Vascular Cognitive Disorders

Historical Overview and Terminology

The long-standing concept of hardening of the arteries or cerebral atherosclerosis as a cause of senility was challenged in the 1960s by the neuropathologic studies from Newcastle-Upon-Tyne, England, which suggested that vascular dementia (VaD) was related to multiple brain infarctions exceeding a certain threshold and was distinct from AD as a cause of dementia. The concept was further elaborated in a 1974 paper, which stated that “…when vascular disease is responsible for dementia it is through the occurrence of multiple small or large cerebral infarcts.” This led to the widespread use of the term multi-infarct dementia (MID) as being synonymous with VaD. The last 2 decades have witnessed a major challenge to this narrow conceptualization of VaD, with an expanded concept that includes not only multiple cortical and/or subcortical infarcts, but also strategic single infarcts, noninfarction white matter lesions, hemorrhages, and hypoperfusion as possible causes of VaD.

The broader VaD construct was, however, also considered to be inadequate to represent the full spectrum of cognitive dysfunction of vascular origin for a number of reasons. First, the focus on dementia precluded the inclusion of milder forms of cognitive impairment that failed to reach the threshold of dementia but were nevertheless important, especially for prevention. Second, growing neuropathologic evidence has indicated that most dementias have a neurodegenerative, usually due to AD pathology, and vascular basis, and that these pathologies appear to act synergistically. Third, most diagnostic criteria for dementia required the presence of memory impairment ; this was at odds with the clinical experience of the varied cognitive profile of VaD, with memory being relatively spared, especially in the early stages of the disease. This led to the introduction of the construct vascular cognitive impairment (VCI), which includes a broad spectrum of clinical profiles, from mild cognitive impairment to dementia, as well as individuals in whom cognitive impairment showed mixed primary neurodegenerative and vascular features or mixed features. The VCI construct provides a dimensional approach to cognitive impairment of vascular origin, recognizing that the impairment can range from mild to very severe. The underlying pathology is varied, including single strategic infarcts, multiple infarcts, and noninfarct white matter lesions or leukoaraiosis, hypoperfusion, or hemorrhage; the vascular lesions can coexist with other brain pathologies. It also affords greater attention to opportunities for primary and secondary prevention.

The VCI construct is not without its limitations. The term impairment is used in medicine to indicate a reduction or loss of function in any domain of functioning and is applied as a statistical construct based on normative data or demonstration of disability, but is not used to denote a disorder. Moreover, VCI has sometimes also been used in the literature to denote mild cognitive impairment (MCI) due to vascular factors, equating VCI with vascular MCI. Hence, the use of VCD recognizes that there is often a need for a categoric diagnosis, which encompasses mild impairment, predementia, and dementia syndromes at the same time. It can embrace many syndromes and diseases and also acknowledges the fact that patients with CVD also have noncognitive syndromes, such as depression, anxiety, and psychosis, which need to be distinguished from cognitive disorder. So-called functional impairment is seen as a consequence of the disorder. The use of the plural form, disorders, acknowledges that VCD comprises many diseases, each with varying severity and patterns of dysfunction.

Epidemiology

The prevalence and incidence of VCD vary, depending on the diagnostic criteria applied and the population studied. In 11 population-based European studies conducted in the 1990s, the age-standardized prevalence of VaD was estimated to be 1.6% compared to 4.4% for AD. The prevalence of VaD increased from 0.3% in those aged 65 to 69 years to 5.2% in those aged 90 years and older. VaD accounted for 15.8% of all cases of dementia in these studies. The Canadian Study of Health and Aging used a broader concept of VCI and estimated that approximately 5% of people older than 65 years had VCI, with 2.4% having VCI (not dementia), 0.9% having mixed dementia (vascular and neurodegenerative), and 1.5% having VaD. The incidence of VaD reportedly ranges from 6 to 12 cases/1000/year in those older than 70 years. The prevalence of VaD is much higher in poststroke patients, with 6% to 32% being reported in various clinical samples 3 months after a stroke. Dementia is 3.5- to 5.6-fold more frequent in stroke patients than in stroke-free controls. Poststroke dementia (PSD) has a complex cause, with a varying combination of large and small vessel disease, as well as nonvascular pathology such as AD contributing to the picture. Many stroke patients, up to 10% in some studies, have cognitive impairment sufficient to diagnose dementia prior to the stroke. In a longitudinal study, the 10-year risk of dementia after stroke was estimated at 19.3%, compared to 11.0% in nonstroke controls, suggesting that a stroke doubles the risk of incident dementia, although this excess risk diminishes with time and does not apply to those older than 85 years.

Vascular lesions are common in autopsy studies of dementia cases, with approximately one third showing significant vascular pathology, although this does not indicate the clinical relevance of such pathology. A review of pathologic studies, however, has shown a wide range in prevalence of VaD, from 0.03% to 85.2%, with a median figure of about 11%. Vascular brain lesions are also common in population-based autopsy series. In the U.S. Adult Change in Thought study, microinfarcts were common in nondemented (29%) and demented (63%) individuals, as were cystic infarcts (23% and 36% respectively), and the presence of two or more microinfarcts increased the risk of dementia 4.8 times (95% confidence interval [CI], 1.91 to 10.26). Other population-based neuropathologic studies have also highlighted the importance of vascular lesions, in particular microinfarcts, in the development of dementia. Consequently, VCD is generally referred to as the second most common form of cognitive impairment after AD.

Geographic variations in the prevalence of VCD have been noted, but the data are inconclusive. VaD was previously reported to be more common than AD in some Eastern Asian countries, but more recent data have shown a reversal. In the Hisayama Study from Japan, the incidence of vascular dementia was 12.2/1000 person-years for men and 9.0/1000 person-years for women, whereas for AD it was 5.1 and 10.9/1000 person-years, respectively. In the last 3 decades, the ratio of VaD to AD in Japan has shifted from 2 : 1 to 1 : 1, probably due to better control of vascular risk factors and stroke prevention. Reports from China have suggested a similar trend, with more recent studies reporting a higher prevalence of AD than VaD. Data from other developing countries are limited, but it has been suggested is that although AD is the most common cause of dementia, VaD is relatively more common than in industrialized countries.

Causes and Pathophysiology

Because the essential feature of VCD is that cognitive deficits are attributable to CVD, and the latter is extremely varied, the clinical manifestations and causes of VCD are very heterogeneous. One approach to the pathophysiology of VCD has been to examine the contributions made by large vessel disease, small vessel disease, noninfarct ischemic changes, and small and large hemorrhages. The parenchymal lesions associated with these factors are summarized in Table 53-1 .