StimPD
Research type
Research Study
Full title
Stimulating brain circuits to treat Parkinson’s dementia
IRAS ID
351958
Contact name
Angeliki/A Zarkali
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2024/11/85 , UCL Data Protection Registration
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
Dementia is six times more common in Parkinson’s disease, affects over half of people living with Parkinson’s within 10 years, and has higher personal, societal and financial impact than other dementias. However, the mechanisms of Parkinson’s dementia remain unclear, and treatments extremely limited. Converging evidence suggests that Parkinson’s disrupts structural and functional brain circuits, so a promising approach for treating Parkinson’s dementia is to identify the brain circuits responsible and target them for intervention.
This study will use multimodal state-of-the art neuroimaging techniques in different populations of people with Parkinson's disease, to identify the brain circuits responsible for Parkinson’s dementia (Part 1) and apply novel non-invasive ultrasound stimulation on those circuits to improve cognition (Part 2, conditional to funding).Summary of work to be carried out
Part 1: We will apply recent advances in neuroimaging to identify structural and functional brain circuits responsible for Parkinson’s dementia using multiple independent sources of information. First, we will identify circuits that have been shown to respond to electrical stimulation, using a surgical technique called deep brain stimulation (DBS), leading to improvements in cognition post-operatively. DBS surgery is an effective treatment for motor symptoms but is invasive and considered unsuitable for people with cognitive impairment. Therefore, we will validate these findings in non-DBS Parkinson’s patients. Additionally, in a second experiment, we will use orthogonal, data-driven analyses in large number of patients with Parkinson's (not treated with DBS) who are followed up over time, to identify structural and functional brain circuits that are associated with cognitive decline over time. By combining these multiple sources of information from different patient populations, we will be able to select the best target for non-invasive stimulation of these circuits.
Part 2: We will use a novel technique called low intensity focused ultrasound (LIFU), to stimulate these circuits non-invasively. We will measure how ultrasound stimulation influences cognition in 50 Parkinson’s patients. We will use MR imaging to assess the effect of ultrasound stimulation on brain function and neurotransmitter levels short-term (immediately after stimulation) and longer-term, after 3 months. We predict that ultrasound stimulation of target circuits will lead to improvements in cognitive function, and sustained changes in brain function and neurotransmitter levels. Finally, using baseline brain MRI imaging, we will assess whether imaging markers that predict response to stimulation.
Potential applications and benefits
Together these experiments will help determine the optimal non-invasive stimulation targets to improve cognition in Parkinson’s, identify the patients most likely to benefit from this approach and directly test the efficacy of ultrasound stimulation as a therapeutic technique in Parkinson’s dementia.REC name
South Central - Oxford A Research Ethics Committee
REC reference
25/SC/0142
Date of REC Opinion
9 May 2025
REC opinion
Further Information Favourable Opinion