Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: Randomised controlled trial

Laboratory of Neuroscience (LIM 27) Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 - São Paulo, SP, Brazil. .
The British journal of psychiatry: the journal of mental science (Impact Factor: 7.99). 05/2011; 198(5):351-6. DOI: 10.1192/bjp.bp.110.080044
Source: PubMed


Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.
To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).
Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.
Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.
The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

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Available from: Breno Satler Diniz
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    • "Epidemiological investigations demonstrated a reduced risk of progressing to dementia among bipolar disorder patients in long-term treatment with lithium [Nunes et al. 2007]. In addition, patients with amnestic mild cognitive impairment (MCI) showed cognitive and functional stabilization with long-term treatment with lithium, also with reduced phosphorylated tau in cerebrospinal fluid, making this therapy a promising strategy [Forlenza et al. 2011]. Table 1 presents a summary of current pharmacological agents in AD. "
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    • "This observation , however, is not conclusive by itself because the cognitive measures we analyzed were neither comprehensive nor targeted for testing any specific hypothesis. Prior research has yielded mixed results (Wingo et al., 2009; Forlenza et al., 2011), calling into question the impact of lithium on cognitive function. Nonetheless, the lack of cognitive difference between Li and NoLi reduces the possibility of recall bias confounding patient reporting of prescribed medication. "
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