Breakthrough study finds deficiency of this common nutrient could contribute to Alzheimer's
The decade-long research, published in the journal Nature, shows for the first time that lithium occurs naturally in the brain and maintains the normal function of all its major cell types, preventing nerves from degradation.
Scientists from Harvard Medical School found that lithium loss in the human brain is one of the earliest changes leading to Alzheimer's, while in mice, a similar lithium depletion accelerated memory decline.
A reduced lithium level was found in some cases due to the metal's impaired uptake and its binding to amyloid plaques, which are known to be smoking gun signs of Alzheimer's.
Researchers also showed that a new type of lithium compound – lithium orotate – can avoid capture by amyloid plaques and restore memory in mice.
In the study, scientists used an advanced type of mass spectroscopy chemical analysis method to measure trace levels of about 30 different metals in the brain and blood samples from a range of people, including cognitively healthy people, those in an early stage of dementia, and those with advanced Alzheimer's.
The analysis revealed that lithium was the only metal with markedly different levels across groups, which also seemed to change at the earliest stages of memory loss.
'Lithium turns out to be like other nutrients we get from the environment, such as iron and vitamin C,' study senior author Bruce Yankner said.
'It's the first time anyone's shown that lithium exists at a natural level that's biologically meaningful without giving it as a drug,' Dr Yankner said.
Although lithium compounds have been historically in use to treat a range of mental conditions like bipolar disorder and major depressive disorder, in these cases, they are given at much higher concentrations that could even be toxic to older people.
Scientists have now found that lithium orotate is effective at one-thousandth this dose – enough to mimic the natural level of lithium in the brain.
The latest findings with lithium orotate, however, needs to be confirmed in humans via clinical trials.
Yet, researchers suspect that measuring lithium levels could help screen people for early Alzheimer's.
The findings revise the theory of Alzheimer's disease, which affects nearly 400 million people worldwide, offering a new strategy for early diagnosis, prevention, and treatment.
Decades of studies have shown that Alzheimer's disease involves an array of brain abnormalities, including clumps of the protein amyloid beta, tangles of the protein tau, and a loss of the brain's protective protein REST.
However, these abnormalities have never fully explained the condition.
For instance, it remains unclear why some people with Alzheimer's-like changes in the brain never go on to develop dementia or cognitive decline.
Recent treatments developed to target amyloid beta plaques also don't seem to reverse memory loss, only modestly reducing the rate of cognitive decline.
Now, scientists say lithium could be the critical missing link.
'The idea that lithium deficiency could be a cause of Alzheimer's disease is new and suggests a different therapeutic approach,' Dr Yankner said.
'You have to be careful about extrapolating from mouse models, and you never know until you try it in a controlled human clinical trial... But so far the results are very encouraging,' he added.
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On supporting science journalism If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. To gain a snapshot of how the wider community interprets quantum physics in its centenary year, Nature carried out the largest ever survey on the subject. We e-mailed more than 15,000 researchers whose recent papers involved quantum mechanics, and also invited attendees of the centenary meeting, held on the German island of Heligoland, to take the survey. The responses — numbering more than 1,100, mainly from physicists — showed how widely researchers vary in their understanding of the most fundamental features of quantum experiments. 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The German physicist Werner Heisenberg, who helped to craft the mathematics behind quantum mechanics in 1925, and his mentor, Danish physicist Niels Bohr, got around the alien wave–particle duality largely by accepting that classical ways of understanding the world were limited, and that people could only know what observation told them. For Bohr, it was OK that an object varied between acting like a particle and like a wave, because these were concepts borrowed from classical physics that could be revealed only one at a time, by experiment. The experimenter lived in the world of classical physics and was separate from the quantum system they were measuring. Heisenberg and Bohr not only took the view that it was impossible to talk about an object's location until it had been observed by experiment, but also argued that an unobserved particle's properties really were fundamentally unfixed until measurement — rather than being defined, but not known to experimenters. 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The similar 'relational quantum mechanics', first outlined by Rovelli in 1996 (and selected by 4% of respondents), says that quantum states always describe only relationships between systems, not the systems themselves. When asked specific follow-up questions about how to view aspects of quantum mechanics, researchers' opinions differed sharply, as could be expected from the variety in overall interpretations they favoured. One question that elicited a mix of answers relates to one of the weirdest aspects of quantum mechanics: that the outcomes of observations on entangled particles are correlated, even if the particles are moved thousands of kilometres apart. This potential for distant connection is referred to as non-locality. The connection doesn't allow faster-than-light communication. But whether it nevertheless represents a kind of real and instantaneous influence across space-time, such that measuring one particle instantly changes its entangled partner and affects the results of future measurements, is something that respondents disagreed on. In the survey, 39% of respondents said they thought that such 'action at a distance' was real. The remainder either weren't sure or disagreed in a variety of ways. If respondents answering 'yes' meant to imply that a physical influence is travelling faster than light, this would conflict with Einstein's special theory of relativity, says Flaminia Giacomini, a theoretical physicist at the ETH. 'This should worry every serious physicist,' adds Renner. 'I'm puzzled.' However, some respondents, such as those who take epistemic views, might have answered 'yes' but have interpreted instantaneous influence to mean merely an instant change in their information, rather than a physical effect, says Giacomini. Nature also asked about the 'double slit' experiment — in which electrons are sent towards a screen with two slits. On the other side of the screen, a detector shows a pattern that tallies with wave-like particles going through both slits and interfering with themselves. (If researchers observe an electron en route, such as by putting a detector on either slit, the pattern changes to suggest that the particle passed through only one.) Asked whether an unobserved electron travels through both slits, 31% agreed, an answer that fits with the many-worlds interpretation but, the survey suggests, is also the view of reality taken by many followers of the spontaneous collapse and Copenhagen approaches. However, 14% said it didn't, which fits with the Bohmian-mechanics view of definite electron trajectories, and 48% said the question was meaningless — a response given by the majority of epistemic and Copenhagen adherents. 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In 2024, when Hartmut Neven, founder of Google Quantum AI in Santa Barbara, California, announced the firm's Willow quantum chip, he argued that its ability to perform a calculation that would take longer than the age of the Universe on the fastest classical computer 'lends credence to the notion that quantum computation occurs in many parallel universes'. He was referring to a 1997 extension to the many-worlds theory by David Deutsch, a physicist at the University of Oxford, UK. Agreeing on a single interpretation might be a case of coming up with a new approach altogether. 'Once we find the correct interpretation, it will announce itself by virtue of offering more coherence than anything before,' says Spekkens. 'I think we should aim for that.' Whether the current state of affairs is a problem or not depends on who you ask. 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Compared with the least fit individuals (METs, 4.8), the CRC risk was 14% lower in those falling in the low-fit CRF category (METs, 7.3), 27% lower for moderately fit people (METs, 8.6), 41% lower for fit individuals (METs, 10.5), and 57% lower for high-fit individuals (METs, 13.6). Moderate CRF is attainable by most middle-aged and older individuals, by engaging in moderate-intensity physical activity such as brisk walking, which aligns with current national guidelines, the authors said. The study was published online on July 28 in Mayo Clinic Proceedings. The results dovetail with earlier work. For example, in the Cooper Center Longitudinal Study, men with high mid-life CRF had a 44% lower risk for CRC and a 32% lower risk of dying from cancer later in life men with low CRF. A recent meta-analysis for the World Cancer Research Fund estimated a 16% lower risk for colon cancer in people with the highest levels of recreational physical activity relative to those with the lowest levels. 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'There is good evidence that exercise and healthy lifestyle/diet have significant benefit overall and as well for some potential risk reduction for colon cancer,' David Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Virginia, told Medscape Medical News. 'There are clearly suggestions of why this makes sense via the beneficial effects of exercise and physical activity in CRC pathways including but not limited to regulation of inflammation and aberrant cell growth/cancer pathways,' Johnson said. He emphasized, however, that exercise and lifestyle are not the best way to prevent CRC. 'Appropriate screening, in particular by colonoscopy (by skilled physicians who meet high-quality performance national benchmarks) to detect and remove precancerous polyps, is the best approach for prevention,' Johnson said. 'At this point — albeit exercise is potentially helpful and a great general recommendation — my most current advice as an expert in the field, is that you cannot outrun CRC risk,' Johnson said. Can You Outrun CRC Recurrence? Prevention aside, the data thus far are even more supportive of risk reduction for patients who have had CRC and are targeting reduction of recurrence, Johnson said. Perhaps the most compelling study was recently published in The New England Journal of Medicine. The CHALLENGE trial enrolled patients with resected stage II or III colon cancer who had completed their adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. Participants were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. The focus of the exercise intervention was increasing recreational aerobic activity over baseline by at least 10 METs — essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging three to four times a week. At a median follow-up of nearly 8 years, exercise reduced the relative risk for disease recurrence, new primary cancer, or death by 28% ( P = .02). 'This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively,' Johnson noted in a Medscape commentary. The CHALLENGE results are 'very compelling,' Bishal Gyawali, MD, PhD, associate professor of oncology at Queen's University, Kingston, Ontario, Canada, noted in a separate Medscape commentary. 'If you compare these results with results from other trials, you'll see that this is a no-brainer. If this were a drug, you would want to use it today,' Gyawali said. Saltzman told Medscape Medical News patients often ask him what they can do to help prevent their cancer from coming back. 'I would sort of say, 'Well, eat a healthy diet and exercise,' but I didn't have a lot of good evidence to support it.' The CHALLENGE study provides 'the proof in the pudding.' With these strong data, 'it almost feels like I should be able to write a prescription for my patient to join an exercise program and that their insurance should cover it,' Saltzman said.
