Veterans Administration Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104
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  • Funding agencies: This work was supported by NIH grant K23 MH067894 (to D.W.).

  • Relevant conflicts of interest/financial disclosures: Dr. Morley has received travel funding from Teva Pharmaceutical Industries Ltd. Dr. Weintraub has served on a scientific advisory board for Boehringer Ingelheim; serves on the editorial board of Movement Disorders; has received speaker honoraria from Boehringer Ingelheim, ACADIA Pharmaceuticals, Novartis, Osmotica Pharmaceutical Corp., BrainCells Inc., Merck Serono, Sanofi-aventis, and Pfizer Inc; and has received/receives research support from Avid Radiopharmaceuticals, Inc., Boehringer Ingelheim, National Institutes of Health (NIMH K23 MH067894 [PI], NINDS P50 NS053488-01 [coinvestigator], NIA RO1AG031348 [site PI], and NINDS R01NS065087 [coinvestigator]), and from the Michael J. Fox Foundation for Parkinson's Research. Ms. Mamikonyan reports no disclosures. Dr. Siderowf serves on a scientific advisory board for, and has received speaker honoraria from, Teva Pharmaceutical Industries Ltd.; serves as a consultant for Supernus Pharmaceuticals, Inc.; and receives research support from Avid Radiopharmaceuticals, Inc., the NIH (NINDS U10 NS044451-023 [Site PI], NINDS P50 NS053488-01 [cocore leader and project leader], NINDS R43NS0636071 [site PI], and NINDS R01NS065087 [coinvestigator]), and from the Institute for Neurodegenerative Disorders. Dr. Duda serves on a grant review panel for the Michael J. Fox Foundation for Parkinson's Research; receives research support from the U.S. Department of Veterans Affairs (Merit Award [PI]), the Michael J. Fox Foundation, and the Samueli Institute; and holds stock in C.R. Bard, Inc., Celgene, Clarient, Inc., and Johnson & Johnson. Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Hyposmia, psychiatric disorders, and cognitive problems are common nonmotor manifestations in Parkinson's disease, but how they are related remains unclear. We investigated the relationship between olfactory dysfunction and neuropsychiatric manifestations and performed a cross-sectional study of 248 patients at two movement disorders clinics at academic medical centers. Psychiatric measures were the Geriatric Depression Scale-15, Inventory of Depressive Symptomatology, State Anxiety Inventory, Apathy Scale, and Parkinson's Psychosis Rating Scale. Cognitive measures were the Mini–Mental State Examination, Hopkins Verbal Learning Test–Revised, Digit Span, Tower of London-Drexel, and the Stroop Color Word Test. Olfaction was tested with the University of Pennsylvania Smell Identification Test. There was no significant association between olfaction and mood measures, but psychotic symptoms were more common in patients with olfaction scores below the median (30% vs. 12%; P < 0.001). Worse olfaction was associated with poorer memory (Hopkins Verbal Learning Test–Revised delayed recall items: mean [standard deviation], 6.2 [3.2] vs. 8.4 [2.8]; P < 0.001) and executive performance (Tower of London total moves, 52 [38] vs. 34 [21]; P < 0.001). Odor-identification score was a significant predictor of abnormal performance on these cognitive tests after adjustment for age, sex, and disease characteristics in logistic regression models. The relationship between hyposmia, psychosis, and specific cognitive impairments may reflect the anatomic distribution of Lewy pathology and suggests that olfactory dysfunction could be a biomarker of additional extranigral disease. Future prospective studies are warranted to assess whether hyposmia, a very early feature of Parkinson's disease, might be used to predict the appearance of other common nonmotor symptoms. © 2011 Movement Disorder Society

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