Didn't your competent? doctor already figure out what to do with lithium after stroke and TBI? Oh no, NOTHING WAS DONE? And they are still employed there after proving incompetence?
Lithium May Combat Alzheimer's Disease, Data Suggest
Key Takeaways
- Endogenous lithium levels were lower in the prefrontal cortex of people with Alzheimer's and mild cognitive impairment.
- Lithium depletion in mouse models led to increased amyloid and accelerated memory decline.
- Disrupted lithium homeostasis may be an early Alzheimer's trigger, suggesting new therapeutic possibilities.
Endogenous lithium may have a physiological role that affects brain aging and vulnerability to Alzheimer's disease, postmortem human samples and mouse experiments suggested.
Of 27 abundant and trace metals in the blood and brains in older adults with either normal cognition or cognitive decline, only lithium showed significantly reduced levels in the prefrontal cortex of people with amnestic mild cognitive impairment and Alzheimer's disease, according to Bruce Yankner, MD, PhD, of Harvard Medical School in Boston, and co-authors.
In a second independent cohort, lithium levels were significantly reduced in the prefrontal cortex of people with Alzheimer's, Yankner and colleagues reported in Natureopens in a new tab or window.
Although zinc was increased and copper was decreased in people with Alzheimer's disease, lithium was the only metal with significantly reduced levels in both mild cognitive impairment and Alzheimer's brains. This was true for both men and women.
In mice, lithium depletion accelerated brain pathology and memory decline, Yankner and colleagues showed. Feeding wild-type and Alzheimer's mouse models a lithium-deficient diet reduced endogenous cortical lithium and led to higher amyloid-beta levels, phosphorylated tau accumulation, synaptic loss, and accelerated cognitive decline.
Amyloid appeared to draw in lithium from surrounding tissue and sequester it. Replacement therapy experiments showed that amyloid plaques trapped standard lithium carbonate, but a novel lithium orotate compound avoided capture and restored memory in mice.
The findings indicate a physiological role for endogenous lithium and suggest that a disruption of lithium homeostasis may be an early event in Alzheimer's pathogenesis, Yankner and co-authors concluded.
"The idea that lithium deficiency could be a cause of Alzheimer's disease is new and suggests a different therapeutic approach," Yankner said in a statement.
The findings were consistent with previous research suggesting that naturally occurring lithium in drinking wateropens in a new tab or window may have contributed to a decline in dementia incidence in Denmark, the researchers noted.
Lithium is naturally present at low, micromolar concentrations in the blood and brain, observed Ashley Bush, MBBS, PhD, of the University of Melbourne in Australia, in an accompanying commentaryopens in a new tab or window. "Its pharmacological effects have historically been considered a quirk for a metal ion with no obvious physiological purpose."
However, this study presents "compelling evidence that lithium does in fact have a physiological role, and that normal aging might impair the regulation of lithium levels in the brain," Bush wrote.
"The work opens up a world of possible functions for lithium at micromolar concentrations -- for example, [lithium] could be a signaling ion similar to copper (Cu+), which was reported a few years ago to have a signaling role at trace concentrations," he added.
The findings also introduce the idea that formulation plays a role in determining lithium's therapeutic target. Lithium carbonate has been the mainstay of bipolar treatment for decades, Bush noted. "Orotate and other formulations have been considered and await evaluation for neuropsychiatric disorders," he said.
"Apart from the implications for treating Alzheimer's disease, the data invite a re-evaluation of lithium-salt variants as treatments for older adults with bipolar disorder," Bush added.
"An abnormal build-up of amyloid is common with age, and it precedes dementia by more than 15 years," he pointed out. "Lithium sequestration by amyloid could explain why it is difficult to achieve mood-stabilizing effects in older people with bipolar disorder, and it suggests that older people with bipolar disorder might be better treated with orotate than carbonate."
If replicated in further studies, lithium screening through routine blood tests may offer a way to identify people at risk for Alzheimer's disease who might benefit from treatment, the researchers suggested.
Lithium has not been shown to be safe or effective in protecting against neurodegeneration in humans, Yankner emphasized. The findings need to be validated in clinical trials and by other labs.
"My hope is that lithium will do something more fundamental than anti-amyloid or anti-tau therapies, not just lessening but reversing cognitive decline and improving patients' lives," he said.
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