Corticobasal Degeneration (CBD)
Corticobasal Degeneration (CBD) is a neurological disease that affects the area of the brain that impacts limb movement, speech, sensory perception and other movement functions. CBD is commonly referred to as an “atypical parkinsonism” because of its overlap of certain symptoms with Parkinson’s disease.
Quick Facts:
- Corticobasal degeneration (CBD) is a rare neurodegenerative disorder that has no known cause or cure.
- It affects brain cells that control limb movement, speech and other movement functions.
- On average, symptoms begin in the early 60’s, but may start as early as in the 40’s.
Symptoms of CBD:
With CBD, movement symptoms start on one side of the body and spread to the other side over time. Symptoms include:
- Stiffness, shakiness or jerky movements
- Slowness and clumsiness
- Walking and balance difficulty
- Difficulty controlling the muscles of the face and mouth (called dysarthria)
- Difficulty with speech generation (called dysphasia)
- Difficulty with articulation (called aphasia)
- Memory or behavior problems
Prevalence:
CBD is very rare and there are only 2,000 to 3,000 people diagnosed in the United States. These numbers are likely underestimates because of those who have not yet been accurately diagnosed.
In comparison, about 1 million people in the U.S. have Parkinson’s disease, and about 7 million have Alzheimer’s disease.
CBD and Other Brain Disorders:
Parkinson’s disease: CBD usually features little to no tremor compared to Parkinson's disease.
Progressive supranuclear palsy (PSP): People with CBD usually only have mild problems with balance and eye movements, while those are prominent symptoms of PSP.
Alzheimer’s disease: CBD has a similar pathology to Alzheimer's disease. However, dementia in CBD does not feature memory issues like those seen in Alzheimer's. Instead, dementia in CBD features slowness of thought, difficulty organizing thoughts and trouble resisting impulses. In addition, if dementia does occur, it tends to happen later in the disease.
What is CBD?
Corticobasal degeneration (CBD), like other parkinsonsim disorders, is characterized by slowness, muscle stiffness, issues with complex movements, balance problems and sometimes tremor. CBD is almost always asymmetric, meaning it almost always affects one side of the body first, and that side remains more progressed than the other side. Common symptoms of CBD include: While these are some common symptoms of CBD, each person with the diagnosis will experience the disease differently. Not everyone who has CBD will have all of these symptoms, and each person will have their own severity of symptoms. Corticobasal syndrome (CBS) is the clinical diagnosis given during life, while the term CBD is increasingly being reserved for cases confirmed through autopsy. Because of this, people are increasingly using the term “CBS” in reference to living patients and “CBD” only in reference to autopsy-proven corticobasal degeneration. The term “syndrome” means a set of abnormalities that appear in the same person at the same time but may or may not be caused by the same underlying disease in every case. CurePSP resources are available to anyone with a CBS or CBD diagnosis, as symptom management techniques will work on symptoms just the same. At this time, there is no specific test to diagnose CBD. To diagnose CBD, a neurologist will gather a person’s medical history, including neurological symptoms, when they started, and how they impact the person’s everyday functioning. They will also perform a physical examination where they will evaluate how a person walks, speaks, and moves their eyes, feet and hands. Brain scans, such as magnetic resonance imaging (MRI), a computed tomography (CT) scan and positron emission tomography (PET) scan, can show an asymmetric loss of bulk or function in certain parts of the brain, usually asymmetrically, corresponding to the asymmetry of the outward signs and symptoms. The brain imaging is most useful in ruling out other conditions, such as stroke or multiple sclerosis. In some cases, a neurologist will gauge how someone responds to medications for Parkinson’s disease, which can also help a neurologist make a diagnosis of CBD. Many people with CBD face a long and confusing diagnosis journey, including a number of tests, specialists and diagnoses. It is our hope that better awareness of CBD, especially within the medical community, will lead to earlier and more accurate diagnosis. CBD affects several areas of the brain, including those responsible for coordinating mouth and tongue movements and motor planning. CBD can cause speech to be: These changes to speech and voice can be coupled with difficulty getting out thoughts or finding words, making communication quite challenging for many people with CBD. It can be helpful to work with a speech-language pathologist, especially one who is specialized in Parkinson’s disease and related disorders, to learn exercises and strategies to help people with CBD continue to communicate as much as possible. CBD affects swallowing by making it difficult to swallow on command and issues with throat, mouth and tongue coordination. This can make it more difficult to swallow, which increases the risk choking and the risk of food or liquids going into the lungs, called aspiration. In some cases, aspiration can lead to pneumonia. Swallowing issues also make it more difficult for people to eat and drink, and can cause involuntary dehydration or weight loss. Signs of swallowing dysfunction can include: Your doctor may recommend regular examinations of your swallowing function to make sure food and liquid are going down the right way. Additionally, speech-language pathologists can help assess swallowing function as well as provide recommendations for diet and lifestyle modifications and exercises for the throat in order to make swallowing easier and safer. There are different ways that PSP can affect cognition, and in different levels of severity. For many people who receive a CBD diagnosis, an initial concern is about developing dementia. To break it down, dementia is a term that refers to the loss of cognitive functioning to the extend that it impacts a person's daily life. There are different types and causes of dementia. In Alzheimer's disease, the most common cause of dementia, cognitive impairment is mostly in the area of memory. However, this is not the only form of dementia and does not automatically mean that people with CBD or related diseases will develop issues with memory. People with CBD tend to instead develop issues with processing and organizing thoughts, planning, multitasking, keeping attention and world-finding. People may even experience different types of dementia within CBD. Common cognitive issues that people with CBD might experience: Executive dysfunction: Difficulty with planning, organizing and problem-solving Aphasia: Difficulty finding words, expressing thoughts and understanding language. The severity can vary greatly, and for some, it can be an early symptom of CBD. Visuospatial: Impairments in the ability to understand surroundings spatially. Apraxia of speech: Difficulty with physically saying the words that the person is trying to say. Behavior: Some people with CBD will exhibit lack of behavioral restraint and may say or do inappropriate things that they would not normally do. CBD almost never runs in families. However, a variant in the gene on chromosome 17 that encodes the tau protein is a little more common in CBD than in the rest of the population. Called the “H1 haplotype,” it occurs in 92 percent of people with CBD and in 77 percent of the rest of the population. So the H1 haplotype is (nearly) necessary but far from sufficient to cause the disease. We’re still not quite sure how the H1 haplotype increases CBD risk. One possibility is that it simply increases the amount of tau produced, which causes that protein to stick together, even if it’s not misfolded. Another possibility, discovered only this year, is that it causes too many “methyl groups” to stick to the tau gene, which alters its function. A methyl group is simply a carbon atom with three hydrogens. It can be attached to large molecules including DNA. Methylation is a normal way for the cell to regulate the function of DNA, thereby affecting the function of genes without actually changing the content of the genetic code like ordinary mutations do. This is exciting because certain molecules that can be developed into drugs alter DNA methylation. A detailed analysis of the genetics of CBD was published in 2015 by an international group of researchers. The project was partly sponsored by CurePSP. It found five genetic variants to be associated with CBD in addition to the H1 haplotype in the gene for tau. One of these genes, called MOBP, is also associated with PSP. It is the blueprint for the manufacture of a protein in brain cells’ myelin sheath, which serves as a layer of electrical insulation on the wires connecting brain cells together. These findings await confirmation by other research groups using other methods. If these gene variants are confirmed, the next step will be to figure out how those errors damage the normal function of brain cells. Those insights, in turn, will provide new ideas for drug targets. In other words, once scientists work out which steps in the brain cells’ normal function become disordered as a result of these CBD-related gene variations, they will know where new drugs could be directed to prevent the process from proceeding further. Coupled with a test to detect CBD in its earliest stages, before it actually causes any disability, such a drug treatment would amount to a CBD prevention. The average age of symptom onset is in people's early 60's, but can begin as early as the 40's and into the 90's. Most people with CBD live five to ten years after symptom onset, but many live much longer. There is no clear gender bias in CBD It can take many years for people to receive a CBD diagnosis. This can be because it is often originally misdiagnosed as Parkinson's diseases because it often begins similarly to Parkinson's. People may experience general slowing of the body, stiffness and maybe even tremor or slurred speech. Sometimes CBD will begin with aphasia, which is difficulty producing or understanding language. A common early symptom that is not similar to Parkinson's is apraxia in one hand. Apraxia is the loss of ability to perform complex, familiar and previously learned movements. Examples of this include using utensils, buttoning a shirt or typing on a computer. As the disease progresses, people may develop dystonia, which is when limbs are held in an involuntary, fixed posture. Over time, apraxia and dystonia may get worse, and symptoms will spread to the other side of the body. It is usually at this point that the risk for falls becomes greater. There also can be increase slurring of speech and difficulty swallowing. Swallowing challenges might begin to post a risk for aspiration. Some people will develop difficulty with multitasking or organizing their thoughts and can lose some behavioral inhibitions, which is known as dementia. To learn more about what to expect as CBD progresses, check out CurePSP's "Stages of CBD" resource.
Disease Management
Building a support team is foundational to the quality of life for the person diagnosed and their loved ones. Your support team may consist of your family, friends, support group, religious community, healthcare team and anyone else who cares about you. Download: Supporting Someone Diagnosed Find the right medical team. Professionals that can help with symptom management, care planning and education may include: Consider other care options. There are many options to help people with CBD get the care they need. People find huge benefits to hiring help to provide in-home care, utilizing community-based services such as adult day centers and choosing between many types of long-term care facilities. These services can provide additional layers of support, including companionship or hands-on help for the person with CBD and assistance and respite for the family. Professional In-Home Care: Where to Start and What to Ask Understanding Professional Long-Term Care Connect with others who understand the experience. CurePSP has over 15 virtual national and international support groups, a vast network of regional support groups and music therapy and chair yoga sessions. Learn more about these great opportunities for community connection. In addition, CurePSP has Peer Supporters who are volunteers that have a direct connection to PSP, CBD or MSA and offer one-on-one emotional and practical support to individuals in the disease journey. Peer supporters can connect with people through phone, email or in-person meet-ups. Click here to find a Peer Supporter near you or to volunteer as a Peer Supporter. No matter how you find support, please remember that you do not have to navigate the PSP journey alone. Connect with CurePSP at info@curepsp.org to learn more about resources and support. For many people with a diagnosis of CBD, the journey to a diagnosis was long and confusing. It is common to have initially received a diagnosis of Parkinson’s disease because of the similarities in early symptoms. Carbidopa/levodopa: The most common medication given to people with Parkinson's that supplies dopamine to a part of the brain called the substantia nigra, which uses the medication to signal movement in the body. While the movement issues in Parkinson’s are mostly explained by damage in the substantia nigra, that area is only one of many affected areas in CBD. So, while the treatment works well for people with Parkinson’s, its benefit in CBD is unpredictable, usually modest and wears off after only a few years if there is any benefit. When taking carbidopa/levodopa for CBD, it is recommended to take a standard form of the drug, rather than the controlled- or extended-release version. People with CBD might need a high dose of the drug and should be closely monitored by the healthcare team to watch for signs of cognitive issues or dizziness. People with CBD should be started on a low dose and gradually increase it to test tolerance and effectiveness. If there is no change in symptoms in two weeks, the maximum dose has been reached or there are any negative reactions to the medication, the medication can be tapered off and discontinued. The most common side effects can include nausea and sleepiness and issues with low blood pressure. Other Parkinson’s medications and their possible effect on CBD symptoms: Amantadine: This might have some benefit with gait issues, even if carbidopa/levodopa did not. Its benefit does not usually last more than a few months but can be useful for a short period. For people with CBD, the dosage should not exceed 200mg per day because of potential cognitive side effects. Entacapone (Stalevo): Taken in conjunction with carbidopa/levodopa, entacapone slows down the rate at which dopamine is broken down. This will only have an effect for people whose symptoms show a clear response to carbidopa/levodopa and have a distinct medication wear off between doses. Dopamine receptor agonists: These drugs have no benefit in PSP beyond what carbidopa/levodopa can do. They are more likely to cause hallucinations, confusion, dizziness and nausea. Cholinesterase inhibitors: This class of medications has some benefit for cognitive loss in people with Parkinson’s or Alzheimer’s disease. With the possible exception of rivastigmine (Exelon), they have no benefit for people with PSP Muscle relaxants: Dystonic muscle spasms may potentially respond to muscle relaxants like cyclobenzaprine, baclofen or tizanidine. These medications may cause sleepiness. Levitiracetam: This medication is intended for seizures but may help with dystonic muscle spasms. Botulinum toxin (known as Botox): This is injected directly into overactive muscles or glands for blepharospasm (forced closure of the eyelids), excessive drooling, jaw clenching, involuntary bending or turning of the neck or limbs and other types of dystonia. The effect may take one to two weeks to start and should last two to three months before having to be repeated. Injections into neck muscles must be done with caution, as the fluid can spread into and weaken nearby swallowing muscles, which may already be impaired by the disease process. People with CBD and related diagnoses can greatly benefit from rehabilitation therapies. Rehabilitation therapies are individualized interventions to improve or maintain quality of life. For people with CBD and related diagnoses, physical therapy (PT), occupational therapy (OT) and speech-language therapy often help people maintain or prolong their abilities as the disease progresses. A physical therapist (PT) helps people with movement symptoms they are experiencing. This typically looks like going through exercises during appointments that can help strengthen or correct movements that are important for balance and coordination and then continuing them at home. People with CBD should begin to see a physical therapist when they notice changes in balance or are having more difficulty getting around. Reasons to see a physical therapist: An occupational therapist (OT) helps people continue doing tasks and activities that prolong independence and help maintain a sense of joy and meaning in their lives. Reasons to see an occupational therapist: A speech-language pathologist (SLP) works with people who are having issues with speech, swallowing and language. Their goals are to improve and prolong communication skills, assess and help adapt to swallowing changes. Reasons to See a Speech-Language Pathologist: A feeding tube can be a safe and helpful option for people with CBD who are experiencing difficulties with swallowing. A feeding tube can be considered when someone is no longer able to take in necessary amounts of nutrition and calories by eating or drinking. They can prevent unnecessary weight loss and decrease risk of breathing in food or drink, known as aspiration. Getting a feeding tube placed means different things to different people, and there is no one right answer to whether or not someone should get on placed. Take the time to consider whether or not a feeding tube is right for you, before you need it. A feeding tube may get placed in some cases of emergency hospitalization, and if this is not a desire of yours, then be sure to state that in any advance directives. How is a feeding tube placed? Feeding tube placement is a surgical procedure done by a gastroenterologist (GI). The patient can be awake, but sedated and it is often an outpatient procedure. How is a feeding tube used? Formula or pureed food is fed through the feeding tube into the digestive system through either a syringe or a feeding bag. There are many store-bought formulas available that provide necessary amounts of nutrition and calories. There is also the choice to make food at home using a blender. Some people choose to feed with both formula and pureed food. Water can also be given through the feeding tube, both for hydration and to keep the feeding tube clear of debris and blockages. In some cases, and only if discussed with the healthcare team, medication can be given through the feeding tube. When living with a serious and progressive disease, it’s normal to experience sadness, uncertainty and fear about what the future may hold. These are normal emotions to process after receiving a life altering diagnosis — it requires a lot of emotional and physical energy to continually adapt to physical and mental changes! Like all feelings, these emotions are often temporary. However, when these normal emotions regularly interrupt your daily life and prevent you from participating in activities that you previously enjoyed, this could be a sign of a mental health issue. The most common mood symptom for people with CBD is depression, and some people may experience anxiety or apathy. Possible medications for depression and anxiety for people with CBD: Always speak with your neurologist before starting a mood medication. Non-drug methods for improving mood: Urgent mental health support options:
Warning: Tricyclic antidepressants (TCAs) are often used to treat insomnia, headaches and pain in the general population. However, for people with CBD, TCAs can impact cognitive function and should be avoided. For headache, topiramate can be considered instead.
Science and Research
In people with CBD, some groups of brain cells break down and die off. Central to that process is the abnormal folding and clumping of a protein called tau, which is a normal component of the brain. Its job is to help maintain the microtubules, which are stiff rods that function as the brain cells’ internal transportation and skeletal system. It appears that the cells’ death is caused by the tau protein clumps themselves and not by the reduced availability of tau for its normal function. The clumps’ technical name is neurofibrillary tangles. We know several reasons why tau might misfold, but we don’t know which one(s) are relevant to CBD. Tau forms similar aggregates in about a dozen other diseases, including Alzheimer’s disease, PSP, chronic traumatic encephalopathy and about half of all cases of frontotemporal dementia. The specific disease depends on the chemical characteristics of the tau aggregate and which brain cells are involved. We don’t yet understand what determines these. The microscopic brain abnormalities of CBD can affect different parts of the brain, producing different sets of outward symptoms in different people. The first variant to be described in the medical literature is called corticobasal syndrome and is the most common. It affects about half of all people with CBD and is the archetype of CBD described above. About a quarter of people with CBD have an outward appearance that resembles the most common form of PSP, which features problems with balance, eye movement, speech and swallowing. Another 15 percent have frontotemporal dementia, with inappropriately uninhibited behavior and difficulty organizing thoughts. Then there are two rare forms, each accounting for about five percent of the total. One has a dementia similar to that of Alzheimer’s disease, with important problems with memory or spatial orientation. The other is a form of aphasia, which means a problem with language, in this case difficulty finding words and obeying rules of grammar. All of the forms of CBD at some point include, in almost all patients, a degree of “motor parkinsonism,” meaning stiffness, slowness, soft speech and reduction in facial expression, sometimes with balance difficulty and tremor. Not so far, but there are experimental trials for PSP, and the two diseases are very similar at the molecular level. As of now, anything that helps scientists understand PSP could also help with understanding CBD. One major issue with experimental drug trials for CBD is that there are often too few patients available. Another problem is that about half of the patients who have the outward corticobasal syndrome actually have corticobasal degeneration, so any benefit of a drug could be diluted by the non-CBD patients in the trial, creating a false-negative result. Furthermore, any positive result in such a trial could be explained by an effect in some of the non-CBD patients, a messy result that would not satisfy most researchers, drug companies or the FDA There is important research being done to look for genetic and environmental contributors to the cause of CBD, as well as research on tests that can lead to more accurate diagnosis and improved care of CBD. Many people with CBD find that participation in research is a meaningful way to help doctors and scientists understand, diagnose and treat CBD and related diseases. Additionally, participants in clinical trials may benefit from a new treatment that is not generally available and may receive detailed care and attention that is not part of routine medical care. CurePSP Genetics Program: In collaboration with Massachusetts General Hospital, the National Institutes of Health and Indiana University, CurePSP is hosting a program with the aim of collecting genetic data from those with a PSP, CBD or MSA diagnosis. Get involved at psp.org/genetic-program. Clinical trials: In the United States, clinical trials are listed on a website maintained by the National Institutes of Health, www.clinicaltrials.gov. You can enter “progressive supranuclear palsy” into the search box. You can also ask your neurologist if they are aware of studies in CBD or CBS or consult curepsp.org for that information. Brain Donation: Donating your brain to science can be a powerful contribution to the understanding of PSP and other neurodegenerative conditions. Each donated brain is also evaluated by a trained neuropathologist to confirm that the diagnosis of PSP was correct. Setting up brain donation needs to occur early, ideally months or even years prior to someone passing away. Visit www.psp. org/ineedsupport/braindonation to learn about CurePSP’s Brain Donation Assistance Program. Building Partnerships: CurePSP is working hard to build partnerships with pharmaceutical and biotechnology companies to develop interest and funding for the study of PSP and related diseases. Funding Research: Additionally, CurePSP funds research through various grant programs and supports collaborative research projects through its growing CurePSP Centers of Care network of medical centers across the United States and Canada.