Lithium: An old drug may provide new benefits

Lithium, an anti-depressant drug that is currently used to treat mood swings and bipolar disorder, may be able to slow the progression of memory loss and cognitive decline in individuals with amnestic mild cognitive impairment (aMCI), a significant risk factor for development of Alzheimer's disease. A new study, currently in press, followed 41 individuals 60 or older with aMCI for 12 months. A total of 21 participants took low-dose lithium every day, while the other 20 received placebo. Starting with daily doses of 150 mg, regiments were then titrated to target serum levels of .25 to .5 mmol/L through weekly visits. The selected dose is lower than that commonly used for the treatment of affective disorders. Overall, the drug was well tolerated, with minimal side-effects.

Previous mouse-model studies indicate that lithium inhibits GSK3-beta, the mediator of tau phosphorylation, by decreasing the gamma-cleavage of APP, reducing both plaque formation and neurofibrillary tangles. Indeed, the current study reports a significant decrease in concentrations of phosphorylated tau (P-tau) in CSF, in turn decreasing the build up of neurofibrillary tangles. On the other hand, there was a slight, though significant, increase in P-tau observed in participants receiving placebo. Likewise, the number of conversions to AD was higher in the placebo group at 7/20, compared with the lithium group at 4/21, although the difference was not significant. After 12 months, all participants experienced a decline in memory and cognitive functioning, as indicated by the CDR. However, the decline was significantly smaller in the group treated with lithium, as indicated by the ADAS-cog and Sequence of Letters and Numbers test.

This study supports the idea that prescribing lithium to someone who is at risk for AD may have a protective effect and slow down the progression of memory loss to dementia. However, there is a need for further trails with a larger number of participants before the findings can be fully supported.