Brains at the Brink: Bruce Willis & FTD
Exploring FTD and its links to Parkinsons and Prion diseases
Recently, it was revealed that actor Bruce Willis has developed a form of Frontotemporal Dementia, a particularly early-forming dementia that often strikes between the ages of 40 and 60. Bruce is 68. When news came out initially about it, I was quite shocked that someone so young could develop dementia without some obvious cause of traumatic brain injury. I had never previously heard of FTD, but I knew the broad outline and mechanics of some Alzheimers family of diseases.
I can only imagine the pain that Bruce's family must be experiencing having to watch a loved one deteriorate like that. More than an actor who played some of the most defining action heroes in cinema history, he's also a father and a husband. Bruce Willis made such an enormous contribution to culture across the world, and I know that he had many more years to give. I wish there was more that could be done.
So, having not previously known about this specific condition, I went deep into a rabbit hole on FTD. This is more or less a break down of some of the things I think I discovered down there. None of this will be relevant to Bruce's specific condition, only his doctors and specialists can know that. In the spirit of my previous post on Parkinsons disease, and due to all the lovely messages I had from people, I thought it might be time for another deep dive into things that go wrong sometimes in the brain. Lets make this into a series.
Note: I am not a doctor, nor medical professional. Nothing I write should ever be seen as medical advice of any sort. Always see a real doctor or medical professional. This article is purely my personal thoughts, wild speculations, and uneducated babble. Anything which may sound vaguely medical is purely coincidental.
Jumping in
Looking specifically at behavioural-variant FTD, many strange things happen to the individual, from a behavioural perspective. A loss of inhibition can occur, leading one to follow their compulsions without control, such as binge eating. They might stop washing, start irrepressibly touching things that they wouldn't or shouldn't, that don't belong to them, like other people’s food. They might even start trying to eat things that are not food. They might start shoplifting and stealing things. They gradually lose executive function, might develop tremor, stiffness, strange gaits and postures, repetitive speech, eventually even losing the ability to speak or communicate entirely.
Looks a lot like dementia, doesn't it? The one thing that I didn't notice in all of my digging was fear. It does not appear - from what I was able to read - that fear manifests in any particularly significant way, as one might expect to find in other Dementias. Fear is often the most confronting symptom of late-stage dementia. It's the one that moves our humanity the most when we see it, or hear it. Hospitals - places I've been many times as a patient - often have the sounds of this fear reverberating down their halls and echoing through their waiting rooms. No matter how many times you hear the screaming and moaning, it never fails to break the heart. If there's any silver lining to a condition like FTD, it might be that at least they aren't in sheer terror. In fact, one might say they get progressively less and less awareness, less and less concerned, with what is going on around them. That's probably the best we can hope for in the circumstances.
The pathology of FTD
Lets get a refresher on something with some interesting similarities and overlaps: Parkinsons. In the Genetic form of Parkinsons, the main problem - we think - is a clumping together of a specific protein - alpha-synuclein - creating "Lewy bodies" (i.e the "chunks" of these proteins), and this happens primarily in the neurons of the brain that secrete dopamine, in the Substantia Nigra Pars Compacta, which is where almost all other dopaminergic neurons in the brain obtain their dopamine from. Alpha Synuclein is essential for releasing neurotransmitters from the vessicles in which they are typically stored. When these clump up and become unusable, the dopamine becomes trapped in the vessicles, and at some point the neuron itself is physically destroyed, either from the Lewy bodies, or from trying to store too much neurotransmitter and bursting, or both, or neither. Without dopamine, essential functions of the brain that control things like movement, motivation, and decision making, cannot function.
There are a fair number of conditions of the brain that involve similar clumping together of proteins, causing all kinds of havoc. Parkinsons, some Alzheimers disease variants, Prion diseases, and so on, all exhibit some form of malfunctioning of proteins in the brain.
FTD is specifically a kind of "Tauopathy", where a specific protein structure, called a "tau", forms into tangles. Normally, Tau is structured like microtubules. When they start to tangle, they lose this essential structure, and deform into a protein mash. Tauopathies and Synucleopathies - the latter including most Parkinsonisms - are commonly overlapping. Some kinds of Parkinsons are also Tauopathies. ALS - a disease which afflicted several giant personalities, such as the late Stephen Hawking, and baseball player Lou Gehrig - is another similar illness, with a bit more in common with Prion diseases, however approximately 15% of sufferers go on to develop FTD as well. In fact, some 12% of Behavioural-variant FTD ("Pick's disease") can go on to develop an ALS-like motorneuron disease.
So, what about Prions?
Prions are utterly fascinating. So get this: a protein can one day be produced in a very particularly misfolded shape. It is done in such a way that somehow it can touch a normal protein of the same type and cause that normal protein to adapt the same shape as the misfolded one, which can then cause others to misfold, and on and on. This is called "templating". Proteins are not supposed to be pathogenic, but wouldn't you know it, they can do exactly that in very peculiar circumstances. They are also unstoppable. Once begun, there is no ending it.
"Mad-cow" disease is a prion disease, for example. Its proper name is Spongiform Encephalopathy. Basically, when a protein that is spread across the brain has a prion, the brain can lose its very structure. If you've ever looked closely at a sponge and noticed all the little holes and bubbles, that is what the brain resembles under the microscope when it has been afflicted with "mad-cow". Hence the name, Spongiform.
There are a lot of varied types of prion disease, all extremely rare, some spectacularly rare (there is a book written by a member of one of the 30 estimated families carrying the Fatal Familial Insomnia gene, for instance, which they call the "family affliction"). All prion encephalopathies are fatal. There is simply no way we know of currently to halt their steady march through the brain. Thankfully, however, they are not exactly contagious. I say "not exactly" because there are incredibly perculiar circumstances in which they might spread in an individual case, but we would likely have bigger problems than one extra case of prion disease (I'm talking like, eating someones brain, but even then, you'd have to get the prion to reach the brain somehow, and yeah, I'm gonna stop there).
Why am I talking about Prions though? Well, there are some instances where FTD-presentations are in fact prion diseases underneath. This study (Yes, look at me, actually linking to the study) suggests that a fair few cases globally turn out to be prion diseases. There are diagnostic challenges to differentiating the two which the paper talks about, but I didn't quite get that far into it.
Look out for my coming post about Prions, it will be part of this Brain at the Brink series.
Parkinsons can also be misidentified - particularly in its early stages - as ADHD. ADHD is not a late-onset condition, it is incredibly unlikely for it to suddenly appear out of nowhere, and cases of it doing so would have to be linked to some kind of brain damage rather than a genetic factor. Parkinsons has similarities in this area because of the impact it has to dopaminergic neurons. While in ADHD, the problem is typically the ability for the dopamine to be kept around long enough at the synaptic cleft to transfer the correct signal, in Parkinsons, the dopamine is actually lacking, and not enough is there to start with to transfer the right signal.
Okay, back on topic...
So ultimately, FTD is either a gene mutation that affects the Tau protein microtubules, causing them to clump and tangle, or sometimes it is a prion disease which manifests similarly to genetic FTD. Which one Bruce has, I don't think anyone will ever know, and I don't think it's right to pry, but no matter what, it's gonna be a tough road ahead. Genetic diseases are equal-opportunity afflictions, striking the rich and poor, famous and private, big and small, black, white, male and female and everything in-between, and they can be incredibly tough to treat, and sometimes impossible to stop.
So how does any of this help?
Well, it doesn't, I don't think. Writing about it probably helps me more than anyone else. As a reforming hypochondriac, things like this scare the crap out of me, and I've found the only way to calm that fear is to study the subject of the fear itself in scientific detail.
I'm hopeful that someone else like myself might read this and feel a little better from it, and perhaps curious to know more. It might even encourage someone into the field of research for this and other rare conditions like it. I can only hope.
That's all from today's episode. If you enjoy the content, please like and subscribe, and better yet, encourage a friend to take a look too :) it’s free, so why not?