People with bipolar may be getting a bonus on lithium
STUDY: Weckstein AR et al, medRxiv 2026, 13:2026.01.12.26343472.
STUDY TYPE: Retrospective cohort study (target trial emulation)
EVIDENCE GRADE: Low (5/10)
FUNDING: National Institutes of Health; German Heart Foundation
Background
Lithium has more neuroprotective mechanisms than any psych med, and some of those are relevant to dementia. It inhibits GSK-3β, a kinase involved in tau phosphorylation, and reduces amyloid deposition in animal models. This large study asks whether it can slow cognitive decline.
The Study
Using Medicare claims (2013–2022), researchers identified 9,461 adults aged 55 and older with both bipolar disorder and early cognitive impairment — essentially, patients at risk for dementia. They compared those newly starting lithium (n = 1,133) against those starting antiepileptic mood stabilizers like valproate or lamotrigine (n = 8,328), following them for up to five years. The active comparator design is a strength: both groups were being treated for the same condition, reducing confounding by indication.
Lithium initiators had a 13% lower 5-year risk of progressing to advanced dementia (risk ratio 0.87) and a 25% lower risk of a long-term care stay with dementia (risk ratio 0.75). Effects were strongest in patients who already had cognitive impairment or mild-to-moderate Alzheimer’s at baseline. Findings were replicated in two additional commercial insurance databases.
Limitation: This is observational data — residual confounding can’t be ruled out. But the sample is large, the methodology is rigorous, and the replication across three databases is reassuring.
Practice Implications
- This kind of data is not a justification to start lithium in those who don’t already need it, but older adults with mood disorders who are taking lithium will appreciate hearing about this added benefit.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- Are you skeptical? Or do you think lithium prevents cognitive decline?
