In their recent comprehensive review of the literature on the putative cognitive enhancement properties of lithium, Tsaltas and colleagues (2009) stated that “recent clinical studies show results promising of a beneficial impact of lithium on cognition in patients with dementia (Terao et al. 2006; Nunes et al. 2007; Engel et al. 2006).” However, only two of the three studies cited by Tsaltas et al. were in humans. More importantly, none specifically examined the cognitive effects of lithium in patients with Alzheimer’s disease (AD), a disorder in which preclinical data indicate this agent may exert potentially diseasemodifying effects (Engel et al. 2006; Caccamo et al. 2007). We previously conducted a pilot study (Brinkman et al. 1984) to investigate the relationship between lithiuminduced elevation in red blood cell (RBC) choline and memory in 14 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, third edition diagnosis of primary degenerative dementia (Alzheimer-type senile dementia). Diagnoses were established after complete medical, neurological, neuropsychological, and psychiatric evaluations and routine laboratory tests. Following work up, single-blind lithium carbonate treatment was started at a dose of 150 mg/day and gradually increased during 6 weeks of treatment. A comprehensive cognitive battery including measures of working memory was administered weekly.

Plasma lithium was maintained at low concentrations (0.46. 0.60 meq/l). Despite this, five patients developed side effects, especially extrapyramidal symptoms, which interfered with memory testing and resulted in exclusion of these patients from data analysis. Even though significant elevations in RBC choline levels were observed, lithium treatment did not result in any significant improvement on any of the cognitive measures in the remaining patients who experienced no signs of neurotoxicity. The absence of significant cognitive enhancing effects of lithium treatment in AD patients is consistent with the findings from a recent report (Macdonald et al. 2008) in which open label treatment for up to 1 year produced no significant improvement on the Mini-mental State Examination in elderly individuals with mild to moderate AD (N= 22). This study was also characterized by a high attrition rate since only eight patients were still taking lithium at 1 year though discontinuation was ascribed to possible side effects in only three patients.