• Question: People are less likely to develop Alzheimer's if they are happy, and 60 percent less likely to develop the disease if they drink coffee. Coffee gives a caffeine high. The effects on the hippocampus are similiar to that of depression. Is it possible that Alzheimer's is a form of depression or vice versa?

    Asked by Scarlett to Amy, Helen, Nicolas, Daniel, Thorrun on 17 Jun 2017.
    • Photo: Helen Frost

      Helen Frost answered on 17 Jun 2017:

      Hi Scarlett,
      I remember we briefly talked about this in our live chat, but it’s a fantastic question, so I’m glad we can go into some more detail. You’ve got a really great investigative mind, because you’ve cleverly linked different ideas together, to create a theory – that’s exactly how science works. However, in this case, you need a few extra details about all of these different issues to help unpick the logic.

      So, let’s start with the caffeine. A ‘caffeine high’ is not the same as happiness (or the opposite of depression). It’s a biochemical response to the chemical, which causes your heart rate to increase, your blood pressure to go up, your pupils to dilate, etc. It’s true that caffeine stimulates the cells in your brain to start firing more quickly, so it’s definitely affecting your brain, but not in a happy/sad way. Some people feel that as an exhilarating feeling, a bit like a tiny, mini version of being on a rollercoaster.

      OK, so now let’s turn to Alzheimer’s itself. You rightly linked effects on the hippocampus and depression, but that’s only a part of the story, because the hippocampus is only a part of the brain, and mood fluctuations are only part of Alzheimer’s. Imagine a complicated machine, like a car engine. There’s a small rotating part inside a car engine called a spark distributor, which spins around when you turn on the ignition, to send a tiny spark of electricity to spark plugs, which in turn, get the engine going. That’s how you turn on a car with the tiniest movement of turning a key (or pushing a button). If you remove or damage the spark distributor, the engine cannot start. You’d get in to the car, turn the key and absolutely nothing would happen. But equally, if you removed the battery, then you’d get the same outcome when you sat in the driver’s seat and turned on the ignition: absolutely nothing would happen. So now you have to look under the bonnet to see: is the battery gone, or is there something wrong with the spark distributor? Or is it something else, entirely? So, one outcome from a complicated machine can be caused by different, but connected/related things.

      Going back to the hippocampus, if you meddle with it, you will alter it’s ability to process and store memories, emotions and knowledge. So those emotional disturbances can seem very similar to the symptoms you see in patients suffering from depression, but they’re only a part of the picture. Memory loss and confusion are not what you think of in depression, but they’re classic symptoms in Alzheimer’s.

      We still don’t exactly know what causes Alzheimer’s, but what we know for sure is that it’s incredibly complex. Probably lifestyle and genetics play a role, but random bad luck could also be a factor. Careful studies have shown that people who suffer prolonged spells of depression throughout their lives can start to lose cells in the hippocampus, so it shrinks over time. Perhaps this is an early triggering factor for Alzheimer’s in some cases, but they’re not the same disease. It’s like saying that flattening the battery of a car damages the spark distributor – it doesn’t, but the two are connected because of their shared role in starting the engine.

      This has been a very long and rambling answer, but I hope you can see that the truth is we don’t know all there is to know about the brain and it’s troubles.

    • Photo: Thorrun Govind

      Thorrun Govind answered on 18 Jun 2017:

      People with Alzheimer’s disease can suffer from significant depression but this can partly be due to them having a long term condition. People with a long term condition are more likely to suffer depression.

Comments

  • Photo: Scarlett

    Scarlett commented on :

    Thank you again 🙂 @helen that was quite eye-opening and informative. It’s quite amazing how extensive the brain is, when it hardly takes up much space. I really hope the cause and cure is discovered soon (my grandma had alzheimer’s, but she wasn’t ever really unhappy) Does the caffeine help fight against plaques and tangles with the chemical reaction it causes to take place?

  • Photo: Helen

    Helen commented on :

    Hi Scarlett,
    I’m really sorry to hear that your Grandma developed Alzheimer’s. It’s a horrible disease, and I also really hope the cause/cure can be found soon. You should know that there’s a huge number of laboratories and companies out there devoting resources to solving this exact problem, so it will happen eventually. Your question about caffeine and the plaques is another excellent one, and to be honest I don’t know much about the effects of caffeine on protein turnover when plaques (or ‘aggregates’) form. I can tell you that caffeine has been shown to increase the natural turnover of ‘normal’ proteins, so for example in sport science it’s known that athletes who consume a small amount of caffeine after an intense training session (where proteins in their muscles get damaged) recover more quickly than if they don’t consume caffeine.

    Let’s talk about the plaques in the brain which are the hallmark of Alzheimer’s. There are other diseases which are caused when proteins that aren’t folded properly, or that have accidentally ended up in the wrong part of the cell, start to clump together and form these tangled, sticky aggregations. Parkinson’s disease is an example, also ALS (amyloid lateral schlerosis – remember the ice bucket challenge??). All of our cells are producing proteins, and sometimes those proteins get folded into the wrong shape, or get directed to the wrong place, but we have clever mechanisms in our cells to detect these ‘wrong’ proteins and recycle them. Cells have tiny machines called ‘chaperones’ which attach to a faulty protein and either re-fold them properly or guide them to the part of the cell where they will be broken down back into the amino acids they were built from. So, when this detection and repair mechanism breaks down, that’s when faulty proteins don’t get dealt with, and so they accumulate, causing more and more toxicity to the cell. Usually cells will realise that they are starting to experience this toxicity and they will launch something called a ‘stress response’ and start producing more of those chaperones to clear away the aggregates, but in these diseases, for some reason the cells don’t seem to realise they’re under any stress, possibly because the diseases develop over such a long period of time. In my company, we’re working on a treatment for this kind of accumulation of aggregated proteins. The treatment works by stimulating the cells to produce more of those chaperone proteins, or in other words, by stimulating a stress response in cells which have been under-reacting to stress. We have seen lots of positive results in cells and in animal models for a couple of different protein aggregation diseases, but the next stage in developing any medicine is to do a carefully controlled clinical trial in patients, and this takes a long time, and costs huge amounts of money. That’s where we’re at right now, trying to test this medicine in clinical trials. Then, if the results look positive, we will have to apply to the authorities to get permission to market the drug. At that stage, even if we think the results are conclusive, the regulatory authority could still reject the application and not allow us to make the drug available. It’s an extremely long, complicated and expensive process, but we’re working on it, and so are many others with drugs which work in different ways, so there’s lots to be hopeful for!