Can Lithium Diminish Cognitive Decline in People with Dementia?
by Umar Iqbal, MBBS, Uzma Qayyum, MBBS, Muhammad Waqas, MD & Steven Lippmann, MD
Lithium is known for its role in the treatment of patients with bipolar disorder. Recently, lithium has been documented to slow cognitive decline and the development of dementias. Lithium may have neuroprotective importance with the increasingly aging population and higher incidence of dementia nowadays. This review summarizes the findings about this topic and their biological plausibility; the clinical efficacy of lithium in these cases is under discussion.
This neuroprotective mechanism involves inhibition of glycogen synthase kinase-3 to reduce beta-amyloid deposition and tau phosphorylation. It may explain the presumptive pathognomonic finding in Alzheimer’ s disease. It also leads to increased brain-derived neurotrophic factor expression, crucial for neuron survival, growth and plasticity. It boosts learning, memory and high-level thinking by supporting synapse formation. 1, 2
Lithium was reported to improve performance and prevent dementia. 3 Cerebral spinal fluid concentrations of tau were diminished by lithium pharmacotherapy. This result was countered by other investigators, 4 but it stimulated further research. One meta-analysis of randomized controlled trials evidenced no consistent cognitive improvement. 5 Most of its benefits were preventative rather than therapeutic.
There is study support for lithium’ s role in lowering the risk of dementia( hazard ratio [ HR ] 0.56), including subjects with Alzheimer’ s Disease( HR of 0.55) and / or vascular dementias( HR of 0.36). 6 Bipolar affective disorder is a risk factor for dementia, and a lithium regimen yields a lower incidence of dementia as compared to the general population.
There is an association between trace lithium in water supplies and a lower incidence and / or mortality from dementias. This occurred with concentrations as low as 0.002 mg / L. 7. Testing by the Louisville Water Company last showed lithium levels below 9 micrograms per liter, so it is possible that our water has very tiny amounts – bonus!
Despite these promising findings, evidence remains limited and inconsistent, particularly regarding its therapeutic benefits and the minimum effective dose required. Therapies for our aging population mandate further investigation. Ultimately, lithium’ s potential extends beyond its traditional psychiatric use, and exploring its full role in dementia care will depend on sustained research efforts.
References
1
Gildengers AG, Ibrahim TS, Anderson SJ, et al. Low-dose lithium for mild cognitive impairment: a pilot randomized clinical trial. JAMA Neurol. Published March 2, 2026. doi: 10.1001 / jamaneurol. 2026.0072. Accessed June 02, 2026.
2
Xiao K, Sayed H, Xing J, et al. The effects of lithium on beta-amyloid deposition and tau phosphorylation: a systematic review. J Affect Disord. 2026 Feb 15; 395( Pt A): 120721. doi: 10.1016 / j. jad. 2025.120721. Epub 2025 Nov 17. PMID: 41260370. Accessed June 08, 2026.
3
Forlenza OV, Diniz BS, Radanovic M, et al. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011 May; 198( 5): 351-356. doi: 10.1192 / bjp. bp. 110.080044. PMID: 21525519. Accessed May 31, 2026.
4
Baethge C. Low-dose lithium against dementia. Int J Bipolar Disord. 2020 Aug 3; 8( 1): 25. doi: 10.1186 / s40345-020-00188-z. PMID: 32743689; PMCID: PMC7396410. Accessed June 03, 2026.
5
Pereira da Silva AM, de Deus O, Ribeiro FV, et al. Efficacy and safety of lithium for behavioral and cognitive symptoms in Alzheimer’ s disease dementia: a systematic review with frequentist and Bayesian meta-analysis. Am J Geriatr Psychiatry. 2026 Mar; 34( 3): 371-385. doi: 10.1016 / j. jagp. 2025.10.001. Epub 2025 Oct 4. PMID: 41177743. Accessed June 06, 2026.
6
Chen S, Underwood BR, Jones PB, et al. Association between lithium use and the incidence of dementia and its subtypes: a retrospective cohort study. PLoS Med. 2022 Mar 17; 19( 3): e1003941. Accessed June 06, 2026. doi: 10.1371 / journal. pmed. 1003941. PMID: 35298477; PMCID: PMC8929585.
7
Fraiha-Pegado J, de Paula VJR, Alotaibi T, et al. Trace lithium levels in drinking water and risk of dementia: a systematic review. Int J Bipolar Disord. 2024 Aug 30; 12( 1): 32. doi: 10.1186 / s40345-024-00348-5. PMID: 39212809; PMCID: PMC11364728. June 09, 2026
Umar Iqbal is a current infectious disease UofL research physician, applying for psychiatry residency in 2027.( non-member)
Uzma Qayyum is a current infectious disease UofL research physician, applying for psychiatry residency in 2027.( non-member)
Dr. Waqas, is an infectious disease UofL research physician, who just matched into family medicine residency at the University of Georgia.( non-member)
Dr. Lippman is an emeritus professor of psychiatry at UofL and currently practices primary care medicine at Louisville’ s Family Community Clinic.
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