In Lancet 2000, it was found that there could be a 3% increase in grey matter with 1 month of of lithium therapy. Sadly, it is not that easy. Some say it would take 300+ mg/day to do anything though one study suggests Alzheimer’s protection at 0.3 mg(300 micrograms)/day.
Moore, G. J., Bebchuk, J. M., Wilds, I. B., Chen, G., & Menji, H. K. (2000).
Lithium-induced increase in human brain grey matter.
Lancet. 2000 Oct 7;356(9237):1241-2.
Lithium-induced increase in human brain grey matter.
Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK.
http://www.ncbi.nlm.nih.gov/pubmed/11072948
found 3% gray matter increases over 1 month.
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This was confirmed by another study:
Brambilla, P., Stanley, J. A., Sassi, R. B., Nicoletti, M. A., Mallinger, A. G., Keshavan, M. S., Soares, J. C. (2004).
1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration.
Neuropsychopharmacology, 29(10), 1918-1924.
http://brain.med.wayne.edu/pdfs/hmrs_study.pdf
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One study measured N-acetyl-aspartate which is a “putative marker of neuronal viability and function.” It was increased with lithium supplementation.
Biol Psychiatry. 2000 Jul 1;48(1):1-8.
Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects?
Moore GJ, Bebchuk JM, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds IB, Faulk MW,
Koch S, Glitz DA, Jolkovsky L, Manji HK.
http://www.ncbi.nlm.nih.gov/pubmed/10913502
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One study did not find total gray matter changed in healthy subjects on lithium, but there appeared to be more in the dorsal lateral prefrontal cortex (mood regulation), and the anterior cingulate cortex (reward anticipation, decision-making, empathy, impulse control, and emotion – also part of the chronic pain network). However, they were still getting “low therapeutic” blood levels – 0.34 -0.67 mmol/l. They started with 300 mg – worked up to 600 mg and then adjusted things to keep a 0.6 mmol/l blood level. Oddly, they found a 2% increase in white matter.
Monkul, E. Serap, Koji Matsuo, Mark A. Nicoletti, Nicole Dierschke, John P. Hatch, Manish Dalwani, Paolo Brambilla et al.
Prefrontal gray matter increases in healthy individuals after lithium treatment: a voxel-based morphometry study.
Neuroscience letters 429, no. 1 (2007): 7-11.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693231/
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There is a catch:
One study in healthy subjects- albeit for 11 days, suggested that “volume changes” were being misinterpreted:”Magnetic resonance images of the brain differ before and after lithium, but this difference might derive from a change in the characteristics of the signal rather than a tangible increase in volume”.
Cousins, David A., Benjamin Aribisala, I. Nicol Ferrier, and Andrew M. Blamire.
“Lithium, gray matter, and magnetic resonance imaging signal.”
Biological psychiatry (2012).
http://www.biologicalpsychiatryjournal.com/articleS0006-3223%2812%2900856-6/abstract
Secondly, part of the increased volume is fluid retention:
Animal studies demonstrate lithium induces 3.1% brain fluid retention – exactly the brain increase and a more likely cause of 3% increase in gray matter.
Psychopharmacology (Berl). 2006 May;186(1):41-7. Epub 2006 Mar 30.
Lithium and inositol: effects on brain water homeostasis in the rat.
Phatak P, Shaldivin A, King LS, Shapiro P, Regenold WT.
http://www.ncbi.nlm.nih.gov/pubmed/16572264/
Another problem is the dosage issues:
The first study’s approach was and I will quote:”4 weeks of masked lithium treatment given at doses that produced therapeutic concentrations (about 0·8 mmol/L)” – to achieve those blood levels would require 900-1200 mg lithium carbonate a day – which is too much for most of my patients to tolerate.
Are these therapeutic levels needed? – a tissue culture study of nerves was done:
Chuang, D. M., Chen, R. W., Chalecka‐Franaszek, E., Ren, M., Hashimoto, R., Senatorov, V., … & Leeds, P. (2002).
Neuroprotective effects of lithium in cultured cells and animal models of diseases.
Bipolar disorders, 4(2), 129-136.
http://www.ncbi.nlm.nih.gov/pubmed/12071510
they stated “The lithium neuroprotection against glutamate excitotoxiciy is long-lasting, requires long-term pretreatment and occurs at therapeutic concentrations of this drug.”
There was a “subtherapeutic” study done to prevent Alzheimer’s disease:
Forlenza, Orestes V., Breno S. Diniz, Márcia Radanovic, Franklin S. Santos, Leda L. Talib, and Wagner F. Gattaz.
“Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial.”
The British Journal of Psychiatry 198, no. 5 (2011): 351-356
http://bjp.rcpsych.org/content/198/5/351.full
- single-centre, randomised, double-blind, placebo-controlled study
- starting at 150 mg lithium titrated up until blood levels of 0.25-0.5 mmol/l which could take 300 – 600 mg/day
- In amnesic (memory) cognitive dysfunction – no statistical difference in conversion to alzheimer’s disease over 1 yr. but some soft signs of improved cognitive function and significant reductions of Tau proteins
Attempts to use lithium at therapeutic levels to prevent progression of dementia has been difficult because of high dropout rates. (only 8/25 lasted 1 year)
Macdonald A, Briggs K, Poppe M, Higgins A, Velayudhan L, Lovestone S.
A feasibility and tolerability study of lithium in Alzheimer’s disease.
Int J Geriatr Psychiatry. 2008;23(7):704–711.
http://www.ncbi.nlm.nih.gov/pubmed/18181229
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Low Dose Possibility:
Did come across one reference that suggested some neuroprotection can occur with serum levels of 0.2 mmol/l and up though.
Also, there is one new study using 0.3 mg (300 ug) lithium/day in Alzheimer’s that found no progression of decreased mini-mental status over 15 months versus deterioration in control group.
Andrade Nunes, Marielza, Tania Araujo Viel, and Hudson Sousa Buck.
“Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimers disease.”
Current Alzheimer Research 10, no. 1 (2013): 104 -107.
http://www.ingentaconnect.com/content/ben/car/2013/00000010/00000001/art00014
Final consensus is in a recent review:
Neuropsychiatr Dis Treat. 2013;9:493-500.
Lithium and neuroprotection: translational evidence and implications for the treatment of neuropsychiatric disorders.
Diniz BS, Machado-Vieira R, Forlenza OV.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627470/pdf/ndt-9-493.pdf
“Current evidence points to a potential role of lithium as a drug with disease modifying properties in AD.”
Nunes, Marielza Andrade, et al.
Chronic microdose lithium treatment prevented memory loss and neurohistopathological changes in a transgenic mouse model of Alzheimer’s disease.
PloS one 10.11 (2015): e0142267.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142267
Abstract
The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer’s disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd)20Lms/2J) and their non-transgenic litter mate genetic controls were treated with lithium carbonate (1.2 mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer’s disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained
Comment: – Whether that would take 0.3 mg/day or 300 mg+/day needs replication. You need to take a 300+ mg lithium carbonate/day or merely lick the open end of the capsule... I would combine this with enbrel shots interspersed as well. Actually, I have them dissolve a 300 mg capsule and take 1/10/day
addendum – had one patient on low dose lithium until her mid 80’s when she was taken off by an internist because her renal function as some compromised. She developed an outbreak of cold sores which is implicated in dementia, had teeth problems, and deteriorated significantly. Still wonder if she would have done better if she had stayed on low dose lithium. Studies keep coming out showing low dose lithium may slow down Alzheimer’s:
J Alzheimers Dis. 2020;73(2):723-739. doi: 10.3233/JAD-190862.
NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats.
Wilson EN et al
https://www.ncbi.nlm.nih.gov/pubmed/31868669