Association Between Lithium Use and Risk of Alzheimer's Disease

Objective: Current evidence for the association between use of lithium and risk of dementia is mixed. The objective of this study was to assess the risk of Alzheimer's disease associated with use of lithium. Methods: A population-based, nested case-control study was conducted using data from the National Health Insurance Research Database in 2002 covering 24.5 million beneficiaries of the Taiwan National Health Insurance Program from January 1, 1997, to December 31, 2009. A total of 2,548,625 older people were included in the study cohort. We analyzed 63,347 cases of Alzheimer's disease (ICD-9-CM codes 290.0-290.3, and 331.0) and 2 controls per case matched by age, sex, and index date (the date of the first AD claim). Conditional logistic regression was performed, adjusting for health care utilization, use of other common mood stabilizers (valproic acid and carbamazepine), hypothyroidism, type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease, epilepsy, schizophrenia, and bipolar disorder. Results: We identified 63,347 cases with Alzheimer's disease and 126,694 controls. The adjusted odds ratio (aOR) of Alzheimer's disease risk with lithium use was 1.79 (95% confidence interval [CI], 1.34-2.38) in the general population. However, when we restricted the analyses to patients with bipolar disorder to minimize potential confounding by indication, lithium was not associated with Alzheimer's disease risk (aOR = 1.36; 95% CI, 0.89-2.09), and there were no apparent trends of greater risk with increasing duration or dose. Conclusions: These findings do not support an increased or decreased risk of lithium use with Alzheimer's disease when taking into account potential confounding by indication. Further investigations of the effect of lithium with dementia need to consider the influence of confounding by indication.