© 2007 The Royal College of Psychiatrists
Correspondence |
Lithium for prevention of Alzheimer’s disease
Oita University Faculty of Medicine, Oita, Japan. Email: terao{at}med.oita-u.ac.jp
EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL
Nunes et al (2007) reported that the prevalence of Alzheimer’s disease in a group of elderly patients with bipolar disorder who were on continuous lithium treatment was significantly less than in a similar group without recent lithium therapy. After controlling for age, lithium use remained associated with a smaller risk of Alzheimer’s disease (age-adjusted OR=0.079, 95% CI 0.020–0.321). Conversely, Dunn et al (2005) showed that patients who received lithium had a significantly higher risk of dementia than those who did not (age-adjusted OR=1.8, 95% CI 1.1–2.8).
Nunes et al (2007) found no differences between the lithium and the comparison group in neuropsychological performance after excluding patients with Alzheimer’s disease. This is in accordance with our study using Mini-Mental State Examination (MMSE) scores (Terao et al, 2006). Our study, however, showed that patients with present and/or past history of lithium treatment had significantly better MMSE scores than patients without any history of lithium treatment (Terao et al, 2006). It is important to further investigate lithium in the prevention of Alzheimer’s dementia with a large number of patients in prospective studies.
If lithium has a preventive effect for Alzheimer’s disease, there may be two possible mechanisms. First, it might indirectly prevent dementia via its prophylactic effects on mood disorders, because the rate of dementia increased 13% with every episode leading to admission for patients with depressive disorder and 6% for patients with bipolar disorder, when adjusted for differences in age and gender (Kessing & Andersen, 2004). Second, lithium might directly prevent dementia via its inhibition of glycogen synthase kinase 3 (GSK-3) alpha (Phiel et al, 2003) and GSK-3 beta (Phiel & Klein, 2001). Although Nunes et al (2007) found no significant differences in the number of previous depressive and manic episodes between the lithium and comparison groups, at present both possibilities should be borne in mind.
REFERENCES
- Dunn, N., Holmes, C. & Mullee, M. (2005) Does lithium therapy protect against the onset of dementia? Alzheimer Disease and Associated Disorders, 19, 20 –22.[CrossRef][Medline]
- Kessing, L. V. & Andersen, P. K. (2004)
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[Abstract/Free Full Text] - Nunes, P. V., Forlenza, O. V. & Gattaz, W. F.
(2007) Lithium and risk for Alzheimer’s disease in
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[Abstract/Free Full Text] - Phiel, C. J. & Klein, P. S. (2001) Molecular targets of lithium action. Annual Review of Pharmacology and Toxicology, 41, 789 –813.[CrossRef][Medline]
- Phiel, C. J., Wilson, C. A., Lee, V. M.-Y., et al (2003) GSK-3 alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature, 423, 435 –439.[CrossRef][Medline]
- Terao, T., Nakano, H., Inoue, Y., et al (2006) Lithium and dementia: a preliminary study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 30, 1125 –1128.[CrossRef][Medline]
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