Gamma connectivity predicts response to intermittent Theta Burst Stimulation in Alzheimer’s disease: A randomised controlled trial

Alzheimer’s disease is characterised by progressive cognitive decline for which there are currently no effective treatments. There is growing evidence that neural network dysfunction is a likely proximate cause of cognitive impairment in Alzheimer’s and, as such, may represent a promising therapeutic target. Here we investigated whether a course of intermittent Theta Burst Stimulation (iTBS) could modulate functional connectivity and cognitive function in mild to moderate Alzheimer’s disease. Fifty-eight participants were randomised to receive a course of either active or sham iTBS. Stimulation was applied to four brain sites sequentially in each treatment session: left DLPFC, right DLPFC, left PPC, and right PPC. Neurobiological (EEG), cognitive (CogState, ADASCog), and functional (QoL-AD, GDS) assessments were undertaken at baseline and end of treatment. Cognitive and functional assessments were also conducted at 3-months (blinded) and 6-months (active group only) following end of treatment. Active iTBS resulted in a significant and large increase in resting state gamma connectivity as well as improved delayed recall on an episodic memory task. Both baseline gamma connectivity, and change in gamma connectivity, were found to be predictive of improved delayed recall following active treatment. These findings support future research into iTBS for the treatment of Alzheimer’s disease focussing on protocol optimisation.