Discriminating between proposed Brain-First and Body-First Parkinson's disease using conventional and...

Two Parkinson's disease subtypes-"Brain-First" and "Body-First"-have been proposed based on putative sites of onset. We examined whether "Body-First" markers relate to more symmetric striatal [¹²³I]-FP-CIT uptake and whether imaging could discriminate the subtypes. In a retrospective cohort of 158 de novo PD patients imaged at diagnosis and followed for six years, patients were classified as "Body-First" if baseline REM sleep behavior disorder, constipation, or neurogenic orthostatic hypotension was present. DaTQUANT provided semiquantitative metrics; a radiomics-based classifier was also trained on DAT-SPECT images. Neither asymmetry indices nor other DaTQUANT measures differed between groups (all p > 0.05). Radiomics showed poor discrimination (AUC ≈ 0.46). Clinically, "Body-First" patients displayed a more adverse course, with higher MCI prevalence and greater MMSE decline and neuropsychiatric burden, whereas motor severity and complications were comparable between groups. These data suggest DAT-SPECT-conventional or radiomics-enhanced-does not separate proposed subtypes at diagnosis, although "Body-First" features forecast worse non-motor progression.