Lithium appears to have potentially meaningful neuroprotective effects and may lower dementia risk or slow cognitive decline, but evidence is still limited and heterogeneous, and it is not a standard, guideline‑endorsed dementia prevention or treatment strategy outside research settings. Benefits have been reported at both therapeutic and “microdose” levels, but safety, optimal dosing, and patient selection remain unresolved, so any use should be under medical supervision, especially given renal and thyroid toxicity risks at higher doses.

Epidemiologic and clinical outcome data

Several observational studies and meta‑analyses suggest that people treated with lithium have a lower incidence of dementia and Alzheimer’s disease (AD), especially with longer treatment duration. A 2024 systematic review of seven studies reported relative risk reductions of about 34–41% for AD and dementia among lithium‑treated patients, with some indication that longer exposure (>5 years) confers greater protection.

Low‑dose and microdose RCTs in MCI or early AD have shown stabilization or slower decline on cognitive measures over 15–24 months, although sample sizes are small. In bipolar or mood‑disorder cohorts, long‑term lithium maintenance has repeatedly been associated with a lower prevalence of dementia compared with similar patients not receiving lithium, again suggesting a protective signal but not definitive proof.

Microdose and low‑dose lithium

A 2013 randomized trial in AD patients found that 300 μg/day (microgram, not milligram) lithium given for 15 months prevented the MMSE decline seen in the placebo group, implying disease‑modifying potential at extremely low doses with minimal toxicity. A research summary from the Alzheimer’s Drug Discovery Foundation notes that microdose lithium (≤5 mg/day elemental) appears safe and in that small trial slowed cognitive decline, but emphasizes that evidence is preliminary and larger trials are needed.

Other low‑dose trials (e.g., 150–600 mg lithium carbonate targeting subtherapeutic serum levels) in amnestic MCI have shown stabilization or modest improvement in cognitive performance over roughly 2 years, again with relatively good tolerability, but not yet enough to change practice guidelines. Ongoing and planned trials are testing trace‑dose lithium (e.g., 50 mg/day salt in people at risk of MCI) and titrated low‑level lithium in elders with MCI to better define benefit–risk.

Proposed mechanisms of benefit

Preclinical work indicates that lithium inhibits glycogen synthase kinase‑3β (GSK‑3β), which reduces tau hyperphosphorylation and shifts APP processing away from amyloidogenic pathways, lowering amyloid‑β and tau pathology in AD models. Lithium also enhances autophagy and neurogenesis, supports synaptic plasticity, reduces oxidative stress and neuroinflammation, and helps maintain mitochondrial and calcium homeostasis, all of which are relevant to neurodegeneration.

Animal models show that chronic lithium treatment reduces amyloid plaques and neurofibrillary tangles, preserves hippocampal neurons, and improves memory performance, supporting a genuine disease‑modifying effect rather than purely symptomatic benefit. Recent human neuropathology work suggests that lithium depletion in the prefrontal cortex may be an early event in AD, and restoration of low‑level lithium in mouse models reversed memory loss and prevented age‑related cognitive decline, further supporting a causal role.

Lithium in drinking water and population data

Ecological and cohort studies have observed that regions or municipalities with higher trace lithium levels in drinking water have lower dementia incidence rates, even though absolute concentrations are far below psychiatric dosing levels. While such data are vulnerable to confounding, they align with microdose RCT findings and suggest that chronically low environmental lithium exposure might exert a subtle protective effect on brain aging.

However, not all epidemiologic data agree; some analyses show benefit only at shorter or very long exposure durations, and others have reported neutral or even adverse associations, underscoring the need for cautious interpretation. Meta‑analyses generally find a protective association overall but highlight heterogeneity in study design, populations, and dosing, so causality remains unproven.

Practical considerations and risks

At therapeutic doses used for bipolar disorder, lithium carries well‑known risks including chronic kidney disease, nephrogenic diabetes insipidus, hypothyroidism, weight gain, and potential toxicity with drug interactions (e.g., NSAIDs, ACE inhibitors, diuretics). Even low‑dose strategies require monitoring of renal and thyroid function, especially in older adults who are already at increased risk for CKD and polypharmacy interactions.pmc.ncbi.nlm.nih+1

At microdose levels (≤300 μg/day), reported trials have not shown significant safety issues to date, but long‑term safety data in large populations are lacking, and such preparations are not standardized or regulated for dementia prevention. Current expert reviews conclude that lithium is a promising candidate for dementia prevention or early‑stage disease modification, but until larger, well‑controlled trials report, it should be considered investigational rather than a routine preventive supplement for cognitive decline.

Forlenza, Orestes V., et al. “Disease-Modifying Properties of Long-Term Lithium Treatment for Amnestic Mild Cognitive Impairment: Randomised Controlled Trial.” British Journal of Psychiatry, vol. 198, no. 5, 2011, pp. 351–56, doi:10.1192/bjp.bp.110.080044.

Baethge, Christopher. “Low-Dose Lithium against Dementia.” International Journal of Bipolar Disorders, vol. 8, no. 1, 2020, p. 25, doi:10.1186/s40345-020-00188-z.

Forlenza, Orestes V., et al. “Clinical and Biological Effects of Long-Term Lithium Treatment in Older Adults with Amnestic Mild Cognitive Impairment: Randomised Clinical Trial.” British Journal of Psychiatry, vol. 215, no. 5, 2019, pp. 668–74, doi:10.1192/bjp.2019.76.