Gratwicke, JP; (2017) Can deep brain stimulation of the nucleus basalis of Meynert improve thinking and memory problems in Lewy body dementias? Doctoral thesis , UCL (University College London).

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Abstract

The Lewy body dementias, Parkinson’s disease dementia and dementia with Lewy bodies, are two of the most common causes of dementia worldwide, and share both a common clinical phenotype and underlying pathology. Despite their growing economic and societal disease burden, there are currently only a small number of limited symptomatic therapies available, while modern approaches to develop disease modifying biologic agents have so far produced little tangible effect. There is growing recognition of the need to explore alternative treatment avenues, and the success of deep brain stimulation (DBS) in modulating aberrant neural network processing to relieve symptoms in other neuropsychiatric diseases raises the possibility that this might be achievable in Lewy body dementias. The nucleus basalis of Meynert (NBM) provides the major source of ascending cholinergic innervation to the cortex, and is proposed to be a key node in multiple distributed cognitive networks. The nucleus degenerates significantly in Lewy body dementias, which correlates closely with the severity of cognitive decline. It is therefore proposed that deep brain stimulation to the NBM may be able to modulate cholinergic transmission to cortex, and thereby impact directly upon dementia symptoms. In this thesis I will present preliminary evidence from two experimental clinical trials of deep brain stimulation to the NBM in Lewy body dementias. I will present data showing that this invasive neurosurgical procedure is both safe and well tolerated in patients with advanced dementia, and that low frequency stimulation may be associated with improvements in both memory functions and neuropsychiatric symptomatology. Furthermore, I will present results from the first direct electrophysiological recordings from human NBM in vivo, showing that activity in the nucleus may reflect levels of sustained attention. Finally, I evaluate the overall clinical impact of this novel therapeutic approach in Lewy body dementias, and discuss how our electrophysiological findings may relate to this, and how they contribute to our existing understanding of the physiological function of NBM.

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