Alzheimer's Disease Possibly Linked To Sleep Deprivation

sonnejw0 writes "NewScientist is reporting a link between sleep deprivation and Alzheimer's Disease via an increased amyloid-beta plaque load thought responsible for a large part of the symptoms of the disease, in mice. Medication to abrogate insomnia reduced the plaque load. Also discussed is a recently discovered sleep cycle of amyloid-beta deposition in the brain, in which levels decrease while asleep. 'Holtzman also tried sending the mice to sleep with a drug that is being trialled for insomnia, called Almorexant. This reduced the amount of plaque-forming protein. He suggests that sleeping for longer could limit the formation of plaques, and perhaps block it altogether.'"

Comments

Why do we sleep?

[bcmm]

Could delaying the inevitable onset of Alzheimer's be the biological function of sleep? Last I heard, the purpose of sleep wasn't entirely clear, and there were anecdotal reports of people basically eliminating it with drugs, sometimes with little ill-effect. I've long been of the opinion that if wakefullness promoting agents don't have short-term effects, there must be a longer-term negative impact, because if there weren't, the body would synthesise something similar, at least in people who are sufficiently well-fed not to mind the extra energy usage. Sleeping is basically a good chance to get eaten.

It's going to be a long time before we find out if regular modafinil users get early Alzheimer's.

P.S. It's been over an hour, and it still isn't possible to reply to this article. I'll post this when Slashdot works. I predict about 30 people claiming First Post.

Re:Why do we sleep?

[rastilin]

Could delaying the inevitable onset of Alzheimer's be the biological function of sleep? Last I heard, the purpose of sleep wasn't entirely clear, and there were anecdotal reports of people basically eliminating it with drugs, sometimes with little ill-effect. I've long been of the opinion that if wakefullness promoting agents don't have short-term effects, there must be a longer-term negative impact, because if there weren't, the body would synthesise something similar, at least in people who are sufficiently well-fed not to mind the extra energy usage. Sleeping is basically a good chance to get eaten. It's going to be a long time before we find out if regular modafinil users get early Alzheimer's.

I'd credit your theory; however there has been some research that shows Caffeine can also act against Alzheimer's. When consumed regularly it appears to slow it's progress as well as somewhat mitigating the symptoms.

Re:Why do we sleep?

[DrLang21]

There is no such thing as sleep deprivation without short term ill-effects. We know that cognitive ability declines with a lack of sleep, even if it's a small lack of sleep ever night over an extended period of time. Your cognitive ability and reaction time will continue to decline until you start getting complete sleep. In fact, after a few weeks, people with sleep deprivation begin to perceive that they're "getting used to it" and are going back to normal in spite of their continued decline.

Re:Why do we sleep?

[smprather]

I have zero proof, but I've always figured sleeping was simply a low power state to go into since we're highly optimized to operate in well lit conditions. Then the body then found some other useful things it could do while sleeping, like imprinting recently learned patterns in the brain.

Re:Why do we sleep?

[Jurily]

Sleeping is basically a good chance to get eaten.

I suspect sleeping has a higher level function as well, like getting rid of all the crap you accumulate in your head throughout the day. Maybe some (perhaps non-essential, just useful) chemicals in our brain tend to run out when awake, and sleep is needed to restock them.

However, awake is only one state of mind out of many, it'd be foolish to disregard most of them. (I don't consider "auto-pilot on the highway" awake, for example.)

Re:Why do we sleep?

[Jah-Wren Ryel]

Sleeping is basically a good chance to get eaten.

Not necessarily. Wandering around in the open is probably a lot more dangerous than being holed up in a lair - especially if your sensory organs are optimized for night and it is day or vice versa. Plus, animals and people are very highly attuned to certain noises while asleep - basically if it sounds like something is approaching or entering the lair most animals will quickly transition from sleep to fully awake.

Re:Why do we sleep?

[bcmm]

Of course, the term "wakefulness promoting agent" is used to distinguish drugs like modafinil from traditional stimulants like caffeine. Going without sleep with caffeine usually means you have to catch up, and, in my own experience, doesn't stop you getting stupider after several hours. Modafinil supposedly allows one to stay up all night, functioning normally, and only require the normal amount of sleep the night after they come off it.

Re:Why do we sleep?

[bill_mcgonigle]

Could delaying the inevitable onset of Alzheimer's be the biological function of sleep? Last I heard, the purpose of sleep wasn't entirely clear

What? No. There are at least two functions of sleep that I know of: one is cleaning up misshapen proteins that accumulate during the day (and may be what causes tiredness). The other is transcription of short-term memory into long-term memory. Evolutionarily speaking, nobody ever lived long enough to get Alzheimers. Those who did wandered off into the tundra and didn't burden the tribe any longer.

Re:Why do we sleep?

[Kohath]

You first point is (seemingly) correct. Sleep is not evolution's way of preventing Alzheimer's Disease. Your second point is incorrect.

Healthy old folks are directly beneficial to social groups. They remember how to solve problems. They can take care of grandchildren while the parents are off gathering food. And many social groups had old folks. Sure, most people didn't live to get very old. But some did.

Re:Why do we sleep?

[bill_mcgonigle]

Healthy old folks are directly beneficial to social groups. They remember how to solve problems. They can take care of grandchildren while the parents are off gathering food. And many social groups had old folks. Sure, most people didn't live to get very old. But some did.

That's absolutely true of grandparents, but we're talking about great-great grandparents here, from a bio-evolutionary standpoint.

Re:Why do we sleep?

[fuzzyfuzzyfungus]

Hmm. Sounds like we need alarm clocks that sound more like approaching leopards...

Re:Why do we sleep?

[fuzzyfuzzyfungus]

The presence of large numbers of old people makes hunting for food way easier. If you aren't picky.

Re:Why do we sleep?

[demonlapin]

Well, the Schedule II rating is a very easy way to quit getting prescribed. Amphetamines work, and they're cheap. But you *can* get high with them, so we have to restrict the crap out of them. [Insert drug war rant.]

OTOH, they're not without downsides. See, amphetamines work by increasing the catecholamine (particularly norepinephrine) levels in the brain. They push the catecholamines out of the storage vesicles into the synapses. (FWIW, cocaine works by preventing neurotransmitters from being absorbed back into the neuron that released them - it doesn't change the amount released.) So, after a few days straight of amphetamine use, you crash HARD - you no longer have any catecholamines, so you can't stay awake. A pharmacist friend of mine told me of a story told by some of her professors who had trained in the 50s, when amphetamines were either OTC or just plain prescription (not scheduled). Guys would keel over in the middle of final exams because they had been awake for 3 straight days, finally ran out of norepi, and couldn't stay awake. No solution for it but to let them have 12-24 hours to synthesize more.

Also linked to lyme disease...

[Gicuenitro]

Alan MacDonald, M.D., is a pathologist affiliated with St. Catherine of Siena Medical Center in Smithtown, New York. His current research is concentrated on developing what he refers to as a new biology for Lyme disease, including the use of special DNA probes to detect Borrelia DNA in spinal fluid and in tissue sections from Alzheimer autopsy tissues.

Through his research, and with the help of other leading researchers in the field of molecular and cellular biology, Dr. MacDonald is pioneering a broader understanding about the behavior of Borrelia burgdorferi, the bacteria that causes Lyme disease. He has appeared as an invited lecturer at Lyme symposia, including the ILADS National Scientific Meetings and Columbia University/Lyme Disease Association conferences in Philadelphia, PA, where he presents the findings from his explorations into the connection between Borrelia spirochetal infection and Alzheimer's disease.

Dr. Alan MacDonald: "Using the syphilis model, I began to study some autopsied brains, and found that I was able to identify spirochetes in autopsied brain tissue in the hippocampus, which is one of the areas that Alzheimer's disease tends to target in every patient. I was able to grow spirochetes from autopsied Alzheimer's brain tissue, and stain the spirochetes with special monochromal antibodies, through the techniques I learned and developed through the study of stillborn babies with Lyme disease. And those two positive results made me think even more strongly that some Alzheimer's might be like syphilis, a late manifestation of the bacterial infection in the brain, not to say that all Alzheimer's disease is related to Lyme disease, but some."

Not enough is known about Lyme Disease and its relation to Alzheimer's, ALS, MS, Fybromyalgia, etc. But, you can be sure Dr. MacDonald will be at the forefront.

Got an idea if you don't have time for sleep

[vehicle tracking]

Why don't we all just start taking Holtzman?

I stayed up all night...

[nycguy]

...trying to think of a clever comment, but now I forgot it!

Implications for other Mental Diseases?

[FormerUpper]

Could this plaque, and its base cause of sleep deprivation also be the cause of some mental illnesses? I have heard that Alzheimer's Disease resembles both Schizophrenia and Bipolar. Maybe this might have implications for those tragic diseases.

Re:Implications for other Mental Diseases?

[demonlapin]

No. Antipsychotics are generally dopamine receptor blockers. While this does produce sedation (and weight gain), they are not sleeping pills. Interestingly enough, the first antipsychotics to be discovered were found by projects that were trying to find antihistamines, which were sedative because they were (accidentally) also anticholinergics;

Re:Implications for other Mental Diseases?

[Ethanol-fueled]

I don't know much technical details, but I know of this one because I've taken it. From the article:

Seroquel...an atypical antipsychotic...sometimes used off-label...to treat such conditions as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression...and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.

Take a look at that. Sleep is a key point, if not the key point of many of the disorders listed above. Even alcoholism, because alcohol prevents good sleep. You take the drug so that you pass out before you reach for the bottle. The good sleep alleviates symptoms which cause one to reach for the bottle in the first place. So on and so forth.

Taking the drug is exactly like slipping into the relief of a hypnagogic state.

Re:Implications for other Mental Diseases?

[demonlapin]

I'm a practicing physician with a strong interest in pharmacology. I do know the technical details. Unfortunately, I apparently suck at making a point, because this is the second comment in this thread that I've had fall victim to my unclear phrasing.

To amplify: They are sedative, but they are most assuredly not glorified sleeping pills - a benzodiazepine, a barbiturate, or a central anticholinergic would be what people think of as sleeping pills, and none of those would work.

They act as "mood stabilizers", a property discovered early on (Thorazine, for example, was advertised as useful for calming the "agitated senile" patient.) This, not their sedative effect, is why they're useful for psychosis and psychiatric illness. The sedation is unfortunate but unavoidable - many, many schizophrenics won't take antipsychotics because they can't stand the feeling of being so mentally slowed.

Do Naps Count?

[tunapez]

I went 2-3 days w/out sleep in college, now(15 years later) I can hardly make it through the day without a nap.
7 hours a night is my minimum or I am definitely off my A Game that day. Some nights I need 10.

  What happened to needing less sleep as we get older?

Re:Do Naps Count?

[Jim Hall]

I had the same thing as you - in college, I could go more than a day without sleep. I'd definitely be dragging that second day, but I could do it. After college, and as time wore on, I found that I just needed more and more sleep. On weekends, I would sometimes get 12+ hours of sleep - and I'd still be tired!! I'd sometimes take naps on weekend afternoons.

For me, the problem was that I had obstructive sleep apnea. That's where you stop breathing when you fall asleep (your brain wakes you up just enough that you start breathing again, but not enough that you become aware that you woke up.) Most people who have sleep apnea aren't even aware they have a problem, they just assume you should be tired all the time.

I was finally diagnosed last year, and I did a sleep study**. They gave me a CPAP machine - I wear the mask whenever I sleep, and the CPAP machine pushes air into me. Effectively, it's inflating my airway so it doesn't close during the night. I'm a totally different person now! I don't need naps, and I sleep about 7-8 hours a night before I wake up normally.

If you're feeling the same way (naps during the day, needing more time every night to get rested) you might want to see a sleep specialist and ask for a sleep study.

My [twin] brother reported similar symptoms as you, and I eventually convinced him to see his doctor about it. Turns out, he also has apnea, got a CPAP, and is much better.

** For you fellow CPAP users out there, let's compare numbers: I had 57 sleep disruptions per hour, and my CPAP pressure is 14, no EPR.

Re:Do Naps Count?

[phantomfive]

The three pillars to good health: sleep, nutrition, and exercise. If one of them is missing, the rest all goes downhill.

With the old people I've talked to who need less sleep, it seems they are also at the same time not quite getting the exercise and proper nutrition they need to keep their body sustained. Sleeping is work for your body, it spends the time in repairs. If you don't have the right nutrients, it's harder.

Sometime try fasting for a couple days and see how it affects your sleep. Instead of skipping food completely, you can try going on a 900 calorie diet for a while. Pretty soon you will find that your don't sleep as long, but that you aren't as well rested either. The worst is when you sleep a full six hours, but find you feel as though you haven't slept at all.

If you don't eat all the nutrients you need, say you don't eat enough vegetables, the same thing will happen to you, but on a longer scale. It may take years for the lack of broccoli in your diet to show up in your body, but eventually it will, and you will feel it. That happens to a lot of old people.

As a graduate student...

[magsol]

...I am SO screwed. I think.

Re:As a graduate student...

[Burnhard]

Me too. I've had around 2 weeks of decent sleep in the last two years and those two weeks were gained by taking sleeping pills after I crawled into the Doctor's surgery barely alive!

Re:As a graduate student...

[fuzzyfuzzyfungus]

Don't laugh, college boy...

Amyloid-beta Desposits != Dementia

[DynaSoar]

Alzheimer's suffers have amyloid-beta plaque deposits in their brains. Usually. Not always.

There are people who have amyloid-beta deposits in the brains. Some of them have dementia, including Alzheimer's. Not all.

Amyloid-beta plaque can be cleared from the brain by immunization. The dementia occurs anyway.:
AB42 Immunisation Clears Brain Plaques, Does Not Prevent Dementia ...
http://www.pslgroup.com/dg/225f1e.htm

Thus, this article should read "Amyloid-Beta Plaque Desposition and Clearing Possibly Associated With Sleep", and any implied link to Alzheimer's saved until the discussion section at the end.

Re:Amyloid-beta Desposits != Dementia

[DynaSoar]

Alzheimer's suffers have amyloid-beta plaque deposits in their brains. Usually. Not always.

There are people who have amyloid-beta deposits in the brains. Some of them have dementia, including Alzheimer's. Not all.

Amyloid-beta plaque can be cleared from the brain by immunization. The dementia occurs anyway.:
AB42 Immunisation Clears Brain Plaques, Does Not Prevent Dementia ...
http://www.pslgroup.com/dg/225f1e.htm

Thus, this article should read "Amyloid-Beta Plaque Desposition and Clearing Possibly Associated With Sleep", and any implied link to Alzheimer's saved until the discussion section at the end.

There is a family of amyloids associated with Alzheimer's and dementia, of which AÃY42 is only one. While AÃY42 is typically the quickest to aggregate, AÃY40 can cause dementia just as easily (though it takes a lifetime to aggregate enough of it).

"... can cause dementia just as easily ..." implies a persistent belief in causation despite the reference providing evidence that one of the two obviously is not causative. What can be taken as adequately supported understanding of causation is the fact that Ab40 accumulation (by far the majority of plaque deposit) is seeded by the earlier accumulation of Ab42 (and 43) that forms tendrils much faster, attracting Ab40 out of 'diffuse plaque', the solution of non-tendrilled amyloid beta proteins with a hydrophobic C-terminal sequence anywhere from the 39 to 42 locus.

It likely takes much more than a lifetime to accumulate the kind of plaque deposition seen in AD from Ab 40 in the absence of tendril forming Ab42 accumulations. And, as stated by the reference above, and implied by the wording of most publications on the subject, there is plenty of evidence associating both Ab40 and 42 to AD, but not supporting causation.

Ref for my reply: http://neuro.psychiatryonline.org/cgi/content/full/11/1/19

Thanks for challenging me, I enjoyed it.

But... But... But...

[Greyfox]

A while back they said that caffeine could prevent or slow the disease. Since then I've been drinking 12 cups of coffee a day and sleep on average 30 minutes a night! And now this? Bastards!

Re:But... But... But...

[sonnejw0]

Caffiene helps by dilating blood vessels, supplying the brain with more oxygen, glucose, and most importantly the removal of toxic reactive oxygen species. At least that's what I thought.

Re:How does this apply to ...

[Rainbird98]

Well, it doesn't. Reagan was noted as a not a hard working president, early to bed, late to rise type guy. Yet, he died of this disease. Of course some people think he was a rat, so maybe the analogy applies.