Risky driving and pedunculopontine nucleus-thalamic cholinergic denervation in Parkinson disease.
BACKGROUND
It is unknown whether driving difficulty in Parkinson disease (PD) is attributable to nigrostriatal dopaminergic or extranigral non-dopaminergic neurodegeneration.


OBJECTIVE
To investigate in vivo imaging differences in dopaminergic and cholinergic innervation between PD patients with and without a history of risky driving.


METHODS
Thirty non-demented PD subjects (10 women/20 men) completed a driving survey. These subjects had previously undergone (+)-[(11)C] dihydrotetrabenazine vesicular monoamine transporter 2 and [(11)C] methyl-4-piperidinyl propionate acetylcholinesterase PET imaging. Acetylcholinesterase PET imaging assesses cholinergic terminal integrity with cortical uptake largely reflecting basal forebrain and thalamic uptake principally reflecting pedunculopontine nucleus integrity.


RESULTS
Eight of thirty subjects reported a history of risky driving (been pulled over, had a traffic citation, or been in an accident since PD onset) while 22 had no such history (safe drivers). There was no difference in striatal dihydrotetrabenazine vesicular monoamine transporter uptake between risky and safe drivers. There was significantly less thalamic acetylcholinesterase activity in the risky drivers compared to safe drivers (0.0513 ± 0.006 vs. 0.0570 ± 0.006, p = 0.022) but no difference in neocortical acetylcholinesterase activity. Using multivariable logistic regression, decreased thalamic acetylcholinesterase activity remained an independent predictor of risky driving in PD even after controlling for age and disease duration.


CONCLUSIONS
Risky driving is related to pedunculopontine nucleus-thalamic but not neocortical cholinergic denervation or nigrostriatal dopaminergic denervation in PD. This suggests that degeneration of the pedunculopontine nucleus, a brainstem center responsible for postural and gait control, plays a role in the ability of PD patients to drive.
Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
Shiao-Pei S
SP
Weathers
Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
Vikas
V
Kotagal
Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
Nicolaas I
NI
Bohnen
Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: klchou@med.umich.edu.
Kelvin L
KL
Chou
D001334:Automobile Driving; D059329:Cholinergic Neurons / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000000981:diagnostic imaging* / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging* / Q000473:pathology; D045042:Pedunculopontine Tegmental Nucleus / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology
Driving; PET imaging; Parkinson disease