Preemptive treatment in the prodromal phase of Lewy body disease

Abstract

Lewy body disease (LBD), including Parkinson disease (PD) and dementia with Lewy bodies, begins with α–synuclein aggregation 10–20 years before symptoms appear. Prodromal features―constipation, REM sleep behavior disorder, and olfactory dysfunction―enable early detection. In the NaT–PROBE study of over 21,000 health screening examinees aged 50 and above, 6.8% were identified as high risk based on multiple prodromal signs. These individuals showed subtle motor and cognitive impairments and had a higher likelihood of abnormal DaT–SPECT and cardiac MIBG scintigraphy compared to low–risk subjects. Notably, Alzheimer's disease–related plasma biomarkers remained unchanged during this phase despite neurodegeneration. A multicenter, randomized, placebo–controlled trial is underway to evaluate the efficacy and safety of zonisamide in high–risk individuals. Early intervention in the prodromal stage may shift the paradigm in managing neurodegenerative disorders.