¹Newcastle University, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom, ²Newcastle University, School of Psychology, Newcastle upon Tyne, United Kingdom, ³CNTW NHS Trust, Research and Development, Newcastle upon Tyne, United Kingdom, ⁴Newcastle University, Computer Science, Newcastle upon Tyne, United Kingdom

Background: Lithium is a well-established and effective medication in bipolar disorder which due to its neuroprotective effects, is now under investigation as a treatment in Alzheimer’s disease (AD). Lithium magnetic resonance imaging (⁷Li-MRI) can directly measure brain lithium concentrations in vivo, and in bipolar disorder this has shown preferential uptake to regions including the hippocampus.

Aims & Objectives: The ILiAD study was designed to determine the feasibility of using ⁷Li-MRI to measure lithium signal intensity and regional brain distribution following the lower doses of lithium used in AD.

Method: In phase I patients aged 50-80 with mild-to-moderate AD were treated with lithium carbonate MR (Priadel) at 100mg/day for 1 week and 200mg/day for 1 week with assessments at days 0, 7 and 14. Structural and 3D ⁷Li-MRI images were acquired on a 3T Philips scanner with a dual-tuned H/Li-radiofrequency coil and analysed using an in-house python-based pipeline which co-localised the anatomical and lithium images without upscaling.

Results: Interim analysis of phase I (n=3) demonstrated that the scanning protocol and low dose lithium was well tolerated, with average steady-state serum lithium levels of 0.2mmol/L and 0.3mmol/L at the 100mg/day and 200mg/day doses respectively. There was inter-subject variability in the brain lithium signal intensity which was detectable in some but not all subjects at the 200mg/day dose. These phase I results informed the decision to employ the same dosing regimen in phase II, which aims to enrol a further n=8 patients with AD alongside n=8 age-matched healthy controls.

Discussion & Conclusions: The ILiAD study has demonstrated for the first time that 3D Li-MRI signal can be detected at such low doses and blood levels of lithium. It also showed the feasibility of using this technique in a dementia population. Completion and analysis of phase II will allow comparison of brain lithium distribution in AD compared to controls and inform future clinical trials and imaging studies of lithium in dementia.