Probing peripheral and central cholinergic system responses

Objective: The pharmacological response to drugs that act on the cholinergi c system of the iris has been used to predict deficits in central cholinerg ic functioning due to diseases such as Alzheimer's disease, yet correlation s between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (I) the tropicamide-induc ed increase in pupil diameter, and (2) the reversal of this effect with pil ocarpine. Scopolamine was used as a positive control to detect age-dependen t changes in central cholinergic functioning in the elderly. Design: Random ized double-blind controlled trial. Participants: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. Interventions: Pupil diamete r was monitored using a computerized infrared pupillometer over 4 hours. Th e study involved 4 sessions. In I session, tropicamide (20 mu L, 0.01%) was administered to one eye and placebo to the other. In another session, trop icamide (20 mu L, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 mu L, 0.1%) to one eye and pla cebo to the other. All eye drops were given in a randomized order. In 2 sep arate sessions, a single dose of scopolamine (0.5 mg, intravenously) or pla cebo was administered, and the effects on word recall were measured using t he Buschke Selective Reminding Test over 2 hours. Outcome measures: Pupil s ize at time points after administration of tropicamide and pilocarpine; sco polamine-induced impairment in word recall. Results: There was no significa nt difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a signific antly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 a nd 215 minutes after administration, compared with the young group (p < 0.0 5). Compared with the young group, the elderly group had greater scopolamin e-induced impairment in word recall 60, 90 and 120 minutes after administra tion (p < 0.05). Conclusion: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be us eful to assess variations in central cholinergic function in elderly patien ts.