Fluctuating cognition are very common in patients with Alzheimer-related Lewy body dementias (LBD). Such fluctuations in attention and alertness are a major source of disability in the patients and a marked stressor for caregivers. Our preliminary data point to cholinergic topographic vulnerability that involves the cingulo-opercular alertness network in LBD. This brain network plays an important role in maintenance of alertness and may be implicated as a neural substrate underlying cognitive fluctuations in patients with LBD. The overarching goal of this study is to test the hypothesis that cholinergic vulnerability of the cingulo-opercular alertness network underlies cognitive fluctuations in patients with LBD. We will test this hypothesis by a) correlating in vivo [18F]FEOBV VAChT PET binding in the cingulo-opercular alertness network with measures of cognitive fluctuation, and b) examine the effect of target engagement of vulnerable cholinergic hubs of this network by transcranial direct current neurostimulation (tDCS) excitation on cognitive fluctuations. Positive findings of this study could encourage future clinical trials of targeted non-invasive neurostimulation of this neural network using tDCS as an adjunct to cholinergic pharmacotherapy to manage fluctuations in alertness in people with LBD.
Fluctuations in alertness are very common in persons with Lewy body dementias and are a major source of disability. Changes in a chemical messenger molecule called acetylcholine within certain brain regions may play a role in these fluctuations. We propose to test this hypothesis and also determine whether a non-invasive way of stimulating affected brain regions may be of relevance for future management of these fluctuations.
