While tons of Alzheimer's research money over the last couple decades has been spent on trying to find drugs to stop the tangled accumulation of beta-amyloid plaque without much success, a new direction of research is looking into the tie to circadian rhythm dysfunction. This is intriguing because the sudden increase in Alzheimer’s disease rate over the past few decades correlates with increasing chronic exposure to blue light at night, a circadian rhythm disruptor.

It has long been known that circadian disruption is a part of AD. Called ‘sundowning’, Alzheimer’s patients often are more active or confused in the evening /night and sleepy during the daytime. Often their normal sleep - wake cycle is thrown off, and this is particularly hard on their caregivers.

The chicken-or-egg question comes to mind:
Is Alzheimer’s caused by changing circadian rhythms  --or--  is the circadian dysfunction being caused by the disease.

A recent mouse study (Regulation of amyloid-β dynamics and pathology by the circadian clock) looked at this question. The study used a mouse type that is bred to accumulate amyloid-beta and also have a disruption of one of the core circadian genes, BMAL1. The results of the study indicate that disrupting the core circadian gene causes increased amyloid beta production and plaque deposits. From the conclusion: “Our results demonstrate that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid Aβ oscillations and accelerates amyloid plaque accumulation, whereas loss of peripheral Bmal1 in the brain parenchyma increases expression of Apoe and promotes fibrillar plaque deposition."  

Yes, this is a mouse study and needs to be replicated in humans. But the implications are huge– what if the increase in blue light at night, which directly acts to regulate BMAL1, is what is driving the increasing rate of Alzheimer’s disease?

So this lead me to dive into other studies on AD and circadian rhythm. There are a lot of studies and reviews looking at the connection between circadian rhythms and AD, but, as a 2017 review concluded, there is still a lot to learn about how and when circadian dysfunction interacts with the pathogenesis of AD.  

A 2015 article in the Journal Nature does an excellent job of summing up the research up to that time. The article brings up the research on disrupted sleep being an additive risk factor along with APOE e4. Experiments have shown that amyloid beta levels rise and fall in a daily circadian pattern, both in mice and humans. The study goes on to say (emphasis mine): “Sleep deprivation exacerbates Aβ plaque pathology while enhancing sleep by inhibiting orexin signaling attenuates plaque accumulation. Finally, sleep deprivation exerts a variety Aβ-independent effects in the brain that could exacerbate neurodegeneration. Because relatively small alterations in Aβ levels can translate into considerable changes in plaque pathology over a long timeframe,43 chronic mild sleep disturbances throughout life might conceivably facilitate Aβ deposition, setting in motion a feed-forward cycle in which Aβ pathology in turn impairs the sleep wake cycle.”

You can read the full (open) Nature article here: https://www.nature.com/articles/emm2014121

A study that came out in Feb. 2018 looked at how APOE ε4 genotype interacts with sleep cycles. It concluded: “Our findings suggest that the APOE ε4 allele may act as a moderator in the relationship between the sleep-wake cycle and Aβ accumulation in CN older adults. “

Another study that came out in January 2018 used a drosophila animal model of AD with tau accumulation. The study found that dim light at night caused disrupted circadian rhythms and neurodegeneration.  More research from 2017 using drosophila expressing human tau protein found: “we demonstrate that sleep can be used as a therapeutic to reverse deficits that accrue during the expression of toxic peptides associated with Alzheimer's disease.”  Again, these are animal studies which may or may not hold true for humans.

Lifehacks:

So what can you do with this information linking circadian rhythm dysfunction to Alzheimer's disease?
First, take a real look at your sleep quality and sleep environment.
Second, it is time to make some lifestyle changes to limit blue light at night.
Third, get more light during the day.

The study on dim light at night is a good reminder to make sure that you are sleeping comfortably in a really dark room. Put a piece of electrical tape over all the annoying little LED lights (or unplug them). If you need a clock in your bedroom, go with an automatically dimming red colored clock. And most importantly, put up some blackout curtains. It makes a huge difference in sleep to actually sleep in true darkness.

Why block the blue-light wavelengths before bed? Prior to the advent of electric lights, all we had for thousands of years was candle light or fire to light up the night. Then came the incandescent bulb, which has only a small amount of light coming from the shorter blue wavelengths. Finally, we all got color TV’s, LED or CFL light bulbs, and smartphones or tablets, all of which beam light in the short blue-wavelengths at us in the evenings.

Blue wavelengths decrease melatonin production.

What is the big deal about blue wavelengths? Our core circadian rhythm is reset each day with 480 nm wavelength (blue light). Humans used to get up each morning, go outside and reset their circadian rhythms with the 480 nm light coming from the sun.

Now, we are exposing our eyes well into the night to the specific wavelengths that indicate daytime. Circadian mismatch. We humans are resilient and can handle it for a time, but the chronic and pervasive bombardment of blue wavelength light at night is now linked to increased risk of cancer, heart disease, mood disorders, and diabetes.  

There is a great Popular Mechanics article that shows the wavelengths of different bulbs including CFL, LED and incandescent.

Screenshot from Popular Mechanic's article on wavelengths 

The other half of the light picture is that exposure to bright light during the day is also important.  This helps to shut of and suppress melatonin production during the day. The solution here can be as simple as maximizing the amount of time you spend outside.  Get up and have your cup of coffee outside each morning.  Eat lunch outdoors.  Walk to work – or park away from the office and walk for a ways in the morning sunshine.

Get outside during the day to be exposed to full spectrum daylight. 

For indoor lighting during the day, you want to maximize brightness in a full spectrum. Get some bright, full spectrum bulbs (label may say 'daylight', or 5000K) for your office or home to use during the day.  Then switch over to lamps with low-blue light bulbs for the evening hours (note that while I'm linking to Amazon so that you can see the light bulbs, they are also available, and currently cheaper, at Lowe's).