Enhanced cutaneous vascular response in AD subjects under donepezil therapy

Objective: Abnormal cutaneous vasodilatory responses to the iontophoresis of vasodilators were previously observed in Alzheimer’s disease (AD). We sought to replicate these observations and further identify peripheral vascular components of AD pathology. Methods: Methacholine chloride (MCh), acetylcholine chloride (ACh), and sodium nitroprusside (SNP) were applied iontophoretically to forearm skin. Laser Doppler imaging of treated areas yielded total perfusion response values. Results: Response to MCh was enhanced 78% (P=0.003) in AD subjects under therapy with the acetylcholinesterase inhibitor (AChEI) donepezil (N=9), relative to age- and sex-matched controls (N=12). Significant increases in perfusion were also observed after application of ACh (68%, P=0.03) and SNP (46%, P=0.04). Conclusions: A previous study reported attenuated response to ACh in AD. Paradoxically, we observed a substantially enhanced response that is likely a consequence of donepezil therapy. The increased response to the endothelium-independent vasodilator SNP indicates improved general vasodilatory response, perhaps due to preservation of endogenous ACh by donepezil. Cerebral perfusion in response to functional activation may be improved in this way, suggesting a secondary therapeutic mode of donepezil.