To differentiate between brain and body-first alpha-synucleinopathies and to describe their clinical characteristics.

A brain- vs body-first hypothesis has been proposed to identify where the alpha-synuclein deposits initially aggregate in alpha-synucleinopathies.

We used the Rochester Epidemiology Project (REP) to establish a population-based cohort of alpha-synucleinopathies in Olmsted County (MN) 1991-2005. A movement disorder specialist reviewed all medical charts to confirm the clinical diagnoses of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and Parkinson’s disease dementia (PDD). Multiple system atrophy (MSA) was not included in this study due to a low number of patients with this diagnosis in our cohort.
The presence of at least 2 of the following symptoms before the onset of the motor symptoms helped us define the body-first group as compared to the brain-first group who had none of them: constipation, erectile dysfunction, REM sleep behavior disorder, anosmia, and neurogenic bladder.

Brain-first patients (n=228) were more likely to have PD than body-first patients (OR= 2.51, p= 0.004), whereas body-first patients (n=50) were more likely to have DLB (OR= 5.19, p< 0.001). PDD was not associated with either sub-groups (p= 0.09).
Body-first patients did not have higher rates of tremor (OR= 0.55, p= 0.06), bradykinesia (OR= 0.87, p= 0.84), and rigidity (OR= 0.92, p= 0.85) as compared to the brain-first group. Similarly, there were no differences in the risk of dyskinesia (HR= 1.43, p= 0.28) and risk of death (HR= 0.89, p= 0.497) between groups.

In our population-based cohort of alpha-synucleinopathies, brain-first patients were more likely to develop PD compared to body-first patients, and body-first patients were more likely to develop DLB. No significant differences among motor symptoms as well as risk of developing dyskinesia and risk of death were observed in our cohort between groups.