What is the first-line treatment for cerebral small-vessel disease in an older adult (≥65 years) with white‑matter changes, lacunes, or vascular cognitive impairment?

Treatment of Cerebral Microvascular Changes

The first-line treatment for cerebral small vessel disease in older adults is intensive blood pressure control targeting systolic BP <120 mmHg, combined with comprehensive vascular risk factor management including statin therapy, diabetes control, and smoking cessation. 1, 2

Aggressive Blood Pressure Management

Target systolic BP <120 mmHg for patients over 50 years with BP >130 mmHg, as this approach reduces mortality, cerebrovascular events, and dementia/cognitive impairment with an absolute risk reduction of 0.4-0.7% per year. 1, 2 The relationship between blood pressure and vascular cognitive impairment is linear—lower is better down to at least 100/70 mmHg. 1

• Hypertension has the strongest evidence of association with poor cognitive performance and is the primary modifiable risk factor for small vessel disease progression. 1, 3
• The SPRINT MIND trial demonstrated that intensive BP control (goal <120/<80) significantly reduced the risk of mild cognitive impairment after a median of 5.11 years in patients aged ≥50 years. 1
• Home BP monitoring may provide more accurate assessment of control than office measurements. 3

Important caveat: The effects of intensive control to <120/<80 have not yet been trialed specifically in patients with prior stroke, though the evidence supports this target in the broader population with cerebral small vessel disease. 1

Comprehensive Vascular Risk Factor Control

Initiate statin therapy for LDL-cholesterol reduction in all patients with cerebrovascular disease unless contraindicated. 2

Optimize glycemic management with individualized HbA1c targets, as diabetes increases vascular cognitive impairment risk by 20-40%. 1, 2

Immediate smoking cessation is essential, with stroke risk declining to that of never-smokers within 5 years. 2

Aspirin 75-81 mg daily for secondary prevention in patients with established cerebrovascular disease. 2

Cognitive Screening and Monitoring

Perform formal cognitive testing focusing on executive function and processing speed, as these domains are most affected by white matter changes. 2 Beginning confluent or confluent subcortical white matter hyperintensities (Fazekas grade 2-3) are sufficient to cause clinical cognitive impairment in many individuals. 1, 2

Screen for neuropsychiatric symptoms including depression, anxiety, and apathy using validated tools, as these frequently coexist with cerebral small vessel disease. 1, 2

Consider referral to cognitive neurology if cognitive decline is detected on screening. 2

Pharmacological Management for Cognitive Symptoms

When cognitive impairment is present, consider cholinesterase inhibitors or memantine based on symptom severity:

• Donepezil 10 mg daily ranks first for improving cognition in vascular cognitive impairment, though it has the most side effects. 2, 4
• Galantamine ranks second in both efficacy and tolerability. 2
• Memantine (NMDA receptor antagonist) shows small improvements in vascular dementia. 2, 4

Important caveat: These medications provide only modest benefits and should not replace aggressive vascular risk factor management, which remains the cornerstone of treatment. 1, 5

Management of Neuropsychiatric Symptoms

Cognitive behavioral therapy improves mood, increases depression remission odds, and improves quality of life. 2, 4

Serotonergic antidepressants (SSRIs) significantly improve overall neuropsychiatric symptoms, agitation, and depression in individuals with vascular cognitive impairment. 4

Avoid antipsychotics except in extreme circumstances, as they carry increased risk of death primarily from cardiac toxicities. 4

Diagnostic Imaging Approach

MRI is strongly preferred over CT for investigating cerebral small vessel disease, as it is more sensitive to vascular changes like small brain infarcts. 1, 4

Core imaging sequences should include:

• Diffusion-weighted imaging (DWI) for acute changes 1
• Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensities 1
• Susceptibility-weighted imaging (SWI) or gradient echo (GRE) for microbleeds 1, 3
• T1-weighted and T2-weighted scans for structural assessment 1

White matter hyperintensities should be reported using the Fazekas scale, a validated visual rating system. 1, 2, 4

Radiology reports should follow STRIVE criteria (Standards for Reporting Vascular Changes on Neuroimaging) to standardize reporting of covert cerebrovascular disease. 1

Long-term Monitoring Strategy

Annual clinical assessment including cognitive screening, vascular risk factor review, and medication adherence. 2

Repeat MRI every 2-3 years or sooner if clinical decline occurs, to assess disease progression. 2

Encourage physical activity, Mediterranean diet, and cognitive engagement, though specific evidence for white matter disease is limited. 2

Critical Clinical Pitfalls to Avoid

Do not attribute all cognitive symptoms to cerebral small vessel disease alone—mixed pathology with Alzheimer's disease is extremely common, occurring in the majority of older adults with vascular changes. 1, 3

Do not delay treatment while waiting for symptom progression—the goal is prevention of further damage through aggressive risk factor control, not waiting for clinical manifestations to worsen. 1, 5

Do not use multiple CNS-active medications simultaneously (≥3 agents including antiepileptics) in older adults, as this significantly increases fall risk. 4