Lack of Sleep May Lead to Dementia: New Research Finds It Makes Brain Vulnerable

By Eli Wolfe

It turns out that a sleepless night may cost you more than a morning of grogginess—it could be giving the proteins believed to cause dementia easier access to your brain.

Scientists at UC Berkeley’s Sleep and Neuroimaging Lab have discovered evidence that missing out on deep non-REM (rapid eye movement) sleep may leave the brain more vulnerable to the memory loss associated with Alzheimer’s disease.

Alzheimer’s disease, one of the most pervasive and debilitating forms of dementia, has been diagnosed in more than 40 million adults. As the massive Baby Boomer generation continues to gray over the next decade, this number will likely spike.

The study, published in Nature Neuroscience, found that beta-amyloid—a protein that has long been suspected of being a catalyst in Alzheimer’s—aggregates in higher concentrations in the brains of people who suffer from consistently poor sleep. As deposits of beta-amyloid grow, the protein further hampers one’s ability to sleep, which feeds into a miserable cycle that may lead to dementia.

UC Berkeley neuroscience professor Bryce Mander co-led the study with Alzheimer’s expert William Jagust, a professor at Berkeley with a joint appointment at Lawrence Berkeley National Lab. They and their colleagues were intrigued by recent animal research that suggested a reciprocal relationship between lack of sleep and the beta-amyloid pathology. Their cross-sectional study was designed to test whether the relationship between poor sleep and beta-amyloid aggregation had any actual bearing on memory loss.

“What was unknown was whether or not that’s just a side relationship that has nothing to do with the clinical symptoms of dementia, or if sleep disruption is part of why these toxic chemicals in the brain are causing memory loss,” Mander explains.

The researchers selected a group of 26 adults aged 65 to 81 who were not currently suffering from any form of dementia or sleep disorders. First, each subject underwent a positron emission tomography (PET) scan to measure the concentration of beta-amyloid in their brains. Within a year, they came back to the lab and memorized 120 word pairs. They then slept for eight hours while their brain waves were measured with EEGs. The next day, they were scanned with functional magnetic resonance imaging (fMRI) to measure their brain activity while they tried to recall the word pairs.

The results from the scans revealed that individuals with the highest concentration of beta-amyloid in their brains experienced the worst sleep during the study and performed poorly on the word pair test. According to Mander, this indicated that beta-amyloid has a direct impact on memory by ruining the sleep required for building memories.

“This is not to say that amyloid and other pathologies can’t impact memory independent of sleep,” Mander says. “But it does suggest that part of the way it impacts memory is through sleep-dependent memory.”

Anyone who has ever racked up a nasty sleep deficit knows that it ruins your capacity to recall information. But there’s a good reason for this. During deep sleep—also known as slow wave sleep, when the brain is experiencing non-rapid eye movement—memory “traces” become reactivated, which triggers communication between the hippocampus and the cortex. The communication between these regions of the brain helps maintain the neuroplasticity that is required to “cement” long-term memories in the cortex, which can be retrieved hours or years later.

Past attempts to treat or reduce the build-up of beta-amyloid in the brain have failed to restore any meaningful cognitive abilities to people suffering from dementia. According to one theory, this protein eventually triggers a cascade of other events that lead to neuro-degeneration, so getting rid of the protein won’t simply “cure” the brain of other problems.

“You may reduce amyloids in those treatments, but you don’t treat the symptoms, and in some cases it continues to worsen,” Mander says. “It’s like cleaning the rubble after an earthquake hit—that doesn’t keep the earthquake from doing its damage.”

Mander believes that with this new understanding of beta-amyloid, researchers could start to harness it as a biomarker to assess which individuals are at a greater risk of developing Alzheimer’s. The good news is that beta-amyloid starts to build up in healthy adults well before the onset of symptoms of Alzheimer’s. So if it could be detected early through screening, it might be possible to delay the onset of more severe symptoms of dementia.

Researchers elsewhere were cautiously optimistic about the results. “This study builds on previous work suggesting that sleep is important for both consolidating new memories and for clearing potentially toxic proteins from the brain,” Douglas Galasko, a professor in the Department of Neurosciences at UC San Diego, who was not involved in the study, wrote in an email. “An intriguing possibility is that interventions to improve sleep may benefit pathways of amyloid formation. This deserves further study.”

Meanwhile, any practical advice for people who want to make sure they are achieving quality deep sleep? Although there may be some pharmacological remedy in the future, Mander cautions that trying to induce those Slow Waves in the brain with a sleeping pill would be tricky—and getting it wrong could possibly exacerbate memory problems. Experts advise that the easiest way is probably to exercise regularly. There is also an experimental technique known as transcranial direct-current stimulation, which exposes a person to a low-level current set at a frequency that matches the slow waves associated with deep sleep. And some potentially useful techniques rely on even stranger science.

“There’s even this one wacky method where you have people wear headphones and you play pink noise,” Mander says. “It’s not white noise, and it’s not this incidental event that will wake you up and startle you—it’s this specific pattern of acoustic sounds that are in time with the oscillations of your slow waves.”

Mander’s team recently received a grant from the National Institute on Aging so they can conduct a longitudinal study to see if the results from their first study stay true over time. Part of this study will be devoted to the cart/horse question: decisively figuring out whether beta-amyloid triggers sleep loss, or sleep loss causes beta-amyloid build up.

“That can give us a better sense of the causal chain of events,” Mander said. “And that will then be used to help inform us when we think about any future intervention studies where we try to enhance sleep.”

Share this article:
Google+ Reddit


HI all, FOA, congrats for a so interesting article. I have always been a deep sleeper throughout my whole life. I am 51 now and continue to be a deep sleeper whenever possible. (in fact if nobody awakes me I can sleep like 12 or 14 hours and sometimes I think this might bring some issues too?). I am curious to know about something related to deep sleeping and dreams: 1- I tend to believe that I don’t sleep well during some nights but then I remember I was dreaming. Is it possible that existence of “dreams” can prove that we have slept deeply or considerable well? Or we must trust on the bad-sleeping feeling we experience in the morning (and therefore having dreams) is not relevant towards raising any kind of conclusion that proves deep sleeping or the opposite? 2- Sleeping too match can be a symptom of any disorder related to the investigation? I am sorry if you think these are wired questions and thanks again for the quite interesting note. Alejandro Rivas UC Berkeley graduate from UNEX 2003 class.
Good to know.
CAA and sleep. Are they connected.
I have chronic microvascular Ischemic decease and I was just told I have the beginning of dementia, are those two related. Sincerely Lis Christensen I am 80 years old.
In a similar way that the bio-accumulation of toxins in the body (stored in fats, etc.) has cumulative effects over the long-term, so too it seems, does the lack of sleep (or sleep debt) been found to impair Aβ clearance from the brain. The seeming connection between dementia (generically) and AD cannot be dismissed any longer. We humans used to live by the seasons and the sun, not the clock. Once we monetized time itself, and created artificial light and urbanized, we fell away from living naturally by the natural pulse of Earth. Trying to overcompensate this with pharmacology will be disastrous.
Hello, great article on the relationship between sleep and dementia. When I was a freshman in high school, my grandmother got Alzheimer’s and so I have been personally affected by this illness and I try to find whatever information exists to figure out how I can prevent this in myself and others. I try to get access to whatever current research papers I can get my hands on and study them to learn as much as possible, and I plan to become a researcher in this field, after hopefully finishing medical school. I could relate to the findings of this investigation. Indeed, lack of sleep does seem to have a relationship with the ability to recall information. We all know sleepless nights studying don’t work. I have had my fair share of those, and in my experience, lack of sleep will lead to getting a worse grade than if you get a good night’s sleep. Side note: I had a teacher in high school who would emphasize the day before our final exam: Do not stay up and study, you will do better if you don’t stay up and study. Anyway, this study was interesting in that it appeared objective and scientific. I would be interested in hearing more.
My wife was diagnosed with Alzheimers one year ago but has shown symptoms for last six years. She holds a Phd in psychiatric nursing and published research in the area of childrens’ mental health. During a good part of her research years she was sleep deprived due to her devotion to her work. She was very driven. A neurologist at Mayo clinic was extremely interested in a possible relationship between her growing memory loss and her sleep deprivation. I don’t believe there was any research in this area then. I do know that he remarked that if he had suspected a relationship between dementia and sleep deprivation when he was in med school he would have gotten more sleep. His statement has haunted me ever since . I would be very interested if my wife, Jan, would qualify for any upcoming clinical trials. This is the first time I have seen any meaningful research in this area. Thanks for any help you might be able to give.
Thanks for this wonderful post. The writer has taken a lot of time and effort to post this information on the website. As a matter of fact, no points of arguments are left for the audience as the information is sound and authentic. The anecdotes are combined carefully with ingenuity and what comes out in the end is really interesting. By:
I wonder when sleep medicine practitioners will learn about these issues. I’ve been trying to get help from sleep medicine for chronic sleep deprivation since age 30, but they are only CPAP doctors who have no interest or skills in finding the causes of nonrefreshing and limited sleep. I’ve consistently used the CPAP treatment since I was diagnosed with mild sleep apnea but it my sleep problems have only worsened. The masks are made of cheap, uncomfortable plastic and are only available in 3 standard sizes for the entire population and variety of faces. Sleep studies don’t include use of the patient’s machine, so no one evaluates the function of the machine used nighty. Sleep software/freeware is available to analyze the data from my machine, and I’ve beought the data to 5 different doctors but they are not interested in the data. Their only solutions-did you try another mask? I can order a new sleep study, etc. I imagine the people who have really severe apnea are helped by this treatment, but most of us are somewhere in between. The sleep apnea forums are full of people begging for help as doctors do not problem solve. Sleep medicine is a joke. I see all this interest in the research, but no one seems to care about helping people in practice. The disconnect between research and clinical care remains wide. I am young but have memory problems from only getting 4 or 5 hours of unfreshing sleep for years, and my body is breaking down. Despite all the technology in the world that already exists in practice that can be used to problem solve at least some of the causes of the sleep problems, I am slowly dying but cannot find any help from medicine. A close relative got dimentia in his late 40s and did at 55 from the same. With the magnitude of dementia, you would think medicine would try to problem solve but they only order CPAP machines and hand out a paper on sleep hygiene or antidepressants. I’ve tried to tell them the nerve from my left side of my neck that goes to my diaphragm muscle feels irritated, and it feels like there is structural blockage to my lymph flow of vessels in my neck and head on the left side, and they either say something sarcastic or treat me like a hypochondriac. Why can’t they at least look at the data from the machines? Why can’t they at least look at blood flow of lymph blockages or nerve compressions when someone isn’t helped by treatment after years of consistent but unsuccessful treatment? I’ve been thinking for years that blocked lymph flow to the head or circulation mechanisms to the brain can’t clear out the proteins, toxins, etc. but there is no one who will look into the possibility of a structural blockage or impingement despite being such a simple concept (ie, look at vessels and flow of fluids in lymph system and circulation to neck and brain. See if a vessel or nerve is compressed.) Why can’t researchers help us. Can somebody please help us? I’d rather die a quick death than further live through this torturous sleep deprivation. Please help us.
Diagnosed with moderate to severe sleep apnea about ten years ago, my sleep since then has been very erratic. Now aged 83, I get between 3 to 5 hours sleep a night. My brain seems to cut off at 5 hours. I wake up, read, return to bed, follow all the rules for good sleep hygene, including Matthew Walker’s instructions in Why We Sleep. Forgetfulness has been present for a number of years and in the last three months it has progressed to the point where I feel my brain will not function at all in the near future. It is now difficult to learn anything. Twice my sleep neurologist prescribed medications which were addictive, the last one was Lunestra, which I did not take. CBT has not worked either. Please, can any one help me? Brenda Diaz
Mother died from dementia. I have been diagnosed with severe sleep apnea (loud snoring and stop breathing). My memory of details/specifics has changed. Not complete forgetfulness of a topic often just specifics i.e. names. The previous discussion was very helpful.
I wanted to share my recent journey with high blood pressure medication, sleep and dementia in hopes that it will help others. I am 59 years old. Both my parents had dementia and died at ages 78 & 79. I have high blood pressure and take amlodopine and auro-olmesartan. Just as Covid 19 was arriving in Quebec, my husband and I moved 2 hours away to be closer to our children and grandchildren. in the Montreal area. I had had high blood pressure for years and was taking amlodopine and auro-olmesartan. Due to a lack of supply caused by Covid, auro-olmesartan was not available and the new pharmacy recommended I take telemisartan. I took telemisartan for 5 months. During that time, I started experiencing memory loss—my daughter lived a 3 minute drive from our new home in a neighbourhood with lots of twisting streets and I could not drive to her house without using the GPS. One day, I was driving my 3 year-old grand-daughter home and she told me, “Oh, Grandma, you turned the wrong way!” Out of the mouths of babes! Since my husband and I were both retired, I was able to easily orchestrate us going out on errands together so that I would not have to drive. Five months after I started taking the telemisartan my daughter told me she was worried about me and had noticed I was experiencing memory loss. I went to the doctor and she put me back on my original blood pressure medication. I was relieved to be off the telemisartan and thought my memory issues were behind me. But by July, I was still having bigger memory issues—I couldn’t remember what I had for breakfast, lunch or dinner. I started leaving myself notes on the bathroom mirror. In preparation for a doctor’s appointment I had scheduled for mid-July, I started researching amlodopine and learned that one of the side effects was having trouble sleeping. Since menopause, I’d had trouble getting to sleep. I thought it was just part of growing older. I remember my mother often got up in the middle of the night and read when she couldn’t sleep. Thankfully, I called my doctor and booked an appointment. It turns out that I’m sleep deprived. For years! My doctor told me to go to the drug store and buy some melotonin. (non-prescription). And to take one pill about 30 minutes before bedtime. The first night I definitely felt more sleepy than I had in a long time. After 5 days of sleeping about 8 hours a night, I was seeing huge improvements in my short-term memory. I could actually remember what I had eaten for breakfast, lunch and dinner the previous day. And, on waking in the morning, I no longer feel like my brain is a void.