From the Guidelines
Periventricular and subcortical white matter FLAIR hyperintensities on brain MRI in patients with memory concerns are often indicative of small vessel disease, which may contribute to cognitive impairment. These white matter changes represent areas of chronic ischemia, demyelination, or gliosis. The clinical significance depends on their extent, distribution, and the patient's age and risk factors. Mild white matter changes are common in older adults and may represent normal aging, while more extensive or progressive changes correlate with increased risk of cognitive decline, gait disturbances, and stroke.
Key Considerations
- The presence of lacunar infarcts or microbleeds suggests ischemic small-vessel disease, while confluent and symmetric white matter abnormalities may indicate genetic or metabolic leukodystrophies 1.
- Periventricular lesions with predominantly temporal pole involvement can suggest cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or other inherited conditions 1.
- MRI is preferable to CT for detecting vascular lesions in patients with dementia, and evidence for vascular abnormalities includes cortical or subcortical infarcts, leukoaraiosis or white matter T2 hyperintensity, microhemorrhages, and lacunar infarct 1.
Recommendations
- For patients with periventricular and subcortical white matter FLAIR hyperintensities, I recommend comprehensive vascular risk factor management including blood pressure control (target <130/80 mmHg), lipid management (statin therapy if indicated), diabetes control if applicable, smoking cessation, regular physical activity, and a Mediterranean-style diet.
- Cognitive monitoring over time is important to track any progression, and these interventions are recommended because small vessel disease is often progressive, and controlling vascular risk factors may slow progression and potentially preserve cognitive function.
- The presence of these white matter changes should prompt consideration of vascular cognitive impairment in the differential diagnosis of memory concerns, particularly when the pattern of cognitive deficits includes executive dysfunction and processing speed impairments alongside memory issues 1.
From the Research
Clinical Significance of Periventricular and Subcortical White Matter FLAIR Hyperintensity
- Periventricular and subcortical white matter hyperintensities (WMH) on MRI are associated with cognitive decline and increased risk of dementia 2, 3, 4
- WMH are a type of cerebral small vessel disease, which is a major risk factor for dementia and stroke 5
- The presence of WMH is believed to indicate some form of subcortical vasculopathy, and is associated with brain atrophy, executive function, mental processing speed, and verbal memory 3
Association with Cognitive Decline
- Periventricular WMH (pvWMH) are significantly correlated with medial temporal lobe atrophy (MTA) and Alzheimer's disease (AD) 2
- pvWMH are associated with semantic fluency, and assessment of semantic fluency may be useful for clinical evaluation of subcortical hyperintensity burden 2
- WMH burden is associated with cognitive decline, particularly in processing speed, and aspirin use may moderate this association 6
Imaging Patterns and Brain Atrophy
- WMH are associated with patterns of brain atrophy found in ageing and Alzheimer's disease, and contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia 4
- The SPARE-BA index, which captures age-related brain atrophy, is significantly lower in individuals with high WMH burden, indicating more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease 4
Risk Factors and Prevention
- Cardiovascular risk factors, such as hypertension, diabetes mellitus, and smoking, are associated with WMH volume 4
- Preventive strategies reducing the odds of developing cardiovascular disease and WMH could decrease the incidence or delay the onset of dementia 4
- Epigenetic and integrative cross-omics analyses have identified novel genes influencing WMH burden, which may be targets for treatment in Alzheimer's dementia 5