Does Lithium Use Decrease Alzheimer’s Risk?

Bipolar patients' brain cells predict response to lithium
Bipolar patients’ brain cells predict response to lithium
Researchers found that valproic acid increased the risk of Alzheimer's disease.

Lithium use neither increases nor decreases the risk of the development of Alzheimer’s disease (AD), according to a study conducted by a joint team of researchers affiliated with Johns Hopkins Bloomberg School of Public Health and several universities in Taiwan.

The population-based, nested case-control study, which was published in the December 20, 2016 issue of the Journal of Clinical Psychiatry, used data from a Taiwan database that included 2,548,625 people (65 years of age and older). The researchers analyzed 63,347 cases of AD and 2 controls per case (n = 126,694) matched by age, sex, and index date (ie, the date of the first AD claim). The researchers used conditional logistic regression to adjust for healthcare utilization, use of other mood stabilizers (valproic acid and carbamazepine), hypothyroidism, type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease, epilepsy, and bipolar disorder (BD). The mean age of the study cohort was 82.5 years (SD 5.5). The study was undertaken because previous literature investigating the relationship between lithium use and the risk of dementia has yielded mixed results.

A total of 4.5% of patients with BP and dementia had a history of lithium use compared with 2.2% of patients with BD and without dementia. The researchers found that the adjusted odds ratio (aOR) of AD risk with lithium use was 1.79 (95% CI, 1.34-2.38) in the general population. However, when the analysis was restricted to patients with BD, to avoid potential confounding by indication, lithium was found not to be associated with AD risk (aOR = 1.36; 95% CI, 0.89-2.09). The risk of AD increased with increased cumulative duration of lithium exposure and mean daily dose, but after full adjustment, these trends were no longer apparent.

Of note, valproic acid — a mood stabilizer commonly used to treat BD — was found to increase AD risk, prompting the researchers to recommend “further studies to determine if the prescription of valproic acid for the treatment of BD in the elderly is contraindicated, due to increasing concerns of increasing cognitive complications.”  

In an interview with Psychiatry Advisor, G. Caleb Alexander, MD, co-Director, Johns Hopkins Center for Drug Safety and Effectiveness and a study coauthor, commented, “The question of whether lithium is associated with dementia is a complicated one to answer, and many prior studies have been limited by small sample sizes, poorly defined outcomes, and short follow-up periods.”

“Our study is important because of how commonly lithium is used and continued uncertainty regarding its potential association with dementia,” he said. “As with all drugs, lithium has risks and benefits that have to be balanced for specific patients.” But, “…while there may be many reasons not to use lithium in a particular patient, we did not find any association between lithium use and subsequent dementia in this study.”

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Cheng C, Zandi P, Stuart E, et al. Association between lithium use and risk of Alzheimer’s disease [published online December 20, 2016]. J Clin Psychiatry. doi: 10.4088/JCP.15m10304