What Is White Matter Disease

  • Saba Amber BSc, Manchester Metropolitan University, UK
  • Geraint Duffy MSc, Medical Biotechnology and Business Management, University of Warwick, UK

Introduction to white matter disease

White Matter Disease is a general term for a number of diseases that impact the white matter regions of the brain. The diseases are caused by ‘lesions’ on areas of the brain that are made up of white matter. These diseases can have varying degrees of severity depending on the severity of the lesions and the condition of the white matter. Lesions in the brain’s white matter have a few different causes. The most common cause comes with ageing; the ageing brain may deteriorate, and lesions may form on the white matter, leading to the development of white matter disease. 

Anatomy of the brain and white matter

White matter refers to the regions of the brain that are bundles of myelinated axons.1 An axon is a long nerve fibre that is able to transfer electrical signals/impulses to other nerve cells in the brain and central nervous system (CNS). The axons are covered in a sheath of myelin (white in appearance, which gives white matter its name and is made up mostly of lipids), which insulates the axon and allows it to pass on the electrical impulses at a higher rate. The white matter is found deep in the core of the brain and connects the Grey Matter to other regions in the brain.2 The white matter allows the transfer of signals between the connected grey matter regions in the brain. 

Types and classification

White matter diseases that cause these white matter lesions can be split between vascular and non-vascular causes. Vascular white matter diseases affect the vascular system, conditions that damage blood vessels, which lead to reduced blood flow to the white matter of the brain. These can include:2

Due to reduced blood flow, the cells of the brain don’t receive the oxygen and nutrients they need to survive. This causes the areas of the brain affected to become ischaemic, leading to their death.

Non-vascular causes of white matter disease cover damage to the myelin sheath by causes other than preventing blood flow to these areas. They can be broken down into several subcategories, including:2

  • Inflammatory
  • Infectious
  • Certain cancers
  • Genetic

Another white matter disease is Leukoaraiosis, which is the abnormal appearance of the white matter in the brain. This is mainly found in older people and has been linked to ageing. But there are also vascular links to this, such as ischaemia (this is when there is not enough blood flow and oxygen reaching regions of the brain due to the narrowing of the blood vessels).2 This can cause damage to the white matter which is visible in imaging techniques such as MRI scans. Damage caused in this way tends to be irreversible

Causes and risk factors

Common causes of white matter disease

The causes of white matter disease depend on whether it is vascular or non-vascular. Vascular causes of white matter disease are most commonly a result of a stroke. Strokes resulting in white matter disease can be broken down into ischaemic and haemorrhagic strokes.

  • Ischaemic stroke: A result of blood flow to areas of the brain being restricted, resulting in insufficient oxygen and nutrients for cells to survive. Causes include atherosclerosis, vasculitis and blood clots formed within blood vessels, breaking free and getting stuck within blood vessels in the brain (embolism).
  • Haemorrhagic stroke: Blood vessels in the brain bulging and then rupture as a result of pressure build-up. Causes include high blood pressure and Amyloid Angiopathy. 

Non-vascular causes of white matter disease are more varied. They all involve the breakdown of myelin, although the causes can be broad, such as the immune system attacking myelin producing cells (Multiple Sclerosis),3 infectious pathogens infiltrating the CNS or genetic conditions that cause the myelin sheeth to degrade.4,5

Risk factors

There are certain risk factors that increase a person's chance of developing white matter diseases. This can include being above a certain age. Some damage to the brain’s white matter such as lesions are normal in people above the age of sixty however, problems occur when there is a large number of lesions present and they start to cause other symptoms like cognitive decline.2

Certain medical conditions can also increase the risk of developing white matter disease. This can include hypertension (high blood pressure), vascular conditions, depression, obesity and poor diet and lifestyle choices. In some cases, there are also links to genetics playing a part in developing white matter diseases as certain ethnic groups present a higher risk of developing white matter lesions- individuals from an Afro-Caribbean background have a higher risk when compared to individuals of a Caucasian background.6

Symptoms and clinical presentation

The symptoms of white matter disease can vary greatly depending on the severity of the disease, the area of the brain affected and the cause. The symptoms can be broken down into: 

Cognitive symptoms

One of the major symptoms of white matter disease is cognitive decline. This can include problems with memory, speech and focus. An individual may appear confused or unable to concentrate. This can be quite disruptive to an individual’s daily life. 

Physical symptoms 

Physical symptoms can include weakness in the muscles. Symptoms can manifest as stiffness and/or numbness and tingling in areas of the body. The individual may also have problems with their balance and coordination that may negatively impact their mobility. 

Emotional and psychological effects

Depending on the severity of the disease, the physical symptoms may be debilitating and result in a significant impact on an individual's day-to-day activities. They may be unable to do the things they once loved or take part in everyday activities due to physical limitations. This may be particularly distressing to active or independent individuals who did not require any help before their diagnosis. Furthermore, as the cognitive symptoms increase in their severity, the individual may feel alone and frustrated by their confusion and inability to concentrate on everyday tasks. These feelings of frustration and isolation can lead to cases of anxiety and depression, so it is very important to support your loved ones through their diagnosis. It is also important to seek help if you are feeling this way. 

Diagnosis and evaluation

The tests done to determine white matter disease can depend on whether there are any conditions linked with its development that have already been diagnosed, such as MS, atherosclerosis, prior strokes or certain genetic conditions.

Role of brain imaging

Brain imaging techniques such as MRI scans and CT scans are used to observe the brain and see the condition of the white matter regions. Lesions in the white matter regions are visible on such scans and can be used to diagnose the disease.

Neurological assessments and cognitive tests

Neurological and physical examinations can be done to find out the extent of the effects of any lesions found by brain imaging tests. These tests are repeated over time to determine the level of cognitive decline as well as measure physical attributes such as muscle strength, vision, reflexes, and balance. If there is concern about an individual’s cognitive abilities, it is important to be seen by a specialist to test this and possibly find a diagnosis for why there has been a change in cognitive abilities and rule out other conditions. 

Treatment and management

Treatment focuses on the condition causing the disease. This can include:2

  • Medication to help prevent strokes from occurring, such as those that reduce blood pressure, lower cholesterol, or prevent blood clots from forming within blood vessels.
  • Medications are used to treat infections so that they do not advance to damaging the white matter.
  • Medications used to manage the physical, mental and emotional symptoms of white matter disease
  • Other forms of therapy for treating the symptoms are cognitive behavioural therapy (CBT), physiotherapy, and speech and language therapy.  

Prognosis and long-term outlook

Variability in the progression of white matter diseases

The prognosis largely depends on the disease itself and how advanced it is when diagnosed. Because of this, prognosis can vary widely between the causes as well as individuals with the same condition. For vascular causes of white matter disease, the general rule of thumb is that the larger the diameter of the lesions, the faster the decline in cognitive ability towards dementia is. Additionally, the regions of the brain where the lesions are found can also influence prognosis, with lesions found in periventricular regions of the brain found to have worse cognitive decline and more falls than those with lesions of similar sizes in other areas of the brain.7 

For those with non-vascular causes of white matter disease, the prognosis can be far more than vascular. Progression can be sporadic or sudden, with gradual decline or periods of stability before further decline. It is important to discuss with your doctor how the underlying cause of white matter disease will affect you in the future, as well as how it progresses and what you can do to help slow its progression.  

When the white matter disease is caused by ageing-related causes, the disease and its symptoms are largely irreversible as the lesions in the white matter are not treatable.2 These types of diseases tend to get worse over time, and cognitive conditions tend to decline with time. 

Quality of life considerations

In cases of age-related white matter disease where there is no treatment available, the individual's condition is likely to deteriorate with time. After a certain period, the individual may require palliative care when they are unable to care for themselves to prevent complications. Although the link between white matter disease and cognitive decline is well understood, there is some evidence that white matter disease can lead to other conditions that are linked to the brain's grey matter, such as Alzheimer's disease.8

Living with white matter disease

There are charities and support groups that can offer aid, help and information for many of the conditions that cause white matter disease. These include but are not limited to:

There are also a number of NHS Foundation trusts that cover rare inherited forms of white matter disease that provide help and support while also providing assistance to local hospitals in the best ways to manage the condition.

Prevention and risk reduction

Some lesions in the brain are to be expected with age. Although some forms of white matter disease cannot be avoided (such as genetic causes), common causes of white matter disease, such as stroke, can be reduced by tackling the cause of stroke. This can be done by doing regular exercise and eating a healthy, balanced diet. If you suffer from obesity or hypertension, it is important to see your GP and to follow the treatment plan that has been prescribed for you. 


White matter disease is a collection of conditions that cause damage to the white matter areas of the brain. These conditions can be divided into vascular white matter disease (damage caused by conditions that affect the blood vessels in the brain) and non-vascular white matter disease (conditions not linked to the vascular system such as infection, genetic, inflammatory, etc).

Symptoms can vary, depending on the underlying cause, but commonly include difficulty with speech, memory and concentration, as well as causing mood swings and depression. It can also cause muscle weakness, which can hinder balance and coordination. It is diagnosed by brain imaging tests to find any damage to the white matter of the brain. Other tests, such as blood tests, may be done to find out the underlying cause of the white matter damage.

Unfortunately, there is no cure for white matter disease, and treatment revolves around managing the symptoms it causes as well as preventing the condition from worsening.


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  2. Marek M, Horyniecki M, Frączek M, Kluczewska E. Leukoaraiosis – new concepts and modern imaging. pjr [Internet]. 2018 [cited 2023 Sep 20];83:76–81. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047080/ 
  3. Grueter BE, Schulz UG. Age-related cerebral white matter disease (Leukoaraiosis): a review. Postgraduate Medical Journal [Internet]. 2012 Feb 1 [cited 2023 Sep 20];88(1036):79–87. Available from: https://academic.oup.com/pmj/article/88/1036/79/6986734
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  7. Tafti D, Ehsan M, Xixis KL. Multiple sclerosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 13]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK499849/
  8. Hildenbrand P, Craven DE, Jones R, Nemeskal P. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol [Internet]. 2009 Jun [cited 2024 Jan 13];30(6):1079–87. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051319/
  9. Lamichhane A, Rocha Cabrero F. Metachromatic leukodystrophy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 13]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK560744/
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  11. Dhamoon MS, Cheung Y, Bagci A, Alperin N, Sacco RL, Elkind MSV, et al. Periventricular white matter hyperintensities and functional decline. J American Geriatrics Society [Internet]. 2018 Jan [cited 2024 Jan 13];66(1):113–9. Available from: https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.15149
  12. Kao YH, Chou MC, Chen CH, Yang YH. White matter changes in patients with alzheimer’s disease and associated factors. J Clin Med [Internet]. 2019 Feb 1 [cited 2024 Jan 13];8(2):167. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406891/
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Saba Amber

Medicinal and Biological Chemistry- BSc, Manchester Metropolitan University

Saba is a recent graduate in Medicinal Biochemistry with a particular interest in pharmacology.

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