With the advent of consumer genetic testing from 23andMe, AncestryDNA, etc, it is now easy to know if you are at a higher risk of getting Alzheimer’s Disease (AD). Those with APOE ε3 are at normal risk for Alzheimer’s, and those who carry an APOE ε4 allele (or two) are at an increased risk.
This is a touchy subject for some people, so please think it through before you check to see your APOE type.
One reason for learning your APOE type is to know if it is important to keep up with current research on preventing Alzheimer’s.
|APOE Allele||rs429358||rs7412||Risk of Alzheimer’s|
|ε2/ε4||C/T||C/T||slightly higher risk than normal|
|ε3/ε4||C/T||C/C||higher than normal risk|
Back to the topic at hand – preventing Alzheimer’s:
While tons of 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. I find this intriguing since 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.
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.”
Yep, this is just a mouse study and needs to be replicated in humans. But holy cow – 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 led 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 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.”
So what can you do with this information linking circadian rhythm dysfunction to AD? First, take a real look at your sleep quality and sleep environment. Second, it may be time to make some lifestyle changes to limit blue light at night.
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 candlelight 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.
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.
Before rocking the blue-blocking glasses in the evening, I would have told you that I slept well. And I did usually fall asleep easily… staying asleep all night was sometimes a problem, though. But I had no idea what good sleep was until I took the plunge and bout a cheap $10 pair of dorky looking blue blocking safety glasses.
I’ve gotten differing feedback from friends who I’ve talked into trying the blue-blocking glasses at night. A couple of friends had the same reaction that I had: incredible sleep, improved mood In the morning (almost giddy at first), and no plans to ever stop wearing the blue blockers. On the other hand, other friends and family have really struggled with giving the glasses a shot. They find that they need to take them on and off to put on reading glasses, or they need to take them off while taking out contacts. All in all, they aren’t seeing enough benefit to regularly wear the glasses, which may come from the intermittent light negating the effect.
Check out my Review of Blue-blocking Glasses.