Rare dementia series: Corticobasal degeneration

One of the least understood rare forms of dementia is Corticobasal degeneration. Many people will have never heard of this type of dementia, including many clinicians and healthcare professionals. So, let’s explore Corticobasal degeneration. What type of dementia is it? And does it overlap with other dementias?

Let’s find out.

Corticobasal degeneration

Corticobasal degeneration is a very rare and complex form of dementia. The complexity stems from the fact that its clinical symptoms can overlap with many other dementias, which makes it very difficult to distinguish the ‘clinical presentation’ of corticobasal degeneration from other dementia. On top of that, the underlying proteins changes (pathophysiology) of corticobasal degeneration overlap as well with other diseases, making it again difficult to distinguish it from other related diseases. Welcome to the murky waters of corticobasal degeneration.

What does corticobasal degeneration mean?

The ‘cortico’ part refers to the cortical regions of the brain, which lie on the surface of the brain. By contrast, the ‘basal’ term in corticobasal degeneration refers to the basal ganglia, which lie deep in our brain. So, the term corticobasal means that the disease affects both the superficial (cortical) and deep (basal ganglia) areas of the brain. The term degeneration means that it is a progressive condition leading to a decline in structure and function in those brain regions.

Which roles do these superficial and deep brain regions have in our brain?

Brain regions involved

The cortical brain regions are mostly involved in our thinking abilities (cognition), behaviour and decision-making but we also have cortical brain regions for movement, sensation, including all our basic senses. The cortical brain regions are often considered to be the computing centre of the brain where all the sensory information is processed, evaluated and then actions or decisions are formulated. We can already see that referring to ‘cortical’ brain regions is very vague since it can mean that any brain region(s) might be affected by corticobasal degeneration and that is exactly the case. The cortical brain regions affected in corticobasal degeneration can differ from person to person, making the changes caused by eth disease highly variable, or in scientific speak, heterogeneous.

This contrasts with other dementias, such as Alzheimer’s disease or Frontotemporal Dementia, for which highly specific cortical brain regions are first affected in the disease. But that is not the case in corticobasal degeneration, since the cortical brain regions affected by the disease can differ from person to person. This means that the ‘cortical’ symptoms someone with corticobasal degeneration has can differ from the ‘cortical’ symptoms of another person with corticobasal degeneration. This symptom heterogeneity also means that a person with corticobasal degeneration can present with symptoms similar to other dementias, such as Alzheimer’s disease or frontotemporal dementia.

I hope you understand now why I mentioned ‘murky waters’ before – as it is indeed very murky for clinicians to make a diagnosis of corticobasal degeneration and for the people with the disease to get the ‘correct’ diagnosis and appropriate support if we are simply checking the ‘cortical’ symptoms.

How about the basal ganglia symptoms?

The ‘basal ganglia’ symptoms in corticobasal degeneration are a bit more specific than the cortical changes, however, even those overlap with other dementias, such as Progressive Supranuclear Palsy, Dementia with Lewy Bodies and other neurodegenerative diseases, such as Parkinson’s disease. The list of these diseases gives already away that the ‘basal ganglia’ symptoms in corticobasal degeneration are mostly related to changes to movement.

The basal ganglia sit deep in our brain and coordinate with the cortical movement regions all our movements, from the most subtle finger movement to large leaps with our legs, and everything in between. It would be beyond the scope of the article to explain how this network of cortical and basal ganglia brain regions initiates and coordinates our movement. Suffice to say, that it is an intricate interplay which, if it is dysfunctional has a severe impact even on our smallest movements.

What are then the symptoms of corticobasal degeneration?

Symptoms

We already know that movement symptoms are key for corticobasal degeneration but which specific ones?

First off, let’s s start with limb apraxia. Apraxia comes from Ancient Greek, ‘a’ = not & ‘praxis’ = action, meaning inaction. Even though this suggests that people cannot move their limbs at all, it actually means the inability to perform precise, voluntary actions. For example, people with corticobasal degeneration have difficulties combing their hair or brushing their teeth, as this requires quote precise movements. The other common symptom is that people have difficulty getting dressed as it requires again precise movement to get into sleeves or buttoning up shirts. Limb rigidity, the inability to completely relax our muscles, is another common movement symptom in corticobasal degeneration. Limb rigidity means that our muscles can feel ‘stiff’ all the time, even when we try to relax them.

Other movement symptoms are similar to Parkinson’s disease, such as bradykinesia (from Ancient Greek, ‘brady’ = slow, ‘kinesia’ = movement, meaning slow movements), as well as shaking of hands or feet – so-called tremor (from Latin ‘tremens’ to shake or tremble). Finally, many people have or develop problems with their walking gait, which becomes unsteady or have so-called postural instability, meaning their posture can become easily unstable. Both these symptoms make people with corticobasal degeneration more likely to fall, which can increase the risk of disease progression but also fractures and even death.

On a cognitive level, the most common cognitive symptoms in corticobasal degeneration are related to language symptoms. Now, language is a complex cognitive process, involving language production (speech), reception (understanding) and processing. In corticobasal degeneration is mostly the language production that is affected. The language symptoms can be very similar to a form of frontotemporal dementia called progressive non-fluent variant primary progressive aphasia – what a mouthful! The language symptoms are mostly characterised by the omission of occasional words or mispronunciation of words, leading the language to become more ‘agrammatical’. In the worst cases, the language symptoms can become so severe that people become mute.

Other cognitive symptoms can be highly variable, due to the variable changes to the brain in corticobasal degeneration. Remember from above that the disease can affect various cortical brain regions. Therefore, some people with corticobasal degeneration might have memory problems while others have no such changes. Or some people might have visual disturbances while others have no such symptoms. Very confusing indeed.

If there is one other common symptom that is present in corticobasal degeneration, then it is behavioural changes. People with corticobasal degeneration can have changes similar to behavioural variant frontotemporal dementia, such as personality changes, irritability, disinhibition, lack of social manners and apathy. It can make the distinction from frontotemporal dementia difficult, in particular, if the behavioural symptoms overshadow the movement symptoms and families often struggle to receive the right support for the unique combination of movement and behavioural symptoms. Behavioural symptoms are often also the most difficult to deal with since the person’s personality changes quite radically from who they were before. It is important to remember that the behavioural symptoms are caused by the changes to the brain by corticobasal degeneration and are not wilful changes by the person displaying them. This is an important distinction, as many families have the impression at the beginning that a person with the disease is ‘difficult’, as their personality has changed. But it is the disease that has their personality changed and this change is, therefore, beyond their control.

Pathology and treatments

The key change in the brain of people with corticobasal degeneration is the accumulation of a protein – tau. You might have heard of tau already in the context of other dementias, such as Alzheimer’s disease or Progressive Supranuclear Palsy and the changes in corticobasal degeneration are very similar, it is just slightly different forms of tau which distinguish the different dementias. As in the other tau-related dementias, the tau in corticobasal degeneration starts accumulating in the nerve cells of the brain, which becomes toxic to the nerve cell and the nerve cell eventually dies. However, not only one nerve cell is affected by tau accumulation, but instead, the tau accumulation seems to spread to neighbouring nerve cells affecting them and so on. It is not yet clearly understood why the tau accumulation spreads but it means that the disease takes hold of an increasing amount of nerve cells causing symptoms.

What about treatments for corticobasal degeneration?

Similar to other dementias, there is to date no disease treatment for corticobasal degeneration available. There are only symptomatic pharmacological and non-pharmacological treatments available. These treatments try to alleviate mostly the movement and behavioural symptoms in corticobasal degeneration. However, many people are not aware that the higher risk for falls poses a significant risk in the progression of corticobasal degeneration. In general, falls in older age and dementia are known to have devastating consequences for people, as they often lead to fractures and hospitalisation. But that is not all, falls can also lead to subsequent severe (not consequences), such as infections or delirium which can be fatal. Due to the gait and postural symptoms in corticobasal degeneration, even more, care should be taken for falls prevention, as it can have significant consequences on people’s health and even lifespan.

Where does this leave us?

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Summary

In summary, corticobasal degeneration is a rare and little understood dementia. Even specialists can often not agree as to whether a person has corticobasal degeneration or not while the person is living (the only definite proof, as for many dementias is a post-mortem analysis of the brain). In particular, the heterogeneity of symptoms makes corticobasal degeneration very difficult to spot or diagnose. Symptoms can be significantly different from individual to individual. This also means that the symptoms of corticobasal degeneration can overlap with other dementias, such as memory problems in Alzheimer’s disease and behavioural & language symptoms in frontotemporal dementia. It can often lead to contradicting diagnoses people might receive since the symptoms in corticobasal degeneration are not clear-but. Even the movement symptoms can overlap with other dementias and even Parkinson’s disease. Speaking of movement symptoms, people with corticobasal degeneration have a higher risk of falls compared to other dementias, mostly due to their postural instability. This should be taken very seriously since falls can lead to fractures and infections, which can be fatal. Overall, there is an enormous amount to do to understand better corticobasal degeneration. Not only will this allow to spot or diagnose people better but will also lead to better symptom management and treatments in the future.

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Links

• https://www.nhs.uk/conditions/corticobasal-degeneration/
• https://rarediseases.org/rare-diseases/corticobasal-degeneration/
• https://rarediseases.info.nih.gov/diseases/46/corticobasal-degeneration

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