P3‐443: Long‐term lithium treatment for patients with mild cognitive impairment: Benefits on cognition and evidence of disease modification

Two recent clinical studies in patients with Alzheimer's disease (AD) support the feasibility of trials to evaluate disease-modifying properties of lithium in older adults with dementia. This study aims to evaluate the efficacy and tolerability of long-term, low dose, lithium treatment on cognitive and biological outcomes in sample of patients at risk of dementia. 77 older adults with amnestic mild cognitive impairment (MCI) were recruited for a 12-month, randomized, placebo-controlled trial; 51 signed informed consent (6 excluded through baseline assessment); 45 subjects were randomized to receive lithium (0.25-0.5 mmol/L) (n = 24) or placebo (n = 21), and 41 reached endpoint after one year of double-blind treatment. Primary outcomes: modification of cognitive and functional scores, and/or concentrations of CSF biomarkers (Ab42, total Tau, phosphorylated Tau). Safety and tolerability of lithium treatment, and the conversion rate from MCI to AD were secondary outcomes. Patients in both groups displayed a mild progression of functional deficits as shown by the Clinical Dementia Rating Scale (Sum-of-Boxes scores). Lithium-treated patients had a better performance on tests addressing global cognitive function (ADAS-Cog) and attention tasks, as compared to controls. Lithium treatment was associated with a significant reduction in CSF concentrations of phospho-Tau (p = 0.03). Seven patients in the placebo group and 4 in the lithium group progressed from MCI to AD after one year (N.S.). Overall tolerability of lithium was good, and compliance to this study was 91%. The present data support the hypothesis that lithium has disease-modifying properties with potential clinical implications in the MCI-AD continuum.