Marguerite Wieler1, Myrlene Gee2, W R Wayne Martin3. 1. Division of Neurology, University of Alberta, Edmonton, Alberta, Canada. 2. Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. 3. Division of Neurology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: wmartin@ualberta.ca.
Abstract
OBJECTIVE: To determine whether, in patients with early Parkinson's disease (PD), longitudinal changes in midbrain iron content are associated with declining motor function over a period of three years. METHODS: Nineteen untreated subjects with early PD and 13 age- and sex-matched controls were followed clinically for 36 months. MRI with a 3 T magnet was performed at baseline, 18 months and 36 months with a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate R2*. R2* was calculated for midbrain and forebrain basal ganglia regions. RESULTS: A difference in R2* between patients and controls was observed at baseline (p = 0.035) but not at 18 or 36 months in the lateral substantia nigra pars compacta (SNc). Linear regression indicated significant correlations between the change in R2* in the lateral SNc and the change score in UPDRS III (p = 0.008) and the PDQ-39 -mobility sub-score (p = 0.03) from baseline to 36 months. R2* tended to increase in those with more advanced disease and to decrease in those with milder disease. CONCLUSIONS: High field MRI demonstrates lateral SNc abnormalities that progress over 3 years in early PD consistent with increased iron content in those with more advanced disease, corresponding to the known distribution of neuronal loss occurring in this disorder, and correlating with motor symptomatology. Larger and longer investigations with more precise mapping of iron-containing midbrain structures are needed to fully evaluate the potential of R2* as a biomarker of disease progression in PD.
OBJECTIVE: To determine whether, in patients with early Parkinson's disease (PD), longitudinal changes in midbrain iron content are associated with declining motor function over a period of three years. METHODS: Nineteen untreated subjects with early PD and 13 age- and sex-matched controls were followed clinically for 36 months. MRI with a 3 T magnet was performed at baseline, 18 months and 36 months with a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate R2*. R2* was calculated for midbrain and forebrain basal ganglia regions. RESULTS: A difference in R2* between patients and controls was observed at baseline (p = 0.035) but not at 18 or 36 months in the lateral substantia nigra pars compacta (SNc). Linear regression indicated significant correlations between the change in R2* in the lateral SNc and the change score in UPDRS III (p = 0.008) and the PDQ-39 -mobility sub-score (p = 0.03) from baseline to 36 months. R2* tended to increase in those with more advanced disease and to decrease in those with milder disease. CONCLUSIONS: High field MRI demonstrates lateral SNc abnormalities that progress over 3 years in early PD consistent with increased iron content in those with more advanced disease, corresponding to the known distribution of neuronal loss occurring in this disorder, and correlating with motor symptomatology. Larger and longer investigations with more precise mapping of iron-containing midbrain structures are needed to fully evaluate the potential of R2* as a biomarker of disease progression in PD.
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