Lithium
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Laboratory and animal studies suggest lithium could protect the brain from cognitive decline and Alzheimer's disease, but results from human trials have been mixed. To clarify the picture, researchers combined data from multiple clinical trials to test whether pharmaceutical lithium salts have meaningful benefits for brain health.
The authors systematically reviewed and meta-analyzed six randomized, placebo-controlled trials (435 participants) that compared lithium supplementation with placebo for roughly 10 weeks to 24 months. All participants had either mild cognitive impairment, stage of measurable decline that can precede dementia, or diagnosed Alzheimer's disease. The main outcome was change in cognition, prioritizing the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), with the Mini-Mental State Examination (MMSE) used when needed. The tested lithium salts were: lithium carbonate, lithium sulfate, and lithium gluconate.
- When results from all six trials were combined, lithium did not lead to better overall cognitive outcomes than placebo.
- In the primary analysis using the most detailed cognitive test (ADAS-Cog), the average difference between lithium and placebo was small and could not be confidently attributed to the treatment rather than chance.
- Follow-up analyses that relied on different cognitive measures or prioritized different tests reached the same conclusion and showed no consistent cognitive benefit from lithium.
- Measures of behavioral and psychological symptoms of dementia, such as agitation or mood changes, were similar between lithium and placebo groups.
- Subgroup analyses found no consistent benefit based on diagnosis (mild cognitive impairment versus Alzheimer's disease), study length, lithium dose, or lithium salt type.
- One small study suggested a stronger effect from lithium, but it was judged high risk for bias, making its result unreliable.
Lithium's biological effects may depend strongly on its chemical form and how it behaves in the brain. Studies in animals show that lithium can stick to amyloid-β, the protein that forms plaques in Alzheimer's disease. When this happens, lithium becomes trapped inside plaques instead of remaining available to brain cells, where it could help regulate inflammation, communication between neurons, and limiting harmful changes to tau, a structural protein that helps stabilize neurons. Commonly tested lithium forms, especially lithium carbonate, appear more likely to bind to amyloid plaques in this way. By contrast, laboratory and animal studies suggest that lithium orotate, a different chemical form, may enter brain cells more easily and avoid plaque binding.
Importantly, the clinical trials analyzed here did not test lithium orotate, only carbonate, sulfate, and gluconate. As a result, the study supports the conclusion that standard lithium supplements do not slow cognitive decline in people with mild cognitive impairment or Alzheimer's disease, while leaving open the possibility that other lithium formulations could be more effective. In Q&A #69, I discuss the benefits and risks of low-dose lithium supplementation.
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Lithium blocks some of the sleep disturbances, memory loss, and learning problems tied to fetal alcohol syndrome in mouse study www.sciencedaily.com
From the article:
The new study found that giving the drug to newborn mice 15 minutes after “binge” alcohol consumption eliminated the hyperactivity and sleep deficits seen when rodents exposed to alcohol became adults. Moreover, the researchers report, lithium chloride-treated mice were much less likely to show the 25 percent drop in memory and cognitive test scores seen in untreated mice given the same amount of alcohol.
“Our study showed that lithium chloride prevented many of the damaging neurological effects of alcohol abuse on the still-developing brain, especially the impact on the parts of the brain controlling sleep,” says co-senior study investigator Donald Wilson, PhD.
Promoting BDNF as one pathway to brain cell survival:
“Lithium chloride is known to block many pathways that lead to brain cell death, while promoting others that lead to survival, like brain-derived neurotrophic factor, or BDNF,” says Saito, a research assistant professor at NYU Langone. Further experiments are needed, she says, to determine if chemicals that stimulate BDNF production also blunt the effects of alcohol abuse in newborn mammals.