Vascular Cognitive Impairment and Dementia

Vascular cognitive impairment and dementia typically results from multiple cerebral infarcts (or sometimes hemorrhages). Although each infarct may be only minimally symptomatic in itself, the combination of multiple infarcts can cause enough neuronal or axonal loss to impair brain function.

There are four major types of vascular cognitive impairment and dementias (1):

• Subcortical ischemic vascular cognitive impairment and dementia

• Multi-infarct dementia

• Poststroke dementia

• Mixed dementia

Subcortical ischemic vascular cognitive impairment and dementia is caused mainly by small vessel disease. Subcortical lacunar lesions may develop, as may white matter lesions, which are mainly subcortical. Subcortical ischemic vascular cognitive impairment and dementia may include

• Multiple lacunar infarction: Multiple lacunar infarcts occur deep within hemispheric white and gray matter.

• Binswanger dementia: This variant is associated with severe, poorly controlled hypertension and systemic vascular disease. It causes diffuse and irregular loss of axons and myelin with widespread gliosis, tissue death due to an infarction, or loss of blood supply to the white matter of the brain.

Multi-infarct dementia affects medium-sized blood vessels, leading to large cortical infarcts.

Post-stroke dementia is immediate and/or delayed irreversible cognitive decline that begins within 6 months after stroke.

Mixed dementia is characterized by both vascular cognitive impairment, dementia, and other coexisting pathology (eg Alzheimer disease, dementia with Lewy bodies).

Uncommon types of vascular cognitive impairment and dementia include the following:

• Strategic single-infarct dementia: A single infarct occurs in a crucial area of the brain (eg, angular gyrus, thalamus).

• Cerebral amyloid angiopathy: Clinical history includes slowly progressive cognitive decline, episodic transient focal neurologic episodes (so-called amyloid spells), and sudden-onset focal neurologic deficits secondary to cortical lobar intracerebral hemorrhages.

• Hereditary vascular dementia: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations in the NOTCH3 (NOTCH receptor 3) gene, which codes for a transmembrane receptor located on vascular smooth muscle cells. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is also a small vessel disease; it is caused by mutations in the HTRA1 gene.

Cerebral amyloid angiopathy (CAA) is the accumulation of beta-amyloid in cerebral blood vessel walls, which results in a high risk of intracerebral hemorrhages. CAA occurs in several types of hereditary disorders but usually occurs sporadically. Cognition can be normal; however, prevalence of CAA is much higher in patients with Alzheimer's disease than in the general population.

Symptoms and signs of vascular cognitive impairment and dementia are similar to those of other dementias (eg, memory loss, impaired executive function, difficulty initiating actions or tasks, slowed thinking, personality and mood changes, language deficits). However, compared with Alzheimer disease, vascular cognitive impairment and dementia tends to cause memory loss later and to affect executive function earlier. Also, symptoms can vary depending on where the infarcts occur.

Unlike other dementias, multiple-infarct dementia tends to progress in discrete steps; each episode is accompanied by intellectual decline, sometimes followed by modest recovery. Subcortical vascular cognitive impairment and dementia caused by small-vessel ischemic damage (which includes multiple lacunar infarction and Binswanger dementia) tends to cause small, incremental deficits; thus, the decline appears to be gradual.

As the disease progresses, focal neurologic deficits often develop:

• Exaggeration of deep tendon reflexes

• Extensor plantar response

• Gait abnormalities

• Weakness of an extremity

• Hemiplegias

• Pseudobulbar palsy with pathologic laughing and crying

• Other signs of extrapyramidal dysfunction

• Aphasias

Cognitive loss may be focal. For example, short-term memory may be less affected than in other dementias. Because loss may be focal, patients may retain more aspects of mental function. Thus, they may be more aware of their deficits, and depression may be more common than in other dementias.

Patients with CADASIL commonly present with cognitive impairment, migraine headaches, and/or stroke. CARASIL can cause alopecia and spondylosis. Age at onset varies.

• Generally similar to diagnosis of other dementias

• Neuroimaging

Diagnosis of vascular cognitive impairment and dementia is similar to the diagnosis of other dementias. A general diagnosis of dementia requires all of the following:

• Cognitive or behavioral (neuropsychiatric) symptoms interfere with the ability to function at work or do usual daily activities.

• These symptoms represent a decline from previous levels of functioning.

• These symptoms are not explained by delirium or a major psychiatric disorder.

Evaluation of cognitive function involves taking a history from the patient and from someone who knows the patient plus doing a bedside mental status examination or, if bedside testing is inconclusive, formal neuropsychologic testing.

Differentiation of vascular cognitive impairment and dementia from other dementias is based on clinical judgment. Factors that suggest vascular cognitive impairment and dementia (or Alzheimer disease with cerebrovascular disease) include the following:

• Imaging evidence of brain infarcts and other vascular brain damage

• Clinical features characteristic of vascular cognitive impairment and dementia (eg, prominent executive dysfunction, mild or absent memory loss)

• High Modified Hachinski Ischemic Score (if brain imaging is not available)

Confirmation of vascular cognitive impairment and dementia requires a history of stroke or evidence of a vascular cause for dementia detected by neuroimaging. If focal neurologic signs or evidence of cerebrovascular disease is present, a thorough evaluation for stroke should be done.

CT and MRI may show

• Bilateral multiple infarcts in the dominant hemisphere and limbic structures

• Multiple lacunar strokes

• Periventricular white-matter lesions extending into the deep white matter

• In Binswanger dementia, leukoencephalopathy in the cerebrum semiovale adjacent to the cortex, often with multiple lacunae affecting structures deep in the gray matter (eg, basal ganglia, thalamic nuclei)

• In CADASIL and CARASIL, diffuse white matter hyperintensities with ischemic lesions in subcortical regions, including characteristic involvement of the anterior temporal lobe

• In cerebral amyloid angiopathy, lobar hemorrhage, multiple cortical microhemorrhage or superficial siderosis

Key features can help distinguish Alzheimer disease from vascular cognitive impairment and dementia (see table Differences Between Vascular Cognitive Impairment and Dementia and Alzheimer Disease). The Hachinski Ischemic Score is sometimes used to help distinguish vascular cognitive impairment and dementia (mainly multi-infarct dementia) from Alzheimer disease when no brain imaging is available (1).

The diagnosis of CADASIL and CARASIL can be confirmed by genetic tests, which identify characteristic mutations of the NOTCH3 gene for CADASIL and HTRA1 gene for CARASIL. Sometimes a skin biopsy can be done instead to confirm the diagnosis of CADASIL.

• Safety and supportive measures

• Management of vascular risk factors, including smoking cessation

Safety and supportive measures for vascular cognitive impairment and dementia are similar to those of other dementias. For example, the environment should be bright, cheerful, and familiar, and it should be designed to reinforce orientation (eg, placement of large clocks and calendars in the room). Measures to ensure patient safety (eg, signal monitoring systems for patients who wander) should be implemented.

Troublesome symptoms can be treated.

Managing vascular risk factors (eg, hypertension, diabetes, hyperlipidemia) may slow the progression of vascular cognitive impairment and dementia and help prevent future strokes, which could cause more cognitive impairment. Management includes the following:

• Blood pressure control

• Cholesterol-lowering therapy

• Regulation of plasma glucose (90 to 150 mg/dL)

• Smoking cessation

Medications, such as cholinesterase inhibitorsN-methyl-d-aspartate) antagonist, may help slow the loss of cognitive function in patients with moderate to severe dementia and may be synergistic when used with a cholinesterase inhibitor.

The 5-year mortality rate for patients with vascular dementia is about 60%, which is higher than that for most forms of dementia, presumably because other atherosclerotic disorders coexist.