P2‐526: Renal function outcome after lithium therapy for cognitive decline

Experimental studies conducted in neuronal culture and animal models provide evidence of the neurotrophic and neuroprotective properties of lithium, with alleged impact on the management of certain neurodegenerative conditions, namely Alzheimer's disease (AD). Recent clinical trials support the feasibility and the potential benefits of this approach. However, chronic lithium use is associated with clinically relevant adverse effects, particularly renal dysfunction. To evaluate long-term safety of lithium therapy on parameters of renal function of elderly patients with mild cognitive impairment (MCI). Subjects included in this study are participants of a randomized clinical trial with lithium addressing disease-modification in the MCI-AD continuum. Study design: double blind, placebo controlled trial of lithium (N = 22) versus placebo (N = 22) for the treatment of patients with MCI for three years. Identical tablets holding 150, 300, 450 and 600 mg of lithium carbonate or placebo were administered orally (b.i.d.). Lithium doses were adjusted to keep serum levels between 0.2 and 0.5mEq/L. Safety and tolerability of treatments were longitudinally evaluated at three-month intervals by clinical examination, scores on the UKU side-effect scale, and laboratory tests addressing renal function (and other parameters not included in the present assessment). Statistical analysis was performed with SPSS 18. Baseline serum concentrations of creatinine were not significantly different between the two groups at baseline (lithium, 0.84 ± 0.20; placebo, 0.87 ± 0.23; p = 0.76), nor at the endpoint of three years (lithium, 0.93 ± 0.27; placebo, 0.96 ± 0.38; p = 0.19). Kaplan-Meyer curves did not indicate significant changes in renal function according to treatment groups over time (p = 0.31); intra-group comparisons (p = 0.94) indicated long-term stability of such parameters upon follow-up. Low-dose, chronic lithium therapy appears to be clinically safe and not associated with significant changes in renal function in older adults with MCI. The present findings support the use of lithium salts as a candidate drug for disease-modification in AD.