Why patients with Alzheimer's disease may show increased sensitivity to tropicamide eye drops: role of locus coeruleus

Rationale: Patients suffering from Alzheimer's disease (AD) may show increased sensitivity to tropicamide, a muscarinic cholinoceptor antagonist. AD is associated with a severe loss of noradrenergic neurones in the locus coeruleus (LC), which can be switched off experimentally by the alpha(2)-adrenoceptor agonist clonidine. The possibility arises that increased pupillary sensitivity to tropicamide in AD may be due to diminished LC activity. Objective: To examine the hypothesis that clonidine may potentiate tropicamide-evoked mydriasis. Materials and methods: Sixteen healthy male volunteers participated in two experimental sessions (0.2 mg clonidine or placebo) conducted 1 week apart. In each session tropicamide (0.01% 10 mu lx2) was applied to the left eye and artificial tear (10 mu lx2) was applied to the right eye. Pupillary functions (resting pupil diameter and light and darkness reflexes), alertness and non-pupillary autonomic functions (blood pressure, heart rate, core temperature and salivary output) were measured. Data were analysed by ANOVA, with multiple comparisons. Results: Tropicamide increased resting pupil diameter, velocity and amplitude of the darkness reflex response, and decreased recovery time of the light reflex response. Clonidine affected all these pupillary measures in the opposite direction with the exception of the recovery time. The mydriatic response to tropicamide was potentiated by pre-treatment with clonidine. Clonidine reduced critical flicker fusion frequency, subjective alertness, blood pressure, salivation and temperature. Conclusions: The potentiation of tropicamide-evoked pupil dilatation by clonidine may be due to the abolition of the increase in parasympathetically mediated pupil constriction due to reduced LC activity.