Association of specific biotypes in patients with Parkinson's disease and disease progression

Objective To identify biotypes in newly diagnosed Parkinson’s disease
patients and test whether these biotypes could explain inter-individual
differences in longitudinal progression. Methods In this longitudinal
analysis, we use a data-driven approach clustering PD patients from the
Parkinson’s Progression Markers Initiative (PPMI) (n = 314, age = 61.0 ±
9.5, 34.1% female, 5 years follow-up). Voxel-level neuroanatomical
features were estimated using deformation-based morphometry (DBM) of
T1-weighted MRI. Voxels whose deformation values were significantly
correlated (P < 0.01) with clinical scores (MDS-UPDRS-Parts I-III,
MDS-UPDRS-total, tremor score, and postural instability and gait
difficulty score) at baseline were selected. Then, these neuroanatomical
features were subjected to hierarchical cluster analysis. Changes in the
longitudinal progression and neuroanatomical pattern were compared between
different biotypes. Results Two neuroanatomical biotypes were identified:
(i) biotype 1 (n = 114) with subcortical brain volume as smaller than
heathy controls; (ii) biotype 2 (n = 200) with subcortical brain volumes
larger than heathy controls. Biotype 1 had more severe motor impairment,
autonomic dysfunction, and very much worse REM sleep behavior disorder
than biotype 2 at baseline. Although disease duration at initial visit and
follow-up were similar between biotypes, PD patients with smaller
subcortical brain volume had poorer prognosis, with more rapid decline in
several clinical domains and in dopamine functional neuroimaging over an
average of five years. Conclusion Robust neuroanatomical biotypes exist in
PD with distinct clinical and neuroanatomical pattern. These biotypes can
be detected at diagnosis, and predict the course of longitudinal
progression, which should benefit trial design and evaluation.