Excerpt from Vascular Dementia

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Background

Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. Vascular dementia is preventable; therefore, early detection and an accurate diagnosis are important.

Patients who have had a stroke are at increased risk for vascular dementia. Recently, vascular lesions have been thought to play a role in AD.

As early as 1899, arteriosclerosis and senile dementia were described as different syndromes. In 1969, Mayer-Gross et al described this syndrome and reported that hypertension is the cause in approximately 50% of patients. In 1974, Hachinski et al coined the term multi-infarct dementia. In 1985, Loeb used the broader term vascular dementia. Recently, Bowler and Hachinski introduced a new term, vascular cognitive impairment.

Pathophysiology

Many subtypes of vascular dementia have been described to date. The spectrum includes (1) mild vascular cognitive impairment, (2) multi-infarct dementia, (3) vascular dementia due to a strategic single infarct, (4) vascular dementia due to lacunar lesions, (5) vascular dementia due to hemorrhagic lesions, (6) Binswanger disease, (7) subcortical vascular dementia, and (8) mixed dementia (combination of AD and vascular dementia).

Vascular dementia is sometimes further classified as cortical or subcortical dementia.

Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Common areas of the brain associated with cognitive decline are the white matter of the cerebral hemispheres and the deep gray nuclei, especially the striatum and the thalamus. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. The 3 most common mechanisms of vascular dementia are multiple cortical infarcts, a strategic single infarct, and small vessel disease.

Mild vascular cognitive impairment can occur in elderly persons. It is associated with cognitive decline that is worse than expected for age and educational level, but the effects do not meet the criteria for dementia and are not associated with vascular risk factors or evidence of silent strokes or extensive white matter infarcts on CT scanning. These people have subjective and objective evidence of memory problems, but their daily functional living skills are within normal limits.

In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets.

In single-infarct dementia, different areas in the brain can be affected, which may result in significant impairment in cognition. This may be observed in cases of anterior cerebral artery infarct, parietal lobe infarcts, thalamic infarction, and singular gyrus infarction.

Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis.

Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. These lacunae are found more typically in the internal capsule, deep gray nuclei, and white matter. Lacunar state is a condition in which numerous lacunae, which indicate widespread severe small vessel disease, are present.

Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

In cerebral amyloid angiopathy–associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. In hereditary cystatin-C amyloid angiopathy, patients have recurrent cerebral hemorrhages before age 40 years that can lead to dementia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a rare autosomal dominant condition localized to chromosome arm 19q12 that affects small vessels supplying the deep white matter. Pathologically, multiple small infarcts are observed in the white matter, thalamus, basal ganglia, and pons.

Other less common syndromes may lead to vascular dementia. Rare arteriopathies such as inflammatory arteriopathy (eg, polyarteritis nodosa, temporal arteritis) and noninflammatory arteriopathy (eg, moyamoya disease, fibromuscular dysplasia) can cause multiple infarcts and can lead to vascular dementia. Hypoperfusion due to large vessel or cardiac disease can affect the watershed areas of the brain and lead to vascular dementia.

Leukoaraiosis greater than 25% is considered to be pathological. Subcortical vascular dementia is a diffuse small vessel disease with minimal or absent infarction with homogenous pathological and clinical features.^{1, 2}

Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia.

Autopsy studies have shown the association between AD and vascular lesions.³ Several recent studies also suggest that the risk of developing AD is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. Apolipoprotein E may play a role in AD and vascular dementia. Apolipoprotein E-IV also increases the risk of dementia in stroke survivors and is a strong risk factor for the development of cerebral amyloid angiopathy in patients with AD. In elderly individuals, many cases of dementia may be caused by the cumulative effect of cerebrovascular and Alzheimer pathology.

One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.⁴

Vascular cognitive disorder (VCD) is a new term used to describe a particular constellation of cognitive and functional impairment spectrum that ranges from vascular cognitive impairment (VCI) to subcortical vascular dementia, poststroke dementia, and mixed dementia.²

Frequency

International

• Vascular dementia is the second most common cause of dementia in the United States and Europe, but it is the most common form in some parts of Asia.
• The prevalence rate of vascular dementia is 1.5% in Western countries and approximately 2.2% in Japan.
• In Japan, vascular dementia accounts for 50% of all dementias that occur in individuals older than 65 years.
• In Europe, vascular dementia and mixed dementia account for approximately 20% and 40% of cases, respectively.
• In Latin America, 15% of all dementias are vascular.
• In community-based studies in Australia, the prevalence rate for vascular and mixed dementia is 13% and 28%, respectively.
• The prevalence rate of dementia is 9 times higher in patients who have had a stroke than in controls. One year after a stroke, 25% of patients develop new-onset dementia. Within 4 years following a stroke, the relative risk of incident dementia is 5.5%.

Mortality/Morbidity

• In patients with dementia who have had a stroke, the increase in mortality is significant. The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls.⁵
• Vascular dementia is associated with a higher mortality rate than AD, presumably because of the coexistence of other atherosclerotic diseases.

Sex

• The prevalence of vascular dementia is higher in men than in women.

Age

• Incidence increases with age.

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