Dr. Ron’s Research Review – December 7, 2011

This week’s research review focuses on: Lithium and Alzheimer's disease

A longitudinal brain imaging study found that lithium induced an increase in gray matter volume as a neural correlate of treatment response in bipolar disorder. (Lyoo, Dager et al. 2010)

22 mood-stabilizing and antipsychotic medications-naive patients with bipolar disorder who were randomly assigned to either lithium or valproic acid (VPA) treatment after baseline assessment. Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance images revealed lithium-induced increases in gray matter volume, which peaked at week 10-12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with bipolar disorder or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained increases in cerebral gray matter volume in patients with bipolar disorder and that these changes are related to the therapeutic efficacy of lithium.

Based on that study, lithium, a simple cation, may be the "Holy Grail" for the treatment of neurodegenerative disorders. (Chuang and Manji 2007)

Continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population. (Kessing, Sondergard et al. 2008)

Dr. Ron


Articles

In search of the Holy Grail for the treatment of neurodegenerative disorders: has a simple cation been overlooked?

            (Chuang and Manji 2007) Download

Lithium treatment and risk of dementia

            (Kessing, Sondergard et al. 2008) Download

CONTEXT: It has been suggested that lithium may have neuroprotective abilities, but it is not clear whether lithium reduces the risk of dementia. OBJECTIVE: To investigate whether continued treatment with lithium reduces the risk of dementia in a nationwide study. DESIGN: An observational cohort study with linkage of registers of all patients prescribed lithium and diagnosed as having dementia in Denmark from January 1, 1995, through December 31, 2005. SETTING: We identified all patients treated with lithium in Denmark within community psychiatry, private specialist, and general practices and a random sample of 30% of the general population. Subjects A total of 16,238 persons who purchased lithium at least once and 1,487,177 persons from the general population who did not purchase lithium. Main Outcome Measure Diagnosis of dementia or Alzheimer disease during inpatient or outpatient hospital care. RESULTS: Persons who purchased lithium at least once had an increased rate of dementia compared with persons not exposed to lithium (relative risk, 1.47; 95% confidence interval, 1.22-1.76). For persons who continued to take lithium, the rate of dementia decreased to the same level as the rate for the general population. The rate of dementia decreased early after the consumption of lithium tablets corresponding to 1 prescription (typically 100 tablets) and stayed at a low level, although with a slight increase according to the number of subsequent prescriptions. The association between the number of prescriptions for lithium and dementia was unique and different from the association between the number of prescriptions for anticonvulsants and dementia. All findings were replicated in subanalyses with Alzheimer disease as the outcome. CONCLUSIONS: Continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population. Methodological reasons for this finding cannot be excluded, owing to the nonrandomized nature of data.


Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study

            (Lyoo, Dager et al. 2010) Download

Preclinical studies suggest that lithium may exert neurotrophic effects that counteract pathological processes in the brain of patients with bipolar disorder (BD). To describe and compare the course and magnitude of gray matter volume changes in patients with BD who are treated with lithium or valproic acid (VPA) compared to healthy comparison subjects, and to assess clinical relationships to gray matter volume changes induced by lithium in patients with BD, we conducted longitudinal brain imaging and clinical evaluations of treatment response in 22 mood-stabilizing and antipsychotic medications-naive patients with BD who were randomly assigned to either lithium or VPA treatment after baseline assessment. Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance images revealed lithium-induced increases in gray matter volume, which peaked at week 10-12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with BD or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained increases in cerebral gray matter volume in patients with BD and that these changes are related to the therapeutic efficacy of lithium.


References

Chuang, D. M. and H. K. Manji (2007). "In search of the Holy Grail for the treatment of neurodegenerative disorders: has a simple cation been overlooked?" Biol Psychiatry 62(1): 4-6.

Kessing, L. V., L. Sondergard, et al. (2008). "Lithium treatment and risk of dementia." Arch Gen Psychiatry 65(11): 1331-5.

Lyoo, I. K., S. R. Dager, et al. (2010). "Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study." Neuropsychopharmacology 35(8): 1743-50.