Could Lithium Be a Future Therapy for Dementia?
Abstract
Despite lithium’s increased potential for neurotoxicity, low doses of the medication may be safe and have cognitive benefits.
Although lithium is a well-established and highly effective treatment for patients with bipolar disorder, use of the drug has steadily declined since the early 1990s—in part due to the release of newer medications claiming less toxic profiles.
“Lithium used to be considered a medication that worsened cognition,” particularly at higher doses that increase the risk for blood toxicity, said Davangere Devanand, M.D., director of the geriatric psychiatry program at Columbia University, in an interview with Psychiatric News. “More recently there has been some preliminary evidence that low doses of lithium may have beneficial effects on cognition in patients with mild cognitive impairment and Alzheimer’s disease, though the findings are not yet consistent and have been obtained in small samples.”
To further explore whether lithium exposure is associated with a reduced risk of dementia, Davanand and colleagues from the Department of Psychiatry at Columbia University and the Ernest Mario School of Pharmacy at Rutgers University conducted a large-scale, retrospective study of patients with bipolar disorder. As the group reports in a study published last month in the British Journal of Psychiatry, lithium treatment was associated with a decreased risk for dementia in patients with bipolar disorder.
The team gathered clinical data from 27,700 Medicaid and Medicare enrollees aged 50 and older with bipolar disorder who did not receive dementia-related services in the past year. Lithium use at various doses was observed in 6,900 patients who had multiple follow-up visits within a given year.
Each visit, including the initial day of prescription, was categorized by duration of lithium exposure within that year. The categories included no exposure to lithium (0 days), sporadic exposure to lithium (1 to 60 days), intermediate exposure to lithium (61 to 300 days), and continuous exposure to lithium (301 to 365 days). Patients who used anticonvulsive therapy (20,788) as treatment for bipolar disorder were used as negative controls.
The results showed that increasing the duration of lithium exposure in the past year was associated with a gradual decrease in the incident rate for dementia; continuous exposure to lithium was statistically significant in reducing the risk of dementia by 44 percent when compared with patients in the group that had no lithium exposure. The data also showed that continuous exposure to lithium was more likely to reduce incidence of dementia than continuous exposure to anticonvulsive therapy, though it was not statistically significant.
“The results suggest that long-term lithium use may have beneficial effects on cognition and may be potentially worth testing in patients with cognitive disorders like mild cognitive impairment and Alzheimer’s disease in the future,” said Devanand.
Devanand’s group and several other groups have speculated that lithium’s cognitive protection may be linked to the drug’s ability to inhibit glycogen synthase kinase-3 (GSK-3), which causes oxidative stress and inflammation in the brain and has been implicated in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease. The researchers noted that additional studies examining the association between lithium and GSK-3 are needed to prove this hypothesis.
The study was funded by the Brain & Behavior Research Foundation and the Agency for Healthcare Research and Quality. ■
