Though no clinical benefit of lithium has been demonstrated in completed clinical trials, it was argued that target engagement was not established, and a Phase 2 trial was initiated under the hypothesis that replicating the positive effect seen in epidemiological data may require longer treatment and initiation earlier in the disease process. Thus, 80 patients with mild cognitive impairment (MCI) are undergoing treatment with lithium for two years, with progression assessed using cognitive testing, CSF biomarkers (GSK3β, ptau), and brain atrophy via 7 T MRI (NCT03185208). Another ongoing trial is assessing the effect of lithium on agitation and aggression in 60 patients with bvFTD (NCT02862210), though the mechanism of this effect is not necessarily tau-mediated.
