Daily lithium carbonate showed promise in the LATTICE pilot study in older adults with mild cognitive impairment.[1] However, the study did not meet the pre-specified significance threshold for any of the six co-primary outcomes compared.[1] Previous research has demonstrated lithium's neuroprotective effect on the brain.[1] A new study shows that the loss of endogenous lithium in the brain may be an early warning sign of Alzheimer's disease.[1] Depletion of endogenous cortical lithium by approximately 50 percent resulted in increased amyloid beta deposition, accumulation of phospho-tau protein, proinflammatory activation of microglia, loss of synapses, axons, and myelin, and accelerated cognitive decline.[1] These findings reveal the physiological effects of endogenous lithium in the brain and suggest that disruption of its homeostasis may be an early event in the pathogenesis of Alzheimer's disease.[1] Lithium substitution with amyloid-avoiding salts is a potential approach to prevention and treatment.[1]