What is leukoaraiosis (white matter disease)?

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From the Guidelines

Leukoaraiosis, also known as white matter disease, is a condition characterized by damage or deterioration of the brain's white matter, which contains nerve fibers (axons) that connect different brain regions, and is associated with an increased risk of incident stroke, mortality, and all-cause dementia, as reported in a recent meta-analysis and systematic review published in 2023 1.

Definition and Prevalence

White matter hyperintensities (WMHs) are a core feature of cerebral small vessel disease (SVD) and represent a key aspect of leukoaraiosis. According to the study published in Alzheimer's and Dementia 1, WMHs are increasingly prevalent through midlife and aging, with reports as high as 50.9% in ages 40 to 49 and 96.6% by ages 60 to 69.

Etiology and Pathology

The etiology of WMHs is not fully understood, but pathological examination reveals varying degrees of myelin loss, axonal rarefaction, edema, perivascular space dilation, gliosis, and microvascular disease, indicative of deteriorating white matter structure, as noted in the 2023 study 1. The primary causes of white matter disease include hypertension, diabetes, smoking, high cholesterol, and aging itself.

Symptoms and Treatment

Symptoms of white matter disease vary depending on the location and extent of damage but may include:

  • Cognitive decline
  • Balance problems
  • Difficulty walking
  • Urinary issues
  • Mood changes Treatment focuses on managing underlying conditions rather than the white matter changes themselves, with blood pressure control being crucial, typically aiming for readings below 130/80 mmHg using medications like ACE inhibitors, ARBs, or calcium channel blockers. Other important interventions include controlling diabetes, quitting smoking, maintaining healthy cholesterol levels, regular physical activity, and cognitive stimulation.

Management and Follow-up

While white matter changes cannot be reversed, progression can be slowed by addressing these risk factors. Regular follow-up with a healthcare provider is essential to monitor both the underlying conditions and any symptom progression, as emphasized by the findings of the 2023 meta-analysis and systematic review 1.

From the Research

Definition and Overview of Leukoaraiosis

  • Leukoaraiosis, also known as white matter disease, refers to the appearance of bright spots on magnetic resonance imaging (MRI) scans, indicating damage to the brain's white matter [ 2, 3 ].
  • These bright spots, or white matter hyperintensities (WMH), are associated with a range of vascular risk factors, including hypertension, diabetes, and stroke [ 4, 5, 6 ].

Vascular Risk Factors and White Matter Disease

  • Studies have shown that conventional cardiovascular risk factors, such as hypertension and diabetes, account for a significant portion of the variance in WMH volume [ 4 ].
  • However, a large portion of the variance remains unexplained, suggesting that other vascular and non-vascular factors may be involved in the development of WMH [ 4 ].
  • Hypertension, in particular, has been shown to be a strong indicator of the progression of WMH and associated functional decline [ 2 ].

Impact on Cognitive Function

  • White matter disease has been linked to impaired cognitive function, particularly in executive function, attention, and speed [ 3, 6 ].
  • Vascular risk factors, such as diabetes, hypertension, and stroke, have also been shown to independently influence neuropsychological performance, emphasizing the need to control these factors to prevent cognitive decline [ 6 ].

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cardiovascular risk factors and small vessel disease of the brain: Blood pressure, white matter lesions, and functional decline in older persons.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2016

Research

White Matter Hyperintensity-Associated Blood-Brain Barrier Disruption and Vascular Risk Factors.

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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