Tags

Type your tag names separated by a space and hit enter

Does lithium prevent Alzheimer's disease?
Drugs Aging. 2012 May 01; 29(5):335-42.DA

Abstract

Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.

Authors+Show Affiliations

Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil. forlenza@usp.brNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22500970

Citation

Forlenza, Orestes V., et al. "Does Lithium Prevent Alzheimer's Disease?" Drugs & Aging, vol. 29, no. 5, 2012, pp. 335-42.
Forlenza OV, de Paula VJ, Machado-Vieira R, et al. Does lithium prevent Alzheimer's disease? Drugs Aging. 2012;29(5):335-42.
Forlenza, O. V., de Paula, V. J., Machado-Vieira, R., Diniz, B. S., & Gattaz, W. F. (2012). Does lithium prevent Alzheimer's disease? Drugs & Aging, 29(5), 335-42. https://doi.org/10.2165/11599180-000000000-00000
Forlenza OV, et al. Does Lithium Prevent Alzheimer's Disease. Drugs Aging. 2012 May 1;29(5):335-42. PubMed PMID: 22500970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Does lithium prevent Alzheimer's disease? AU - Forlenza,Orestes V, AU - de Paula,Vanessa J, AU - Machado-Vieira,Rodrigo, AU - Diniz,Breno S, AU - Gattaz,Wagner F, PY - 2012/4/17/entrez PY - 2012/4/17/pubmed PY - 2012/8/16/medline SP - 335 EP - 42 JF - Drugs & aging JO - Drugs Aging VL - 29 IS - 5 N2 - Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly. SN - 1179-1969 UR - https://www.unboundmedicine.com/medline/citation/22500970/Does_lithium_prevent_Alzheimer's_disease L2 - https://dx.doi.org/10.2165/11599180-000000000-00000 DB - PRIME DP - Unbound Medicine ER -