Cognitive Impairment and Autonomic Ganglionopathy

Laurie L. Barclay, MD


June 05, 2012

Autoimmune Autonomic Ganglionopathy With Reversible Cognitive Impairment

Gibbons CH, Centi J, Vernino S, Freeman R
Arch Neurol. 2012;69:461-466

Study Summary

Autoimmune autonomic ganglionopathy (AAG) is a rare form of severe autonomic failure linked to impaired transmission across the autonomic ganglia, caused by autoantibodies directed against the ganglionic nicotinic acetylcholine receptor. Although cognitive impairment is not a characteristic feature, some patients with AAG report cognitive impairment of unclear etiology even after treatment of autonomic symptoms. The goal of this prospective study was to evaluate the association among orthostatic hypotension, nicotinic acetylcholine receptor autoantibody titers, and cognitive impairment in patients with AAG.

At an academic medical center, 3 patients with AAG had neuropsychological testing in seated and standing positions before and after cycles of plasma exchange. Orthostatic hypotension and increased antibody titers were independently associated with neuropsychological impairment (P < .05). This association was especially pronounced in the domains of executive function, sustained attention, and working memory. Once the nicotinic acetylcholine receptor autoantibody titer decreased after plasmapheresis, however, cognitive dysfunction improved, even in the seated normotensive position.


In a small case series of patients with AAG, reversible cognitive impairment was independently associated with orthostatic hypotension and elevated titers of nicotinic acetylcholine receptor autoantibodies. These findings shed light on additional clinical manifestations of AAG and draw attention to a potentially treatable cause of cognitive impairment.

Study limitations include the small sample size, as a result of the rarity of AAG; cerebrospinal fluid studies done in only 1 patient; possible practice effects on cognitive test results; and possible placebo effects. In addition, the study design did not allow determination of the relative contribution of orthostatic hypotension and of elevated nicotinic acetylcholine receptor antibody titers to cognitive impairment. The improvement in cognitive scores after plasma exchange in both the upright and seated positions suggests that cognitive impairment is reversible in patients with AAG and may have implications for other forms of cognitive impairment associated with autoantibodies.



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