Vascular dementia

Vascular dementia is a type of cognitive impairment caused by cerebral ischemia. Risk factors include advanced age, diseases associated with atherosclerosis, and certain genetic conditions (e.g., CADASIL). Cognitive decline and other clinical features may develop gradually and/or in a stepwise manner depending on the nature of the underlying vascular compromise. The clinical diagnosis is supported by evidence of cerebrovascular disease on neuroimaging and exclusion of other reversible causes of cognitive decline. Management includes supportive care and focuses on preventing further cerebrovascular damage through treatment of underlying conditions and antiplatelet drugs.

• Second most common type of dementia (occurs in 15–20% of individuals with dementia) ^[1]
• Prevalence increases with age.

Epidemiological data refers to the US, unless otherwise specified.

• Vascular dementia is caused by prolonged and severe cerebral ischemia, primarily: ^[2]
  • Large artery occlusion (usually causes cortical ischemia)
  • Lacunar infarcts (small vessel occlusion causing subcortical ischemia)
  • Chronic subcortical ischemia
• Risk factors ^[2][3]
  • Advanced age
  • History of stroke
  • Atrial fibrillation
  • Risk factors for atherosclerosis, e.g.:
    • Chronic hypertension
    • Diabetes mellitus
    • Hyperlipidemia
    • Obesity
    • Reduced physical activity
  • Genetic disorders (e.g., CADASIL) ^[4]

In individuals of advanced age, mixed dementia (e.g., Alzheimer disease with vascular dementia) is more common than one form of dementia alone. ^[5]

Lesions of the smaller (microangiopathy) and larger (macroangiopathy) cerebral arteries share common risk factors and pathological features but produce distinct clinical entities. ^[6]

Small vessel disease ^[6][7]

• Predominantly caused by lipohyalinosis (hypertrophy of the vascular media combined with lipofibrous deposition within the vascular wall ), microatheroma, and/or amyloid beta deposition of cerebral vessels → thickening of the intima and/or the vessel wall, inflammation, thromboembolism → vessel stenosis, occlusion or rupture → cerebral ischemia → VD ^[8]
• Mainly causes infarcts or chronic ischemia in subcortical white matter (e.g., internal capsule) and/or in small penetrating arteries (lacunes) → diffuse white matter disease (infarctions or chronic ischemia), subcortical lacunar infarct, or the combination of both (known as Binswanger disease, which has multiple synonyms)

Large vessel disease

• Primarily caused by atherosclerosis (risk factors include hypertension, diabetes, and hyperlipidemia) ^[6][8]
• Usually in the form of repeated cortical ischemic events → progressive damage to neural networks (multi-infarct dementia) ^[7]
• If the affected area is large and/or significant enough (strategic infarctions ), a single ischemic event may suffice to bring on VD (single-infarct dementia). ^[7]

Symptoms depend on extent, location, and severity of vascular compromise and may overlap with other clinical features of dementia. ^[3][9]

• Progression ^[3][9]
  • Gradual deterioration in small vessel disease
  • Sudden onset and/or stepwise deterioration in multi-infarct or poststroke dementia
• Subcortical features ^[3][9]
  • Reduced executive function and processing speed
  • Delayed word recall and loss of visuospatial abilities
  • Memory loss
  • Mood disorders (e.g., depression)
  • Behavioral changes (e.g., apathy)
• Cortical symptoms
  • Unilateral visual field defects
  • Hemiparesis
  • Babinski reflex
• Other symptoms
  • Clinical features of stroke by affected vessel ^[3][9]
  • Motor deterioration, dysphagia, dysarthria (late-stage features)
  • Clinical features of associated conditions (e.g., peripheral arterial disease, diabetes mellitus, hypertension) and their complications may manifest. ^[4]

Vascular dementia is a type of irreversible cognitive impairment caused by cerebral ischemia in individuals with cerebrovascular disease.

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) ^[10]
  • An inherited variant of diffuse white matter disease (mutation in the NOTCH3 gene)
  • Multiple strokes secondary to microangiopathy without a history of hypertension
  • Characterized by migraine headaches with aura

Approach ^[5]

• Perform an initial evaluation of major neurocognitive disorder.
• Perform a comprehensive clinical evaluation, including cognitive testing (e.g., Montreal Cognitive Assessment). ^[11]
• Diagnosis is based on the DSM-5 criteria for vascular neurocognitive disorders. ^[12]
• Consider referral for specialized neuropsychological testing if there is diagnostic uncertainty.

Diagnostic criteria ^[12]

Neuroimaging ^[3][13]

Neuroimaging can be used to establish the diagnosis of vascular dementia by confirming cerebrovascular disease and ruling out reversible or nondegenerative causes of cognitive decline (e.g., chronic subdural hematoma, normal pressure hydrocephalus).

• MRI brain
  • Preferred modality
  • More sensitive than CT for detecting small vessel disease
  • Findings include:
    • Multiple cortical infarcts
    • Subcortical (i.e., lacunar) infarcts
    • White matter lesions (periventricular and in the semioval center)
    • Microhemorrhages
    • Atrophy
• CT brain
  • Used to exclude alternative causes of cognitive decline
  • Findings include:
    • Microangiopathic lesions in white matter
    • Multiple subcortical lacunar infarcts
    • Established infarctions
    • Atrophy
• FDG PET-CT ^[4]
  • Not routinely performed
  • Can be used to distinguish between vascular dementia and Alzheimer disease
  • Findings include: focal cortical and subcortical hypometabolism

Additional studies ^[5]

Consider additional studies to evaluate for comorbidities and common reversible causes of cognitive impairment.

• Laboratory studies (e.g., TSH, vitamin B₁₂, HbA1c)
• Cardiovascular and peripheral vascular studies ^[5]
  • Carotid ultrasound
  • Echocardiography
  • 12-lead ECG

• Other dementia subtypes (e.g., Alzheimer disease)
• Parkinson disease
• Depression
• Metabolic or endocrine disorders (e.g., vitamin B₁₂ deficiency, hypothyroidism)
• Infections (e.g., neurosyphilis)
• Space-occupying lesions (e.g., brain tumors or chronic subdural hematoma)
• Multiple sclerosis

The differential diagnoses listed here are not exhaustive.

Management focuses on preventing further cerebrovascular damage and providing supportive care for patients with dementia (e.g., cognitive training).

• Manage related cardiovascular risk factors and disease, e.g.:
  • Management of ASCVD
  • Management of hypertension
  • Management of diabetes
  • Life's Essential 8 framework
• Consider secondary prevention for ischemic stroke (e.g., antiplatelet therapy).
• Consider antidementia medications only for patients with concurrent Alzheimer disease.
• Provide supportive management of patients with dementia.

Control of vascular risk factors earlier in life may help prevent vascular cognitive impairment and dementia. ^[4]