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November 04, 2014; 83 (19) Article

Imaging prodromal Parkinson disease

The Parkinson Associated Risk Syndrome Study

Danna Jennings, Andrew Siderowf, Matthew Stern, John Seibyl, Shirley Eberly, David Oakes, Kenneth Marek, For the PARS Investigators
First published October 8, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000960
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Abstract

Objectives: The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD).

Methods: In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [123I]β-CIT striatal binding ratio in hyposmic and normosmic subjects.

Results: Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11% of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to >40%.

Conclusion: Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD.

GLOSSARY

CI=
confidence interval;
DAT=
dopamine transporter;
[123I]β-CIT=
iodine-123 labeled 2β-carbomethoxy-3β-(4-iodophenyl)tropane;
OR=
odds ratio;
PARS=
Parkinson Associated Risk Syndrome;
PD=
Parkinson disease;
RBD=
REM behavior disorder;
SRS=
Symptom Rating Scale;
UPDRS=
Unified Parkinson’s Disease Rating Scale;
UPSIT=
University of Pennsylvania Smell Identification Test

Footnotes

  • PARS coinvestigators are listed on the Neurology® Web site at www.neurology.org.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received April 9, 2014.
  • Accepted in final form August 7, 2014.
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Letters: Rapid online correspondence

  • Response to Mullen et al.
    • Danna Jennings, Senior Clinical Research Director, Institute for Neurodegenerative Disorders
    • Andrew Siderowf, MD; Matthew Stern, MD; John Seibyl, MD; Shirley Eberly, MS; David Oakes, PhD; Kenneth Marek, MD
    Submitted March 11, 2015
  • Hyposmia as a sensitive but non-specific marker for early neurodegeneration
    • Martijn L.T.M. Muller, Research Assistant Professor, University of Michigan
    • Roger L. Albin, University of Michigan & VAAAHS, Ann Arbor, MI; Nicolaas I. Bohnen, University of Michigan & VAAAHS Ann Arbor, MI
    Submitted November 18, 2014
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