Objective: To determine whether cholinergic activity related to attention differs in males versus females in people with Parkinson’s disease (PwPD).

Background: Although cholinergic activity is lower than normal in PwPD and may explain attention deficits in PwPD, the role of sex is unknown. Sex differences in cholinergic activity exist in the central nervous system1 and these sex differences could be exacerbated by PD. We hypothesize that male, but not female, PwPD will have worse cholinergic activity and worse attention than the control participants.

Methods: 67 PD (70% male) and 21 control (38% male) participants completed the Attention Network Task (ANT) and the transcranial magnetic stimulation technique, short-latency afferent inhibition (SAI – a measure of cholinergic activity). All PwPD were tested “ON” medication. The ANT outcome variables include: accuracy, reaction time (RT), and the difference between the incongruent and congruent RTs (conflict). SAI is computed as the grand mean of the percent of the conditioned trials compared to the unconditioned trials.

Results: The male control participants had significantly better cholinergic activity (i.e. more inhibition of motor evoked response from somatosensory stimulation) compared to the male PD (PD: 77.59+/-19.84 control: 53.05+/-19.40, p=0.007) and female PD participants (PD: 79.66+/-21.94 control: 53.05+/-19.40, p=0.009)[Fig 1]. SAI was not different between any other groups. Male PD participants were significantly less accurate (male PD: 0.88+/-0.18 female PD: 0.98+/-0.01, p=0.013) and had a significantly longer RT (male PD: 813.08+/-128.73 female PD: 730.84+/-85.45, p=0.037) than PD females. ANT accuracy (rho=-0.312, p=0.019), RT (rho=0.290, p=0.030), and conflict (rho=0.366, p=0.006) were significantly correlated with the SAI for the male groups, indicating worse cholinergic activity is associated with worse attention. This relationship was not observed within the female groups.

Conclusions: These data suggest that sex may be a factor in the relationship between cholinergic and attention in PwPD. Considering that complex gait activities require increased attentional demand, male PD with cholinergic loss may be at a greater risk for falls than female with PD.

References: 1.Rhodes ME, Rubin RT. Functional sex differences (‘sexual diergism’) of central nervous system cholinergic systems, vasopressin, and hypothalamic-pituitary-adrenal axis activity in mammals: a selective review. Brain Res Brain Res Rev. 1999;30(2):135-152.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/role-of-sex-on-cholinergic-activity-and-attention-in-parkinsons-disease/