Presence and intensity of tremor reflects subcortical cholinergic but not nigrostriatal dopaminergic innervation changes in Parkinson disease

Objectives Tremor in Parkinson disease (PD) is relatively unresponsive to dopaminergic replacements. A cholinergic component of tremor pathobiology is plausible because of the tremorolytic effects of anti-cholinergic drugs. We investigated the neurochemical basis of tremor in PD using vesicular monoaminergic type 2 (VMAT2) ligand (+)-α-[¹¹C]dihydrotetrabenazine (DTBZ) and acetylcholinesterase (AChE) substrate [¹¹C]methyl-4-piperidinyl propionate (PMP) PET imaging.

Methods PD patients, not on cholinergic medication, (Hoehn and Yahr stages I-III, n=42; mean age 64.7±6.8 years) underwent DTBZ and PMP brain PET imaging. PMP uptake ratio was calculated of late (>40 min) versus early (0-10 min) radiotracer retention. Average presence of tremor in the preceding week was assessed with the Movement Disorders Society (MDS) revised UPDRS rating scale.

Results MDS-UPDRS tremor score correlated with higher striatal (Rs=0.38, P=0.01) and cerebellar AChE (Rs=0.39, P=0.01) activity. There were no significant correlations between MDS-UPDRS tremor score and striatal VMAT2 ligand binding (Rs=0.08, P=0.63).

Conclusions Presence and intensity of tremor is associated with cholinergic subcortical but not with nigrostriatal dopaminergic innervation in PD.

Research Support NIH P01 NS01565