Longitudinal study of striatal aromatic l-amino acid decarboxylase activity in patients with idiopathic rapid eye movement sleep behavior disorder

Abstract

Study objectives: To determine if nigrostriatal dopaminergic system function, evaluated by aromatic l-amino acid decarboxylase (AADC) activity using 6-[¹⁸F]fluoro-meta-tyrosine brain positron emission tomography (FMT-PET) can accurately and efficiently identify idiopathic rapid-eye-movement behavior disorder (IRBD) individuals at risk for conversion to a clinical diagnosis of Parkinson's disease (PD) or dementia with Lewy bodies (DLB).

Methods: We assessed prospectively striatal aromatic l-amino acid decarboxylase activity using FMT brain PET imaging in IRBD patients who were followed systematically every 1-3 months for 1-10 years. IRBD patients (n = 27) were enrolled in this prospective cohort study starting in 2009. Those who underwent follow-up scans between January 2011 and September 2014 (n = 24) were analyzed in the present study.

Results: Of the 24 IRBD patients with baseline and follow-up FMT-PET scans, 11 (45.8%) developed PD (n = 6) or DLB (n = 5). Compared to IRBD patients who were still disease-free, those who developed PD (n = 5) or DLB with parkinsonism (n = 1) had significantly reduced bilateral putaminal FMT uptake during the follow-up. Furthermore, the rate of FMT decline between baseline and follow-up scans was higher in all converted patients, even for those with DLB without parkinsonism, than in IRBD patients who remained disease-free.

Conclusions: FMT-PET, which represents a dynamic change in AADC activity over time, may also be a useful predictor for the risk of conversion to PD or DLB over short-term clinical follow-up periods, or when testing neuroprotective and restorative strategies in the prodromal phases of PD or DLB.

Keywords: 6-[(18)F]fluoro-meta-tyrosine brain PET (FMT-PET); Aromatic l-amino acid decarboxylase activity (AADC); Dementia with Lewy bodies; Lewy body disease; Parkinson's disease; REM sleep behavior disorder.