Abstract
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Objectives To examine levels of neocortical and thalamic acetylcholinesterase (AChE) activity in Parkinson disease (PD) subjects relative to normal values in non-PD elderly.
Methods PD subjects (n=104, age 65.5±7.2, HY stage 2.4±0.6, MoCa score 26.0±2.4) and 29 control subjects (age 66.8 ± 10.9) underwent clinical and cognitive assessment and [11C]PMP AChE PET imaging. The 5th percentile cut-off of AChE activity in the non-PD elderly was used to define below normal range activity levels.
Results Patients with PD had lower mean neocortical (-9.9%, P<0.0001) and thalamic AChE (-9.7%, P=0.0004) activity compared to the control group. However, cholinergic denervation was heterogeneous with 65 patients (62.5%) having both normal range neocortical and thalamic AChE activity and the remainder combined neocortical and thalamic (n=12 or 12.5%), isolated neocortical (n=21, or 20.2%), or isolated thalamic (n=5 or 4.8%) AChE activity in the below normal range. The PD subgroup with low neocortical AChE activity levels had significantly worse cognitive performance compared to the normal range PD subgroup (F=16.0, P=0.0001). The PD subgroup with low thalamic AChE activity had higher frequency of patients with a history of falls (55.5% vs 22.1%, χ2=8.3, P=0.004) and symptoms of REM sleep behavior disorder (75.0% versus 36.4%, χ2=7.8, P=0.005) compared to the PD subgroup with normal range thalamic AChE activity.
Conclusions These findings indicate that cholinergic denervation is heterogeneous with evidence of below normal range cortical and/or thalamic AChE activity in 37.5% of patients with PD. Low level of cortical AChE is robustly associated with poor cognitive performance and low level of thalamic AChE activity with increased risk of falls and REM sleep behavior disorder compared to PD patients with normal range AChE activity.