A day on Alzheimer's disease

On Friday I attended a series of seminars on Alzheimer's disease at the University of British Columbia's Brain Research Centre. I think the idea was to showcase Canadian research in the field of dementia to woo politicians (also in attendance) and ask them for more funding. We heard about all aspects of Alzheimer's disease, from its history to its treatment, and in this post I will fill you in on the latest developments.

Alzheimer's disease is the number one public health problem in the developed world, with approximately 35 million cases worldwide. In Canada it represents a very expensive problem, estimated to cost 50 million dollars a day. In the time it takes you to read this post, there will be two more people diagnosed with Alzheimer's in Canada. As there are currently no approved treatments that affect the disease itself, there is an urgent need to keep our heads down and power through (bonus points for whoever can identify this reference in the comments) to find a cure.

The first "official" patient with Alzheimer's disease was a 51-year old woman named Auguste Deter. She was examined by Alois Alzheimer in 1901. She suffered from impaired memory, aphasia (a language disorder) and disorientation. Alzheimer kept meticulous records: we have a very detailed description of Auguste's condition, and even a sample of her handwriting (see picture). Even though the condition was described in great detail, Alois Alzheimer did not know what had caused Auguste's disease. Today, as one of the researchers at the seminar pointed out, we still don't know what causes Alzheimer's disease, but on a much higher level.

We do know that one of the main culprits in Alzheimer's disease is amyloid beta (Abeta), a protein that everybody's brain makes. In the brain of an Alzheimer's patient, though, too much of this protein is being made, and it aggregates in toxic chunks called plaques. The researchers present at the seminar predicted that vaccines against these plaques will fail. However, there are several candidate drugs that could prevent or treat these plaques in clinical trials right now.

Interestingly, researchers are also studying naturally occurring compounds: one of the speakers talked about his research looking at whether natural extracts can block the formation of plaques in a "petri dish" model of Alzheimer's (brain cells grown in a dish). He finds that ginger, cinnamon, turmeric, cranberry, rhubarb, blueberry, pomegranate and blackberry all help prevent the aggregation of Abeta. However, he warns that at this point, it is not practical to focus on eating these foods because the concentrations used in the lab are just not possible to recreate in a diet.

Beyond the molecular and biological underpinnings of Alzheimer's disease, researchers are also addressing the inevitable changes the world will need to undergo to accommodate a growing prevalence of dementia. For example, one speaker pointed out that many public places such as airports and even hospitals are very difficult to navigate for cognitively healthy people: this represents a true disservice to people with Alzheimer's disease. Efforts are also being made to engage the public (as to avoid more bad news like this one), and to provide resources for caregivers (such as the fantastic First Link initiative).

Overall, I'm disappointed to report that I didn't learn of any magical intervention that will rid us of Alzheimer's disease, but it's comforting to know that there is a big research community out there who is taking this problem very seriously and who is tackling it from many different angles.

You are what you eat

The race to develop a drug to treat Alzheimer’s disease is a top priority for many pharmaceutical companies. With the aging population, the size of the market is ever increasing, and some people estimate that the winner of the race will pocket several billion dollars in the first year of a drug being on the market, in the US alone. However, it would be far easier if we could simply find a way to decrease our risk of getting Alzheimer’s disease in the first place. One recent study suggests that it’s as easy as eating healthy.

We’ve known for a long time that what you put in your plate is the single most important modifiable environmental factor for your risk of getting a variety of diseases, ranging from obvious ones like scurvy (drink your OJ!) to less obvious ones like prostate cancer (stay away from red meat!). Given these relationships, a team of researchers decided to study what combination of foods may relate to a risk of getting Alzheimer’s disease. They asked over 2000 elderly subjects to describe their eating habits in great detail, then followed them for 4 years.

After the 4 years had passed, 253 subjects had developed Alzheimer’s disease. After careful analysis of the subjects’ diets, the researchers concluded that the following diet characteristics significantly lowered your risk of developing Alzheimer’s disease:

• The diet is rich in omega 3 and 6 fatty acids
• The diet is rich in vitamin E and folate
• The diet is poor in saturated fatty acids
• The diet is poor in vitamin B12
• Eating salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables is correlated to a decrease in the risk of Alzheimer’s disease
• Eating high-fat dairy, red meat, organ meat, and butter is correlated with an increase in the risk of Alzheimer’s disease.

Subjects who adhered best to the characteristics described above saw their risk of developing Alzheimer’s disease drop by 38%. By now, I’m sure my alert Scientific Chick readers are already wondering if the researchers looked at other factors, such as age. Differences in age, education, ethnicity and sex didn’t change the relationship between diet and Alzheimer’s disease. However, other factors did lessen the importance of the diet, such as smoking, body mass index, and caloric intake. But even when controlling for all these factors, the relationship between diet and risk of developing Alzheimer’s disease remained significant.

The major strength of this study is that it looked at existing dietary patterns instead of trying to impose them, which is often unreliable. However, some of the results can be misleading. A low intake of vitamin B12 may seem to protect you against Alzheimer’s disease, but it’s because a lot of food that contains B12 (such as meat and dairy) also contain high levels of saturated fats, which increase your risk for Alzheimer’s disease. Overall, as with any scientific study, the results must be interpreted carefully. It’s a combination of foods that is important: you can drink antioxidant-rich blueberry juice all you want, but if you’re having it with a side of ground beef, you’re missing the point. In addition, there could be some factor other than diet at play that the authors did not control for.

So while we don’t have a miracle drug yet, and no single food can prevent Alzheimer’s disease, it seems like a healthy, varied and unprocessed diet is a good place to start to ensure healthy aging.

P.S. It's Jello.

Reference: Food combination and Alzheimer disease risk: A protective diet (2010) Gu Y et al. Arch Neurol [Epub ahead of print]

Cell phones: curing brain diseases since 2010

If you are like most people, and in particular like everyone I take transit with on a daily basis, you probably spend a fair amount of time talking on your cell phone. If that’s the case, you’ll probably be happy to learn that in 2007, the World Health Organization declared that cell phones are A-ok. Nothing to worry about health wise. Not at all like sticking your head in a microwave. But you’ll be even happier to learn that in 2010 (fresh off the press!), a study published in the Journal of Alzheimer’s Disease suggests that not only is using your cell phone harmless, it might actually be good for you.

The researchers looked at the effect of exposing mice to high frequency electromagnetic fields (similar to the ones you are exposed to when chatting on your cell phone) for a long period of time (2 hours a day for 8 months). They used both normal mice and a mouse model of Alzheimer’s disease. An Alzheimer’s mouse is a transgenic mouse that has a gene that causes some of the manifestations of Alzheimer’s disease in humans.

At the start of the study, before the exposure to the electromagnetic fields, the researchers tested the mice on memory tasks, and as expected, the Alzheimer’s mice were clearly impaired compared with the normal mice. After two months of exposure, no change was observed in either type of mouse. However, after 8 months of exposure to the cell phone-like electromagnetic fields, the Alzheimer’s mice did significantly better on memory tests compared with Alzheimer’s mice who didn’t receive the treatment. Normal, non-Alzheimer’s mice also showed cognitive benefits due to the electromagnetic fields compared with normal mice that didn’t get the treatment.

Time to get Grandma a cell phone? Not so fast.

You may have seen this story in the news. It may have sounded like we finally found a cure for Alzheimer’s disease, and, as a bonus, it’s non-invasive and has no side effects. You may have started thinking of a business plan that involves sewing cell phones into pillowcases for the elderly. Trust me, I thought of this. However, as per usual in the world of science, it’s probably not that simple.

First, I can tell you this: mice skulls are thin, weak, and very easy to cut through with just a regular pair of tiny scissors (how sad is it that I know this from experience?). The skull of a mouse is very different from that of a human, and this means that while the electromagnetic field might penetrate well into mice brains, this may not happen in humans.

Second, the mouse model of Alzheimer’s disease, while widely used and our best tool for these types of studies, is flawed. So extrapolating the results to human Alzheimer’s disease is definitely premature.

Third, if you read the article carefully (I did it for you, so no worries), you’ll find that exposing the older mice to electromagnetic fields has one interesting side effect: an increase in body temperature. It then becomes difficult to tell if the memory enhancement observed is due to the temperature change or the electromagnetic fields. However, this is not necessarily a bad thing. I, for one, would much prefer to prevent cognitive decline by a daily regimen of quiet hot baths then by talking on the phone (though when I was a teenager, my mom would have guessed otherwise).

Finally, there was another sneaky side effect to the exposure, one that was seen only in younger mice: a decrease in three brain compounds involved in battling oxidative stress, including a very important antioxidant. The authors go over this finding somewhat quickly, and suggest that this can be interpreted as a good thing. Unfortunately, I happen to have studied this particular antioxidant quite a bit and I am of the opinion that the finding can also be interpreted as a very bad thing.

Overall, I don’t want to sound like a complete downer. This study was well conducted, showcases very interesting findings, and certainly gives us hope that maybe something can be done for Alzheimer’s disease. But I won’t be sowing a cell phone in my pillow just yet.


Reference: Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer’s disease mice. (2010) Arendash GW, Sanchez-Ramos J, Mori T, Mamcarz M, Lin Z, Runfeldt M, Wang L, Zhang G, Sava V, Tan J, Cao C. Journal of Alzheimer’s Disease 19:191-210.

Yet another reason for a good night's sleep

How much do you sleep at night?

If you’re like most of the people I know, the answer is “not enough”. There’s a reason Starbucks coffee shops are popping up literally meters away from one another. Everybody has a reason to be sleep-deprived: new kid, big job, World of Warcraft, etc. So what if we’re cutting the night short a few hours? Other than the need for an overpriced coffee (or two, or three), it should be just fine, right?

Maybe not, if you believe the latest research on sleep and Alzheimer’s disease.

Alzheimer’s disease, a debilitating form of memory loss and cognitive decline, is the most common form of dementia. It is thought to be caused at least in part by amyloid beta (A-beta), a peptide (short protein). Your brain cells (neurons) normally make some A-beta. The problem that arises with Alzheimer’s disease is that neurons make too much A-beta, and these molecules aggregate together in chunks. It’s those A-beta chunks that are toxic, and their formation is concentration-dependent, which means the more A-beta you have floating around, the higher the probability of toxic chunks forming.

The recent article published in the journal Science looks at levels of A-beta in the brains of normal mice and in the brains of a mouse model of Alzheimer’s disease. The researchers studied the mice when they were 3 months of age, so well before big deposits and chunks of A-beta start occurring.

The interesting finding of this study is that the levels of A-beta in the brains of both types of mice were significantly correlated with the amount of time they spent awake. More time spent awake lead to more A-beta. Because the control, normal mice also exhibited this relationship, it means that it is not linked to the disease. It’s just a normal fluctuation of A-beta levels linked to the sleep-wake cycle. To be certain this link was relevant for human physiology, they also tested this in healthy humans and, sure enough, they observed the same correlation.

Not surprisingly, when the researchers proceeded to sleep-deprive the mice, they showed an even larger increase in A-beta levels. This increase was also observed when the mice were given a drug that promotes wakefulness (don’t extrapolate this to coffee just yet… But maybe keep it in mind…). The study also points out that the Alzheimer mice who are sleep-deprived showed much greater numbers of A-beta chunks (the toxic stuff) compared with non sleep-deprived mice.

If you come to Scientific Chick for relevant findings, this one is for you. The study essentially implies that optimizing sleep time could potentially inhibit the formation of chunks of toxic A-beta and slow the progression of Alzheimer’s disease.

We all know that Alzheimer’s disease is terrible, and that sleeping in is glorious. Let’s just put two and two together, shall we? Easier said than done, I know…

Mr. Minou gave up on caloric restriction but approves of this new approach to ward off age-related diseases.

Reference : Amyloid-{beta} dynamics are regulated by orexin and the sleep-wake cycle. (2009) Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM. Science Sep 24. [Epub ahead of print]

Yet another reason to exercise

Last weekend I went for a bike ride and when I reached the bottom of the big hill leading to UBC, I noticed quite a bit of activity going on. I didn't pay too much attention at first, but once I was booting up the hill, I was passed by several senior citizens on top-notch bicycles and I started getting curious. I asked a person who seemed to volunteer for the event what was going on. As it turns out, I was cycling right in the middle of the BC Seniors Games. Now for those of you who might not know me, my thesis research has to do with aging and the brain and nothing warms my heart like witnessing older adults and seniors exercising. I had just hit the jackpot!

The reason I'm so enthralled to see seniors exercise is because it is the single best thing they can do to preserve their brains. Today's paper highlights recent research done in California that shows just that.

First, a bit of background. You have a gene called APOE (mice also have it). It comes in 3 flavors, and each person only has one of the three: APOE2 (not important for today’s article), APOE3 and APOE4. If you got lucky and scored the APOE3 kind, all is well. If you happen to be in the 20-25% of the population who has the APOE4 kind, you may be in trouble: APOE4 is a known risk factor for Alzheimer's disease. Does it mean you'll for sure get Alzheimer’s disease? No, but you are 10 to 30 times more at risk of developing Alzheimer's disease if you carry the APOE4 gene.

In this paper, researchers compared old APOE3 (normal) and APOE4 (at risk for dementia) mice. In general, aged APOE4 mice experience cognitive decline faster and earlier than APOE3 mice. The researchers were interested in studying whether exercise (running on a mouse wheel!) had any effect on this cognitive decline.

The researchers used cognitive tasks that rely on a part of the brain that's important for memory, the hippocampus. One of the tasks, called place recognition, involves putting a mouse in an arena with two objects. The mouse is then removed from the arena, one object is moved, and the mouse is put back in the arena. Presumably, a normal mouse will then spend more time exploring the object in the new location. For this task, the aged APOE4 mice were initially impaired compared with the APOE3 mice. This means that during the second trial of the task, they tended to explore both objects for similar amounts of time, instead of spending more time on the object at the new location. This result suggests that the APOE4 were unable to remember the initial object locations well. The good news? Mice who exercised did significantly better at this task. Interestingly, this was valid for both APOE3 and APOE4 mice. Even more interestingly, exercise improved the scores of both types of mice for all the tasks that tested the hippocampus.

What's going on in the brains of these exercising mice? It is thought that exercise increases the levels of a protein called BDNF (for Brain-Derived Neurotrophic Factor). BDNF regulates many important functions in the brain, including the making of new neurons and the making of new connections between neurons, and these effects are thought to be important for memory.

Regular readers of Scientific Chick know not to get too excited when I report about animal studies. Well, I'm happy to add that the results that were observed in those mice were also observed in humans. In fact, there are countless human studies out there that confirm that physical activity is a powerful way to improve and maintain your cognitive abilities.

When I try to urge certain people to exercise (you know who you are), I almost always hear the same excuse: “Well, my uncle so-and-so never got off his couch and he lived to be 100!” In some cases, heredity can be on your side, that's true. But genetics can be quite the lottery, and it's important to keep in mind that several forms of cognitive decline, including the most common form of Alzheimer's (called “sporadic” in scientific lingo) are not hereditary.

So to all my older readers out there, I'll see you on the road at next year's BC Seniors Games. And if you're not ready for cycling, there's always the cribbage category.

Winners from this year's BC Seniors Games, cycling event. This could be you!

Reference: Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice. (2009) Nichol K, Deeny SP, Seif J, Camaclang K, Cotman CW. Alzheimers Dement. 5(4):287-94.