June 6, 2026

@michaelokun

Can we measure Parkinson's disease progression years before diagnosis? An ‘alpha-synucleinopathy’ is a brain disease linked to abnormal accumulation of the protein alpha-synuclein and includes Parkinson's disease, dementia w/ Lewy bodies and multiple system atrophy. Monica Roascio and colleagues describe in a new paper in Brain how clinical changes in REM sleep behavior disorder (RBD) may be tracked years before the emergence of overt Parkinson's disease or dementia. Key points: - Using longitudinal data from 766 individuals w/ isolated REM sleep behavior disorder, the authors developed a model that tracks disease progression over time rather than relying on a single conversion event. - The model identified three markers reflecting earlier or later onset of progression, faster or slower progression, and whether motor or cognitive symptoms emerge first. - These progression markers were linked to established dopamine imaging biomarkers and to EEG measures of brain network dysfunction. My take: This study tackles one of the biggest challenges in neurodegeneration. We need better ways to measure progression before a person develops obvious Parkinson's disease or dementia. The traditional approach of waiting for ‘phenoconversion’ may miss many years of meaningful biological and clinical change. Continuous progression markers could ultimately improve clinical trials and help us identify who is worsening and when. Here are 5 points that resonated w/ me: 1- REM sleep behavior disorder remains one of the strongest known risk states for future Parkinson's disease and related disorders. 2- Motor changes appeared to worsen approximately 35% faster than cognitive changes in this cohort. 3- Clinical progression could be detected many years before traditional diagnostic milestones were reached. 4- Abnormal dopamine transporter imaging and abnormal EEG synchronization were linked to earlier and faster disease progression. 5- The future of disease-modifying trials may depend on continuous progression markers rather than waiting for a binary diagnosis of Parkinson's disease or dementia. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awag193/8698219