A Daily Small Dose Of Lithium May Prevent Progression of Mild Cognitive Impairment

January 6, 2012 · Posted in Potential Treatments 

lithiumA very small dose of lithium, 150 mg/day, has been reported to lessen the progression of mild cognitive impairment over a period of one year compared to placebo. In a 2011 article by Orestes Forlenza and colleagues published in the British Journal of Psychiatry, the researchers reported the findings from their prospective randomized study of lithium versus placebo in 45 patients.

Editor’s Note: While these findings must still be replicated, there are several reasons to suggest that they may be reliable and valid.

A preliminary epidemiological study by Lars Kessing et al. published in the Archives of General Psychiatry in 2008 indicated that risk of dementia was lower in patients taking lithium chronically, who were identified by having renewed their prescriptions at least once.

Lithium exerts a number of neuroprotective effects in animals. These effects include increases in cell survival factors BDNF and BCl-2 and decreases in cell death factors BAX and P53.  Lithium can also decrease the size of a brain lesion and its associated functional deficits in many animal models of neuropsychiatric disorders, including stroke, Huntington’s chorea, Alzheimer’s disease, and AIDS (according to the work of DeMaw Chuang and colleagues who formerly worked in this editor Robert Post’s laboratory at the National Institute of Mental Health).  

In humans lithium increases neuronal integrity, as observed via magnetic resonance spectroscopy (MRS) measuring increases in N-acetylaspartate (NAA). Lithium also increases gray matter volume and hippocampal volume measured via magnetic resonance imaging (MRI).  

Miniscule amounts of lithium may exert positive effects in humans. Three studies (carried out in Texas and in regions of Japan and Austria) have found that higher trace levels of lithium in the water supply, which are still approximately 1000-fold lower than those considered necessary for therapeutic effects in bipolar disorder, are associated with a reduced suicide rate in the general population compared to nearby areas with lower trace levels of lithium in the water.

While it will take time to establish the possible effects of lithium on long-term cognition, this editor suggests that quicker action be considered for patients with bipolar illness and mild cognitive impairment who are not currently taking lithium. Perhaps they should talk to their physicians about adding lithium in low to moderate doses to their therapeutic regimen.

There are several rationales for considering this option.

1. Even euthymic patients have been shown to have some cognitive deficits compared to volunteer controls. These deficits increase in likelihood with the number of affective episodes experienced.

2. Depression is a risk factor for the progression of mild cognitive impairment to full-blown cognitive dysfunction, and lithium can help treat and prevent depressions.

3. The experience of four depressive episodes (unipolar or bipolar) doubles the risk for the diagnosis of dementia late in life.

4. Given that depression is the most difficult phase of bipolar disorder to treat and prevent, patients with the disorder are at high risk for further episodes and the subsequent increased risk for cognitive dysfunction.

5.  Although very low-dose lithium has never been studied in patients with bipolar disorder, it is possible that treatment with moderate doses could decrease risk of suicide, given the data from the three studies showing positive effects on suicide in the general population based on higher trace levels of lithium in the water supply. Parenthetically, people living in areas with higher trace levels also lived longer than those living in areas with lower trace levels.

6.  The side effects of 150mg lithium in the study by Forlenza did not differ from that of placebo.

Thus, there might be some rationale for a patient with bipolar disorder who has neither kidney dysfunction nor an allergy or intolerance to lithium to be prescribed a small dose of lithium even if it has not proven to be an effective treatment for that patient’s mood disorder.

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