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VARICOSE VEINS

See VASCULAR DISEASE

VASCULAR DEMENTIA

Introduction

Vascular dementias (VaDs) are the second most common causes of dementia, but much still needs to be done to sort out some basic ideas about how to describe the area. In the first instance, vascular dementias (the plural is used because unlike, say, Alzheimer’s disease, there is clearly more than one type) are related to cerebrovascular disease. Cerebrovascular disease, however, is also related to Alzheimer’s disease (AD) so that vascular factors are cognitive impairment world-wide (Hachinski).

Historic and conceptual context

As early as 1896 ‘‘arteriosclerotic dementia’’ (referring to VaD) was separated from ‘‘senile dementia’’ (referring to AD). Nevertheless, until the 1960s and 1970s cerebral atherosclerosis by chronically impairing blood supply to the brain was thought to be the commonest cause of dementia, and AD was regarded as a rare cause affecting only younger patients. Tomlinson et al. (Tomlinson, Blessed, and Roth) rediscovered AD as the more frequent cause of dementia than that of arteriosclerotic dementia. In 1974 Hachinski and colleagues used the term multi-infarct dementia (MID) to describe the mechanism by which they considered VaD was produced (Hachinski, Lassen, and Marshall). As the pendulum swung in the direction of AD, vascular forms of dementia became relegated to a position of relative obscurity.

Until the 1990s, the concept of VaD has been dominated by MID, i.e., a dementia caused by small or large brain infarcts. VaD has come full circle to be understood as cognitive impairment caused by chronic ischemic with or without stroke.

Epidemiology

With the varying conceptions of vascular dementia, one understanding of epidemiology has been affected by variations in the definition of the disorders, the clinical criteria used, and the clinical methods applied.

Prevalence. VaD is the second most common single cause of dementia, accounting for 10 to 50 percent of the cases, depending on the geographic location, patient population and clinical methods used (Hebert, Brayne; Lobo et al.). The prevalence of VaD seems to be higher in China and Japan than in Europe and North America. In a recent European collaborative study using population-based studies of persons aged sixty-five years and older conducted in 1990s the age-standardized prevalence of dementia was 6.4 percent (all causes), 4.4 percent for AD and 1.6 percent for VaD (Lobo et al.). In this study 15.8 percent of the cases had VaD and 53.7 percent AD. As expected, a large variation in VaD prevalence was seen across studies. The prevalence ranged from 0.0 percent to 0.8 percent at age sixty-five to sixty-nine years, and from 2 percent to 8.3 percent at age ninety years and over in different studies. There was a difference in prevalence between men and women; under eighty-five years of age the prevalence of VaD was higher in men compared to women and thereafter the prevalence was higher in women.

Incidence. The incidence of VaD has varied between six to twelve cases per year in one thousand persons aged seventy years and older (Hebert and Brayne). The incidence of VaD increases with increasing age, without any substantial difference between men and women.

Prognosis. The mean duration of any VaD is around five years (Hebert and Brayne), and their survival is less than for the general population or AD. Post-stroke dementia is an independent predictor of mortality.

Post-stroke dementia

Recent studies from around the world have shown that CVD increases the risk of dementia. The risk is higher than those associated with any other known risk factor for dementia.

Etiology and pathophsyiology

VaD as a clinical syndrome relates to different vascular mechanisms and changes in the brain, and has different causes and clinical manifestations. As noted, VaD is not only the traditional dementia of multiple strokes (Erkinjuntti and Hachinski, 1993; Chui). The pathophsyiology of VaD incorporates interactions between vascular etiologies (CVD and vascular risk-factors), changes in the brain (in strokes, white matter lesions and atrophy), host factors (age, education) and cognition (see Figure 1).

Etiologies of VaD include both CVDs and risk factors (see Table 1). The main CVDs include large artery disease, cardiac embolic events, small vessel and hemodynamic mechanisms.

Risk factors for VaDs (see Table 1) include risk factors for CVD, stroke, white matter lesions, but, at the same time, also those of any cognitive decline and AD (Skoog).

Many changes in the brain are associated with VaD including several types of strokes, white matter lesions, and incomplete ischemic injury (occurring when brain cells are injured by chronic low blood flow to the brain.

Heterogeneity of vascular dementias

As reviewed, VaD is not a distinct disease, but a group of more or less heterogeneous syndromes. One way to clarify this heterogeneity is to study possible clinical subtypes. Subtypes of VaD included in current classifications are cortical VaD (or MID), the subcortical VaD (small vessel dementia) and hypoperfusion dementia. Further subtypes suggested include hemorrhagic dementia, hereditary vascular dementia, and combined or mixed dementia (AD with CVD).

Main subtypes of vascular dementia

Cortical VaD (MID) is seen in connection with large vessel disease, cardiac embolic events and also hypoperfusion (see Table 2). It shows predominantly cortical and cortico-subcortical arterial territorial and distal field (watershed) infarcts. Typical clinical features are changes in strength or sensation on one side of the body, with facial problems such as language impairment, comprehension, and abrupt onset of cognitive impairment.

Strategic infarct dementia. Focal, often small, ischemic lesions involving specific sites critical for higher cortical functions are usually classified separately from other types of VaD. A stroke in one specific area, known as angular gyrus can give a syndrome almost indistinguishable from Alzheimer’s disease, except that it has a sudden onset. Subcortical infarcts can also give rise to dementia. Depending on the strategic location in question, the time-course and clinical features vary greatly.

Subcortical VaD. This type of VaD incorporates two entities ‘‘the lacunar state’’ and ‘‘Binswanger disease.’’ It relates to small vessel disease and is characterized by lacunar infarcts, focal and diffuse ischemic white matter lesions, and incomplete ischemic injury.

Ischaemic lesions in substantial VaD affect not only the subcortical areas, but also their link to prefrontal cortex. Indeed, the so called ‘‘subcortical syndrome’’ is its primary clinical manifestation. This syndrome includes several factors, such as weakness without sensory changes, motor difficulties with speech and swallowing, a gait disorder, depression and emotional liability, and, especially, deficits in executive functioning. Patients with subcortical VaD often have multiple lacunes and extensive white matter lesions on neuroimaging often do not give a clinical history characteristic to stroke.

Mixed dementia

The so-called ‘‘mixed dementia syndrome’’ (which usually refers to the combination of Alzheimer’s disease and VaD) may have been underrepresented in our estimation of dementia subtypes. VaD and AD seem to be more closely linked than might be explained on the basis of coincidence. Several vascular risk factors related to VaD have been shown also to be risk factors of clinical AD. In addition, infarcts and WMLs relate to an earlier clinical manifestation of AD. Further VaD and AD also share common pathogenic mechanisms such as delayed neuronal death and apoptosis. Overlap of these two mechanisms relate especially to the late-onset AD.

Clinical recognition of patients with mixed dementia or AD with CVD can be a problem. These patients can give a clinical history and signs of CVD, in this respect being clinically closer to VaD. On the other hand, many patients with AD are only found to have ischemic features in the neurophosis. In search of the therapeutic approaches however, we may have to choose a new focus. Instead of being prisons of old diagnostic dichotomies (pure AD vs. pure VaD), we should change the focus on etiopathogenetic factors, measure both the vascular burden of the brain, as well as the Alzheimer burden of the brain, and their consequences.

Clinical features of subcortical and cortical VaD

The early cognitive syndrome of subcortical VaD is characterized by (1) dysexecutive syndrome including slowed information processing, (2) memory deficit (may be mild), and (3) behavioral and psychological symptoms. The dysexecutive syndrome in subcortical VaD includes impairment in goal formulation, initiation, planning, organising, sequencing, executing, setsifting and set-maintenance, as well as in abstracting. The memory deficit in subcortical VaD is often mild. Sometimes it is manifested by impaired recall but relatively intact recognition. In consequence, patients often benefit from cues. Mild disorders are also commonly seen in subcortical VaD as is incontinence.

Clinical neurological findings especially early in the course of subcortical VaD include mild upper motor neuron signs, gait disorder, imbalance and falls. Often, however, these focal neurological signs are subtle or even transient.

By contrast, patients with cortical VaD, more commonly exhibit the neurological signs classically associated with stroke.

Onset and course. In subcortical VaD, the onset is variable, whereas in cortical VaD, it is typically sudden, with a step-wise deterioration following.

Diagnostic criteria

Several sets of clinical criteria for VaD have been used. The two cardinal components of all clinical criteria for VaD are the definition of dementia, and the definition of a vascular cause.

Each of the sets of clinical criteria are consensus by symptom experts, compared with criteria based on experimental studies. Each is based on the MID model of VaD.

Differential diagnosis

The differential diagnosis of VaDs include a number of conditions (see Table 3), but chiefly AD.

In consequence, the focus in a clinical diagnosis of AD has been on early episodic memory impairment, followed by often cognitive features, with a progressive course, with progressive dependence in function. This picture is distinct from early classical VaD.

In its classical conceptual form, probable VaD is characterized by an abrupt onset, a fluctuating and stepwise course, signs of cerebrovascular disease and ischemic lesions on brain imaging. By contrast, AD is characterized by an insidious onset, progressive course, without clinical signs of CVD and without signs of CVD in brain imaging.

AD and CVD (Mixed dementia). The issue of mixed dementia is a challenge. Increasing evidence shows that different vascular factors are related to AD, and frequently CVD coexists with AD. This overlap is increasingly important in older populations. Clinical recognition of patients with mixed dementia or AD with CVD, however, is a problem. As detailed in the neuropathological series of Moroney et al., these patients have a clinical history and signs of CVD, being clinically closer to VaD. In fact, in this series, fluctuating course (OR 0.2) and history of strokes (OR 0.1) were the only items differentiating AD from the mixed cases.

Problematic clinical examples include stroke unmasking AD in patients with post-stroke dementia, insidious onset and/or slow progressive course in VaD patients, and cases where difficulty exists in assessing the role of less extensive WMLs or of distinct infarcts on neuroimaging. This clinical challenge may be solved when a sensitive and specific ante-mortal marker for AD is available, and the distinction between AD and VaD could be supported by more detailed knowledge on which site, type and extent of ischemic brain changes are critical for VaD and which extent and type of medial temporal lobe atrophy specifies AD.

Prevention and treatment of vascular dementia

Primary prevention aims to reduce the incidence of a disease by eliminating its causes or main risk factors. In VaD dementia the targets are CVD, including arterial hypertension, atrial fibrillation, myocardial infarction, coronary heart disease, diabetes, generalized atherosclerosis, lipid abnormalities and smoking. In addition, the use of estrogen, anti-inflammatory agents and antioxidants appear to reduce the risk of VaD.

Secondary prevention aims to prevent established disease from progressing. It emphasizes early detection and treatment. Treatment is aimed at treating the underlying cause, such as large artery disease (e.g., aspirin, dipyridamole, clopidragril, carotid endarterectomy), cardiac embolic events (e.g. anticoagulation, spirin), small-vessel disease (e.g. antiplatelet therapy as in large vessel disease), and hemodynamic mechanisms (e.g. control of hypotension and cardiac arrythmias).

How well all this works still is unclear. While a considerable degree of progress in our understanding of vascular dementia has been made, it is clear that much needs to be done before we will have effective treatment of this common and disabling problem.

TIMO ERKINJUNTTI KENNETH ROCKWOOD

BIBLIOGRAPHY

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