Neurodegenerative Disorder

Neurodegenerative disorders are chronic conditions that gradually damage and destroy parts of the nervous system, especially the brain, affecting more than 50 million people worldwide. While these conditions are permanent and incurable, many are now treatable thanks to medical advances, with current treatments focused on managing symptoms and slowing disease progression.

Table of contents

• What Are Neurodegenerative Disorders?
• Main Types of Neurodegenerative Disorders
• How Common Are These Conditions?
• Symptoms and Warning Signs
• What Causes These Conditions?
• Risk Factors
• Diagnosis and Testing
• Treatment Options
• Living With a Neurodegenerative Disorder

What Are Neurodegenerative Disorders?

Neurodegenerative disorders are conditions that gradually damage and destroy parts of your nervous system, especially areas of your brain. The term “neurodegeneration” refers to the gradual death of brain and nerve cells^[1][2].

Neurons are the building blocks of the nervous system, which includes the brain and spinal cord. These specialized cells normally do not reproduce or replace themselves. This means that when neurons become damaged or die, they cannot be replaced by the body^[7].

These conditions usually develop slowly, and the effects and symptoms tend to appear later in life. The term “neurodegenerative disorder” is not just a single type of condition. Instead, it is an umbrella term that applies to several types of conditions that share the common feature of progressive damage to the nervous system^[1][7].

Main Types of Neurodegenerative Disorders

Neurodegenerative disorders can be categorized based on their primary clinical symptoms, key genetic abnormalities, or anatomical locations of neurodegeneration. The main types include^[1]:

Dementia-type diseases cause progressive damage to various areas of the brain, causing neurons in several areas to die. This can cause a wide range of symptoms depending on brain areas affected. These conditions include Alzheimer’s disease, frontotemporal dementia, chronic traumatic encephalopathy (CTE), Lewy body dementia, and limbic predominant age-related TDP-43 encephalopathy (LATE)^[1].

Demyelinating diseases involve myelin damage or loss. Myelin is a protective covering around nerve fibers that helps with sending and relaying nerve signals. Examples include multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD)^[1].

Parkinsonism-type diseases happen because of damage to specific neurons in the brain that help manage coordination and precise control of muscle movements. This category includes Parkinson’s disease and other forms of parkinsonism, which is the general term for conditions that look similar to Parkinson’s^[1].

Motor neuron diseases happen when neurons that control movement die off. Examples include amyotrophic lateral sclerosis (ALS, often known as “Lou Gehrig’s disease”) and progressive supranuclear palsy (PSP)^[1].

Prion diseases are a type of protein misfolding disease that cause serious brain damage in a relatively short time. Most people with these conditions do not survive more than a year. Creutzfeldt-Jakob disease is the most common form. Most cases happen for unknown reasons, though it can also be genetic, with survival time for genetic cases ranging between one and 10 years^[1].

Other neurodegenerative conditions include Huntington’s disease, spinal muscular atrophy, and spinocerebellar ataxia^[7].

It is important to remember that there are many areas of overlap between the various neurodegenerative disorders. Many of them share symptoms and have causes that work similarly^[1].

How Common Are These Conditions?

Neurodegenerative disorders are uncommon, but happen often enough to be common knowledge. Researchers estimate they affect more than 50 million people worldwide^[1].

Most of these conditions are strongly connected to age and are much more likely to happen in people over 65. However, some conditions like Huntington’s disease and ALS often appear earlier^[1].

The World Health Organization (WHO) projects that the number of people over 65 will at least double in the next 30 years. This means the number of people with neurodegenerative conditions will also climb at a similar rate^[1].

In 2019, eighteen major neurological disorders collectively contributed to 10.06 million deaths and 349.22 million disability-adjusted life years globally, ranking second only to cardiovascular diseases (excluding stroke)^[13].

Symptoms and Warning Signs

The symptoms of neurodegenerative disorders vary widely. Some may have obvious connections to a neurodegenerative disorder, while other symptoms might seem completely unconnected without specific medical testing^[1].

In general, the different types of conditions cause the following symptoms:

• Dementia-type diseases cause confusion, memory loss, trouble thinking or concentrating, and behavior changes^[1]
• Demyelinating diseases commonly cause tingling or numbness, pain, muscle spasms, weakness and paralysis, and coordination issues^[1]
• Parkinsonism-type diseases cause uncontrollable trembling in the hands, legs, and arms, stiffness, loss of balance, and reduced mobility^[15]
• Motor neuron diseases affect neurons that control movement, leading to progressive weakness and mobility problems^[1]

With progression, these disorders can affect every aspect of a person’s life, including mobility and balance, abnormal movements, swallowing, bladder and bowel function, blood pressure fluctuation, sleep, breathing, heart function, memory and cognitive abilities, mood, and speech^[6].

Many neurodegenerative diseases have subtle signs, such as minor memory loss, that can sometimes be overlooked or perceived as natural symptoms of old age. However, despite their initially benign appearance, these diseases will cause extensive damage to the brain if left unchecked^[15].

What Causes These Conditions?

Most neurodegenerative disorders begin years or decades before symptoms are present. Research shows that in every neurodegenerative disease, there is an abnormal protein involved which becomes toxic to the nerve cells, resulting in cell death and cognitive decline^[8].

The main contributing factors to neurodegeneration are oxidative stress and inflammation. Oxidative stress is characterized by an excess of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and a decline in cellular antioxidant defense systems. This is the main cause of neuronal cell damage that results in neurodegenerative disorders^[13].

Different proteins are involved in specific neurodegenerative diseases^[8]:

• Beta-amyloid is a major protein involved in Alzheimer’s disease, but can also be present in Dementia with Lewy Bodies
• Tau protein, along with beta-amyloid, comprises Alzheimer’s disease pathology, but can also be present in other conditions
• Synuclein is a protein commonly seen in Parkinson’s disease, Dementia with Lewy Bodies, and Multiple System Atrophy
• TDP-43 is present in Amyotrophic Lateral Sclerosis (ALS) and some types of frontotemporal dementia
• Huntington protein is a mutated protein present in Huntington’s disease
• PrPSc is the primary protein in Creutzfeldt-Jakob disease

As the disease progresses, additional nerve cells can become overstimulated and die as well. With cell death, inflammation follows, causing further cell death. Ultimately, many factors contribute to disease progression in its later stages^[8].

Risk Factors

Several conditions and factors increase the risk for developing neurodegenerative disorders^[8]:

• Age is the strongest risk factor. Most conditions are strongly connected to age and are much more likely to happen in people over 65^[1]
• Cardiovascular disease
• Cerebrovascular disease
• Smoking
• Prior head injury, ranging from concussion to severe brain damage
• Genetics and family history
• Poor diet
• Sleep deprivation
• Alcohol use
• Depression

Research has shown that oxidative stress and inflammation are the two major contributing factors to neurodegeneration^[5].

Diagnosis and Testing

One of the best ways to manage these conditions is to learn about them and work with healthcare providers for accurate diagnosis. Well-educated patients are better able to manage their health and actively participate in their care^[16].

UT Southwestern and other major medical centers offer a multidisciplinary team approach that includes access to expert physicians, health care providers, leading research, and a complete array of neurodiagnostic tests to provide the most accurate diagnoses^[6].

Treatment for each neurodegenerative disease varies, and incorrect diagnosis may lead to treatment that is not helpful or could be detrimental. Consulting experts in the field with specialized training is necessary to ensure the correct diagnosis^[8].

Various diagnostic methods and tests are used to identify neurodegenerative disorders, including imaging tests, laboratory analysis, and physical examination. Research on the development of clinical predictions and classification algorithms using machine learning technologies creates new opportunities for early diagnosis and intervention^[9].

Treatment Options

Neurodegenerative diseases are incurable and debilitating conditions. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered incurable. However, many are now treatable thanks to medical advances^[1][5].

Currently, the main goal is to treat the symptoms and slow the progress of these conditions when possible. There are several medicines currently approved for managing neurodegenerative disorders, though a large majority of them only help with associated symptoms^[1][4].

Traditional treatments, such as cholinesterase inhibitors for Alzheimer’s disease or Levo-dopa for Parkinson’s disease, offer symptomatic relief but do not effectively address disease progression^[13].

UT Southwestern offers comprehensive, individualized treatment to help patients manage these complex neurological diseases. Their multidisciplinary team approach includes^[6]:

• Neurologists
• Physiatrists
• Physical therapists
• Speech pathologists
• Sleep specialists
• Urologists
• Otolaryngologists
• Psychiatrists
• Cardiologists
• Respiratory therapists
• Pulmonologists
• Psychologists
• Dietitians
• Social workers

Emerging therapies show promise for future treatment. Research into gene therapy, stem cell therapy, immunotherapy, and neurotrophic factors represents the forefront of neurodegenerative disorder treatment. Gene therapy applied to these conditions is a promising field of study that consists of modifying a patient’s genes to slow down disease progression^[12][13].

Viral vector-based gene therapy has shown promising results in spinal muscular atrophy, leading to research in the treatment of other neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. The US FDA recently approved three gene therapies for spinal muscular atrophy^[12].

Research also focuses on extracellular vesicles derived from mesenchymal stem cells as new strategies for treatment^[11][17].

Living With a Neurodegenerative Disorder

Many things change with the onset of a neurologic or neurodegenerative disease. With support, patients can influence the course of their disease and manage how they respond. You can live fully and have a neurologic disease^[16].

Keys to healthy living include several essential factors for healthy living and resilience^[16]:

Learn about your condition. One of the best ways to advocate for yourself is to do your homework and learn about your condition. Stick to national or international organizations for the most trusted information. If you don’t know where to look, ask a medical provider for a recommendation^[16].

Acknowledge losses. Cognitive functioning is often deeply tied to one’s sense of self and personal identity. There can be a lot to grieve, including career, community roles, relationships, and expectations for the future. Research has shown that working toward self-clarity after cognitive changes can ease the grief process and help move toward acceptance^[16].

Brain health. You can improve your brain’s resilience to a neurologic disease by attending to lifestyle factors that promote brain health. Research has shown that what you eat and drink, how much you exercise, how well you sleep, the way you socialize, and how you manage stress are all critically important to brain health^[16].

Compensatory skills and strategies. Neurologic conditions can change how you carry out simple and complex tasks. Learning new compensatory skills and strategies means re-learning how to focus, manage time, problem-solve, make decisions, and support memory. This can significantly improve how you live with cognitive changes^[16].

Relationships and connection. Individuals with neurologic conditions are at increased risk for cognitive decline if they become isolated. Talking openly about your neurologic condition, identifying new ways to connect, and coming up with ideas for how friends and family can be supportive are some ways to maintain relationships. A therapist or counselor can help. Many people also forge new relationships in support groups and communities^[16].

Valued living. Valued living means engaging in behaviors that are consistent with personal values. Research shows that people are happier and live better when they feel connected to their values. Higher levels of valued living have been linked with improved well-being, quality of life, better psychosocial functioning, and lower psychological distress in neurologic and other chronic health conditions^[16].

For caregivers, there are several ways to provide effective care without being overwhelmed^[15]:

• Be resourceful. There is a wealth of information available online to assist you and your loved one. Organizations like the Alzheimer’s Association, the Lewy Body Dementia Association, and the National Parkinson Foundation have resources and educational materials
• Connect with others. Having help and support from family, friends, and local support groups both online and in the community can be highly beneficial when making decisions about care

Through centers like the Peter O’Donnell Jr. Brain Institute at UT Southwestern, scientists are spearheading internationally recognized research to understand these devastating disorders. Clinicians and clinician scientists are involved in national and international research trials dealing with slowing the progression of neurodegenerative disorders as well as finding their causes, which can potentially lead to cures^[6].