Why do people get too much sleep a night before they start to develop dementia? A neuroscientist’s perspective on the importance of a little extra sleep
Poor sleep and an increased risk of dementia have been known for a long time. 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. Sleep problems are often preceded by the first sign of dementia.
Nedergaard thinks that she has worked out ways to finesse the experiments 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.” She says that this is important because if there is more than a small amount on the head of a mouse, it will be hard for them to sleep. They are very upset. In her latest paper3, she says, “we have mice that sleep completely normally”.
There are plenty of questions to ponder by sleep scientists. The disappointing finding that napping could increase the risk of heart disease, as well as the link between night time illumination and mood disorders, are included in these.
The Claims of Proulx, Holtzman, and Nedergaard in the Great Brain Clearance and Dementia Debate
Proulx and his team’s experimental design was similar to Nedergaard’s — they did not inject tracers directly into the brain, but instead into the cerebrospinal fluid4. “Most of the tracers that you inject into the cerebrospinal fluid don’t go into the brain. They mostly wash out towards the lymphatic system,” he says. It was discovered that Nedergaard may have misinterpreted some of her data by going back to her original paper. Nedergaard rejects this critique. Her work is valid, she says, because she’s interested in following the tracers that do enter the brain.
Nedergaard, meanwhile, is keen to stress that the controversy transcends a disagreement between just her and Franks. “There’s a whole bunch of papers showing that sleep in humans facilitates brain clearance, so it’s not just our story or our hypothesis,” she says.
There is more at stake than this back and forth but scientists have a lot on the line. And this knowledge ultimately guides the treatment of neurodegenerative diseases, says Holtzman.
Franks rejects this criticism. “This comment completely ignores the critical parameter of the rate of injection,” he says. And factoring that into the analysis, he asserts, shows that “damage here is unlikely”.
Source: The great brain clearance and dementia debate
The Great Brain Clearance and Demensity Debate: Revisiting the Anaesthesia and Sleep Effects of Zolpidem
Despite anticipating such an argument, Franks admits to being taken aback. He says that he felt like he was being invited to be humiliated. “It wasn’t a meeting to really discuss whether we were right. It was political and it was about public relations.”
This has caused frustration to be met by Nedergaard. If you wish to disrupt an entire field, you need to use the same method. That’s a must if you’re disputing already established facts from many different groups. You can’t come in with completely different techniques,” she says. Someone who doesn’t know the field is behind it.
Franks says that using innovative techniques in science is always legitimate, and that if new methods don’t agree with the old ones, that’s scientifically interesting in its own right.
Scientists who back Nedergaard and her team say that it’s because the brain clears the proteins during sleep. Some people that support Franks say they don’t know. Franks believes that sleep is the best time to reduce the synthesis of genes.
The tracing materials did not fall out during sleep, according to his results. In fact, the concentration of the dye was higher during both anaesthesia and sleep. This, says Franks, would suggest that sleep actually reduces clearance.
She has co-authored a bunch of papers that support this explanation. The authors looked at the effects of zolpidem 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. There’s a risk that you accelerate the amyloid- deposition.
Source: The great brain clearance and dementia debate
The Iron Lady slept four hours per night: a reminder from Margaret Thatcher’s legacy to the science of brain clearance in the 21st century
Amid this challenge to the prevailing brain-clearance theory, scientists have exchanged harsh criticisms, with some accusing others of personal attacks and attempts to upend an entire field of research. The tension is high.
Margaret Thatcher, the former prime minister of the UK, only had four hours of sleep per night. She embraced this as part of her personal brand and identity. The Iron Lady was diagnosed with Alzheimer’s disease in later life.
Birds do it. The bees do it. Even animals without central nervous systems do it. Babies do it, albeit less than their parents would like.
Recent Developments in Treatment of Insomnia: The Case for DORA Drugs (Invited Editorial), Contributed by Avadel
There’s also progress in treating what is by far the most common sleep disorder: insomnia. The good news is that over the past decade a class of drugs has been created that are able to induce sleep without causing anxiety and other side effects that have been a problem with previous insomnia therapies. The DORA drugs are hard to obtain and expensive, as our writer discovered.
We are pleased to acknowledge the financial support of Avadel in producing this Outlook. As always, Nature retains sole responsibility for all editorial content.