White Matter Disease
White matter disease, also called leukoaraiosis or white matter hyperintensities, refers to changes in the white matter of the brain that appear as bright spots on MRI scans. White matter consists of nerve fibers (axons) coated with myelin that connect different brain regions, enabling communication between areas. These hyperintensities represent areas where the white matter has been damaged, typically due to reduced blood flow (ischemia) from small vessel disease. While small amounts of white matter changes are common and often benign in older adults, extensive white matter disease is associated with increased risk of stroke, cognitive decline, balance problems, and dementia.
What is it?
The brain consists of gray matter (nerve cell bodies) and white matter (nerve fibers connecting different brain regions). White matter gets its name from the white, fatty myelin sheath that insulates axons and enables rapid signal transmission. White matter disease represents damage to these nerve fiber pathways, appearing as hyperintense (bright) areas on T2-weighted and FLAIR MRI sequences. The damage occurs primarily through chronic ischemia—reduced blood flow from small vessel disease affecting the tiny arterioles that supply deep brain white matter. This leads to demyelination (loss of myelin), axonal damage, and eventually formation of small cavities or gliosis (scarring).
White matter changes are classified by location and severity. Periventricular white matter hyperintensities occur adjacent to the ventricles (fluid-filled spaces in the brain), while deep white matter hyperintensities are located further from the ventricles in the centrum semiovale and corona radiata. The Fazekas scale is commonly used to grade severity from 0 (no lesions) to 3 (extensive confluent lesions). Risk factors mirror those for vascular disease and include advancing age (the strongest predictor, with prevalence increasing dramatically after age 60), hypertension (high blood pressure), diabetes mellitus, high cholesterol, smoking, obesity, cardiovascular disease including atrial fibrillation, history of stroke or transient ischemic attack (TIA), chronic kidney disease, and possibly sleep apnea. Some white matter changes may also result from genetic conditions (such as CADASIL), demyelinating diseases (multiple sclerosis), or inflammatory conditions, though these are less common causes.
Important to Know
Many individuals with mild to moderate white matter disease have no noticeable symptoms, particularly in early stages. The changes are often discovered incidentally on brain MRI performed for other reasons such as headaches or minor head trauma. However, as white matter disease becomes more extensive, it can manifest through various symptoms including cognitive changes such as slowed thinking (bradyphrenia), difficulty with attention and concentration, executive dysfunction affecting planning and organization, and memory problems; gait and balance difficulties including unsteady walking, increased fall risk, and difficulty with complex movements; mood changes including depression and apathy; urinary urgency or incontinence; and increased stroke risk. It’s important to note that the correlation between imaging findings and symptoms is imperfect—some people with extensive white matter changes function normally, while others with moderate changes have significant symptoms. The clinical significance depends on the extent, location, and rate of progression of white matter changes, as well as other factors like brain reserve and cognitive resilience. Diagnosis is made through brain MRI, which clearly shows white matter hyperintensities. The distribution and pattern help distinguish age-related changes from other conditions. Additional testing may include cognitive assessment if symptoms are present, evaluation for cardiovascular risk factors through blood pressure monitoring, lipid panel, glucose testing, and screening for other conditions that might contribute. While there is no specific treatment to reverse existing white matter disease, management focuses on preventing progression through aggressive control of vascular risk factors: maintaining optimal blood pressure (target typically less than 130/80 mmHg), managing diabetes with target HbA1c under 7%, treating high cholesterol with statins if indicated, smoking cessation, regular physical exercise (both aerobic and strength training), maintaining healthy weight, heart-healthy diet such as the Mediterranean diet, and treating sleep apnea if present. Antiplatelet therapy (aspirin or clopidogrel) may be recommended for those with significant vascular disease. Cognitive stimulation and social engagement may help maintain cognitive function. The prognosis varies widely—stable or slowly progressive white matter changes in older adults may cause minimal functional impairment, while rapidly progressive or extensive white matter disease is associated with increased risk of stroke, vascular dementia, disability, and mortality. Regular follow-up and aggressive risk factor management offer the best opportunity to slow progression and maintain quality of life.