Brain tumour patients with low-grade gliomas live for years with cognitive deficits that have no reliable treatment. This project tests whether repeated magnetic pulses delivered to the scalp—a technique already approved for depression—can improve their memory, attention, and thinking. The problem is stark: roughly 247 patients with low-grade gliomas will first complete online cognitive tests to map the range and severity of their deficits. Those data, combined with MRI scans, will produce a brain map showing exactly where damage causes specific cognitive problems. Then 52 patients with clear deficits will be randomised to receive either 12 sessions of transcranial magnetic stimulation over four weeks or no treatment, with cognitive performance and brain network activity tracked for three months. If rTMS shows measurable cognitive improvement, this proof-of-concept study will provide the effect-size data needed to design a larger efficacy trial. That could eventually give clinicians a non-invasive, drug-free tool to preserve quality of life, employment, and social function for a patient group that currently has no options. The remote testing methods developed here could also make cognitive assessment more accessible for brain tumour patients nationwide.
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Background: Patients with brain tumours suffer from debilitating long-term cognitive deficits affecting their quality-of-life, employment, and social lives. There are no reliable treatments. The Brain Tumour Charity and the James Lind Alliance neuro-oncology research priorities identified that understanding and addressing cognitive deficits are a patient research priority. Patients with Low Grade Gliomas (LGG) have a particularly high burden of cognitive deficits due to the intrinsic nature of LGG within the brain. They are younger with relatively long survival and therefore suffer from these deficits for many years. Repetitive Transcranial Magnetic Stimulation (rTMS) involves the non-invasive delivery of magnetic pulses to the brain inducing changes to functional connectivity. rTMS is NICE approved for depression and CE marked for chronic pain. It is a provided clinical service in our hospital in Liverpool. In a randomised sham-controlled clinical trial in patients with brain tumours, rTMS was shown to improve arm weakness after surgery. rTMS has been shown to be safe and improve cognition in patients with Alzheimer's disease, Mild Cognitive Impairment, and Post-Stroke Cognitive Impairment. This research fellowship has been developed in partnership with patients with LGG. Primary research question: Can rTMS induce cognitive improvements in patients with LGG? Work package 1 (WP1): Cross-sectional assessment of cognitive deficits in patients with LGG 247 patients living with LGG from the last 10-years will be invited to remotely complete an online battery of objective cognitive assessments (CANTAB tests) and a measure of subjective cognition (FACT-Cog). The objective assessments will be compared with normative data from healthy populations. This cross-sectional cognitive data will be combined with routinely available clinical variables to describe predictors of cognitive deficits. WP2: Produce a cognitive deficits brain map Cognitive and clinical data from WP1 will be combined with routinely available post-operative FLAIR and T1 MRI scans. This will be used to produce a voxel-based lesion-deficit probability map. WP3: Proof-of-concept study: Evaluate whether rTMS induces cognitive changes in patients with LGG Population: Patients from WP1 (n=52) with cognitive deficits who are clinically stable on active monitoring will be invited to participate. Patients will be randomised 1:1 to either: Intervention: rTMS Control: no rTMS Intervention The rTMS arm will undertake 12 rTMS sessions over four weeks to the frontal and parietal components of the Frontoparietal Network contralateral to the tumour. Outcomes Both groups will have the following in-person assessments at baseline, 1-month, and 3-months: Objective cognition (CANTAB and paper-based tests) Subjective cognition (FACT-Cog) Quality-of-life (EORTC-QLQ-C30) MRI scans including resting state functional MRI Changes in cognition and brain network properties over time in both groups will be compared to assess for any effects of rTMS. Anticipated impact: These projects will: Establish the utility of remote cognitive assessments in patients with brain tumours Determine the range and predictors of cognitive deficits in patients with LGG Generate an MRI map to inform our understanding of the spatial distribution of cognitive deficits Determine if rTMS changes cognitive function and the size of any effect, that could be used to power a future trial of efficacy
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