Neurodegenerative Disease

Original Editor - Lucinda hampton

Top Contributors - Lucinda hampton and Kim Jackson  

Introduction

Neurodegenerative disease is an umbrella term for a range of conditions which primarily affect the neurons in the human brain. Neurodegenerative diseases represent a major threat to human health. These age-dependent disorders are becoming increasingly prevalent, in part because the elderly population has increased in recent years.

• Neurons are the building blocks of the nervous system which includes the brain and spinal cord. Neurons normally don’t reproduce or replace themselves, so when they become damaged or die they cannot be replaced by the body.

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and / or death of nerve cells. This causes problems with movement (called ataxias), mental functioning (called dementias) and affect a person's ability to move, speak and breathe. Neurodegenerative disorders impact many families - these disorders are not easy for the individual nor their loved ones.

They are diverse in their pathophysiology. Examples of neurodegenerative diseases are:

• Alzheimer’s disease (AD) and other dementias
• Parkinson’s disease (PD) and Parkinsonism
• Prion disease
• Synucleinopathies
• Motor neurone diseases (MND)
• Huntington’s disease (HD)
• Spinocerebellar ataxia (SCA)
• Spinal muscular atrophy (SMA).

Epidemiology

In 2019, roughly 50 million people globally had a neurodegenerative disease, often resulting in dementia. This figure is predicted to rise to 152 million by 2060. These disorders are found among all age groups and in all geographical regions.

• The overall prevalence of neurodegenerative disease leading to dementia in Europe is 1.6% and 1% for males and females respectively in the 65-69 age class, rising to 11% and 12.6% in the 85-89 age class.
• A WHO report sends a clear message: unless immediate action is taken globally, the neurological burden is expected to become an even more serious and unmanageable threat to public health"

Etiology

• 
  Some neurodegenerative disorders are caused by inherited genetic changes. These disorders run in families: the faulty gene is transmitted from parents to their children.eg. Huntington’s disease, and rare cases of motor neurone disease and Alzheimer’s disease.
• The majority of neurodegenerative disorders are due to a combination of genetic and environmental factors. This makes it difficult to predict who will develop disease.
• Specific genetic changes that increase the chance of disease have been identified for some conditions, however in most cases the genetic influences on neurodegenerative disorders are not well understood.
• Environmental factors also contribute to neurodegenerative disorders. eg. There is evidence linking Parkinson’s disease with long-term exposure to pesticides, toxins and chemicals.
• The greatest known risk factor for many neurodegenerative disorders is age.
• In Australia there are more than 350,000 people living with dementia and around 80,000 people with Parkinson’s disease. These figures are likely to rise as the population ages, making neurodegenerative disorders a growing healthcare concern.
• In 2016, an estimated 5.4 million Americans were living with Alzheimer’s disease. An estimated 930,000 people in the United States could be living with Parkinson’s disease by 2020.

Pathology

Neurodegenerative disorders are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss because of metabolic or toxic disorders.

Neurodegenerative diseases can be classified according to

1. Primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease),
2. Anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations)
3. Principal molecular abnormality.

Molecular Abnormality

The most common neurodegenerative disorders are amyloidoses,

tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. The protein abnormalities in these disorders have abnormal conformational properties. Growing experimental evidence suggests that abnormal protein conformers may spread from cell to cell along anatomically connected pathways, which may in part explain the specific anatomical patterns observed at autopsy.

1. Amyloidosis
2. Tauopathies:
3. Synucleinopathies.
4. TDP-43 proteinopathies are a set of neurodegenerative disorders characterized pathologically by cytoplasmic inclusions composed of TDP-43. The pathology has been implicated in three major diseases ie.Motor Neuron Disease (vast majority of cases). Frontotemporal lobar degeneration. Limbic-predominant age-related TDP-43 encephalopathy (by definition; often diagnosed clinically as dementia of the Alzheimer type)

5. Prion Diseases

Diagnosis

Neurodegenerative diseases are often presented as a distinct entity, however there is often overlap as you may have noted in the above descriptions, eg for AD and Lewy body pathologies. None of the neurodegenerative disorders have perfect diagnostic accuracy, and neuropathology will continue to be the gold standard for the foreseeable future.

• Studying disease heterogeneity at autopsy is key to understanding discrepancies between clinical and pathological diagnoses. This is a critical concept because there are many efforts to develop biomarkers to diagnose these diseases and to monitor disease progression in clinical trials

Treatment

There are currently no drugs to prevent or cure neurodegenerative disorders.

• Medications to control symptoms can be very effective. Other approaches to manage symptoms and maintain daily activities include physiotherapy, speech pathology, occupational therapy and psychiatry. A multidisciplinary approach is typically applied to improve the quality of life for people with neurodegenerative disorders.
• Research is ongoing to find much-needed new treatments for neurodegenerative disorders. One of the most exciting treatments uses stem cells to replace the neurons that have died. With so many brilliant minds working on a cure, hopefully there will soon be help for people with these diseases.

Physiotherapy

Neurodegenerative disorders are a group of progressive neurological diseases that cause worsening motor, cognitive and autonomic dysfunction over time.

• Recent advances in international research, best-practice evidence, and clinical guidelines have underscored the role of physiotherapy in the management of neurodegenerative disorders.
• Physiotherapy guidelines based on systematic reviews of best available evidence have since been published for many of these conditions.
• Most patients are referred to physiotherapists for this treatment.
• See individual links for physiotherapy management.