The debate about brain clearance and dementia
Brain fibre optics: how far can you go? Studying the link between poor sleep and early death in a neuroscientist’s study of dementia
Scientists have known about a link between poor sleep and an increased risk of dementia for decades. Maiken Nedergaard, a neuroscientist at the University of Rochester in New York, says that people who report six hours or less of sleep a night are more likely to develop dementia later. She said sleep problems were often preceded by the first sign of dementia.
Nedergaard believes she’s been able to create ways to get as close to real sleep as possible. “We spent years developing this fibre optic where we implant little fibres in the brain three weeks before we actually study the mice,” she explains. “These fibres are mounted in a hook, so the mice do not have to carry them on the head.” That detail is important, she says, because “if you have anything more than three or four grams on a mouse’s head, it cannot lift it and then, of course they can’t sleep. They get very upset.” In her latest paper3, she says, “we have mice that sleep completely normally”.
Sleep scientists have no shortage of questions to explore. These include the link between night-time illumination and mood disorders, the disappointing finding that napping might increase the risk of heart disease and the, perhaps self-evident, confirmation that early morning university classes discourage attendance and reduce learning.
Comment on “The great brain clearance and dementia debate” by F. Franks and J. B. Proulx, J. S. Nedergaard, P. C. L. Holtzman
Proulx and his team did not inject tracers directly into the brain, but instead into the fluid that surrounds it. “Most of the tracers that you inject into the cerebrospinal fluid don’t go into the brain. He says that most wash out towards the lymphatic system. “We went back to Nedergaard’s original 2013 paper and realized that she didn’t consider this other pathway for the tracers, which might mean that she has potentially misinterpreted some of her data.” Nedergaard does not accept the critique. Her work is valid, she says, because she’s interested in following the tracers that do enter the brain.
Nedergaard wrote to the editors of Nature Neuroscience to explain why she believes Franks’s paper shouldn’t have been published. She is worried that Franks might have injected too much material into the brain, causing brain wide impacts that alter neural activity. She also says that the paper fails to assess whether brain damage or inflammation were caused by the procedures, which could have skewed the results.
This back and forth might sound intense, but there is a lot at stake — most importantly, scientists’ foundational understanding of the pathology of dementia. And this knowledge ultimately guides the treatment of neurodegenerative diseases, says Holtzman.
Franks did not accept the criticism. He claims that the comment completely ignores the rate of injection. The damage here is unlikely according to the analysis, he asserts.
Source: The great brain clearance and dementia debate
What do we really know about the great brain clearance and dementia debate? Comment on Nedergaard, Franks, and the conversation in New York
Franks admits to being taken aback by the argument. “I felt like I was being invited to be ambushed and humiliated,” he says. “It wasn’t a meeting to really discuss whether we were right. It was political and it was about public relations.”
The disagreement has been very passionate. Franks was asked to a New York meeting in December of 2024 with other researchers to discuss his findings. Nedergaard says that Franks’s team was invited. Everyone told them that their paper is wrong.
Franks rejects this critique, and says that it’s perfectly legitimate to use innovative techniques in science and that if new ways of looking at a phenomenon disagree with the older methods, that’s scientifically interesting in its own right.
Franks says they have shown that the consensus about sleep clearing everything from the brain more quickly is not true.
His results show that tracing materials did not fall out during sleep. The concentration of the dye was greater during sleep and anaesthesia. This, says Franks, would suggest that sleep actually reduces clearance.
The January3 paper is one of many that support this explanation. In this latest paper, Nedergaard and her co-authors looked at whether zolpidem had an effect on brain clearance. Their data showed that the drug reduced glymphatic flow, potentially reducing the number of proteins that could be removed from the brain. That could explain why the drug affects memory negatively, and gives credence to the idea that increasing sleep by any means might not lower the risk of dementia — use zolpidem for long enough, Nedergaard says, and any gains from having had more sleep could well be wiped out by the negative effects. The risk is that you would accelerate the deposition.
Source: The great brain clearance and dementia debate
How Margaret Thatcher managed to run the country and what she did to protect herself against Alzheimer’s disease: a scientific critique of the work of experts and scientists
In response to this challenge, scientists have exchanged harsh criticism with some accusing each other of personal attacks and attempting to undermine the entire field of research. Tensions are running high.
The former UK prime minster Margaret Thatcher famously managed to run the country on just four hours of sleep per night. She embraced this as part of her personal brand and identity. In later life, the ‘Iron Lady’ was diagnosed with Alzheimer’s disease.
Birds are capable of doing it. The bees are responsible for it. Animals with no central nervous systems do it. Babies do it but it is less than their parents would like.
DoRA – a novel cancer drug for the treatment of insomnia: a review and opinion on cost and effectiveness of the dortaxes
There is progress in treating insomnia, which is the most common sleep disorder. The good news is that the past decade has seen the development of a class of drugs that effectively induces sleep without triggering anxiety and other side effects that have plagued previous insomnia therapies. The writer found that DORA drugs are difficult to get and expensive.
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Maiken Nedergaard, a neuroscientist at the University of Rochester in US, has claimed that people who report six hours or less of sleep a night are more likely to develop dementia later. In her latest paper, Nedergaard said that “we have mice that sleep completely normally”. She added that the fibers mounted in a hook can’t be carried on a mouse’s head.