Lithium and Alzheimer’s Disease: Neurobiological Mechanisms, Ethical Implications, and Social Perspectives on Cognitive Aging

Alzheimer’s disease is a progressive, idiopathic neurodegenerative disorder characterized by the accumulation of amyloid plaques, tau tangles, and synaptic degeneration. Its global prevalence continues to rise, posing significant challenges for healthcare systems and aging societies. Despite recent advances in disease-modifying treatment, such as monoclonal antibodies (donanemab, lecanemab, aducanumab), their high cost, limited efficacy, and risk of adverse effects underline the urgent need for therapies that are safe, effective, and economically accessible. This review evaluates the role of lithium a long-established mood stabilizer in the prevention and modulation of Alzheimer’s disease. Drawing from preclinical studies, observational data, and early-phase clinical trials published between 2017 and 2025, it examines how lithium influences key pathological mechanisms including amyloid precursor protein processing, tau phosphorylation, oxidative stress, neuroinflammation, and synaptic plasticity. Chronic exposure to low or trace doses has been associated with delayed cognitive decline and reduced disease incidence in several populations. However, evidence from randomized trials remains inconclusive, warranting further rigorous investigation. In addition to biological mechanisms, this review explores ethical and social dimensions of lithium use in older adults, including questions of informed consent, adherence, age-related pharmacokinetics, and the stigma of psychiatric medication. Lithium emerges as a biologically plausible, cost-effective, and potentially scalable strategy for addressing cognitive aging. Future directions require ethically sound, large-scale clinical trials and a broader public health dialogue on the integration of preventive pharmacotherapy into neurodegenerative disease management.