- Email: [email protected]
Vascular Cognitive Impairment
CHAPTER 55
Vascular Cognitive Impairment Vascular cognitive impairment (VCI) is a global diagnostic category applied to a heterogeneous group of cognitive disorders that share a presumed vascular cause. Note that it is an umbrella term, which includes several syndromes, and is not simply the vascular counterpart of mild cognitive impairment (MCI). Specifically, VCI includes vascular dementia (including poststroke and multi-infarct dementia), mixed primary neurodegenerative disease and vascular dementia, and cognitive impairment of vascular origin that does not meet dementia criteria (VCI-ND). VCI may be preventable, although the evidence for this is not as complete as it is for the prevention of stroke. Beyond prevention, specific treatment has shown limited efficacy. Updated clinical diagnostic criteria for VCI are needed, and clinical investigators now emphasize harmonized standards to study the clinical, neuropathologic, and neuroimaging manifestations of VCI in daily practice. This chapter builds on a recent review1 to outline the evolution of the VCI construct, presents current thinking regarding clinical diagnosis and the supportive role of neuroimaging, and addresses the challenges that will shape future developments in this area.
HISTORICAL OVERVIEW The conceptual prototype for VCI was “multi-infarct dementia” (MID),2 itself an improvement over “senile dementia due to hardening of the arteries.”3 Like many prototypes, MID was constructed with inefficient tools: neuropsychological testing based on the Alzheimer’s disease paradigm and (initially) no or rudimentary neuroimaging. This construct defined MID as dementia arising as a consequence of multiple strokes and was said to account for 15% of dementias.4 As neuroimaging techniques evolved, the array of vascular pathologies outgrew the MID construct, so the vascular dementia (VaD) construct (of which MID became a subtype) was created to allow more flexibility in the size and distribution of neuroimaging abnormalities (from single strategic infarcts to leukoaraiosis) related to the diagnosis.5,6 Like its forerunner, the VaD construct was soon outgrown due to at least three key developments. First, growing neuropathologic evidence indicated that most dementias have both neurodegenerative (most commonly Alzheimer disease [AD]) and vascular features7 and that these features appear to act synergistically.8,9 Second, existing diagnostic criteria all required that memory impairment be present to diagnose VaD and this was at odds with clinical experience.5,6,10,11 Finally, with improved clinical recognition of earlier stages of cognitive impairment and increasing emphasis on prevention, the VaD construct was not sensitive to the clinical phenotype of cognitive impairment of a presumed vascular cause that was not severe enough to meet the criteria for dementia. The VCI construct therefore includes a broader spectrum of clinical profiles. These range from individuals with cognitive impairment not dementia, individuals who meet the criteria for VaD (poststroke dementia, MID, etc.) and individuals in whom cognitive impairment shows mixed “primary” neurodegenerative (PND) and vascular features (mixed PND/VaD).12
Paige A. Moorhouse Kenneth Rockwood
The development of the VCI construct represents advan ces in how we understand cognitive impairment that is related to cerebrovascular disease. It recognizes that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease, such as chronic hypoperfusion, which may account for the pattern of cognitive deficits (another old idea that has become modern again). It also affords greater attention to opportunities for primary and secondary prevention.13 The VCI construct also recognizes that more than one cause of dementia might exist in the same patient. Even so, the formulation of the VCI construct is not entirely settled. In consequence, the ongoing debate regarding the precision of the construct14,15 and the ever-changing terminology have posed significant challenges to ongoing research in the area. For example, estimates of incidence and prevalence of VCI rely on varied definitions. Similarly inclusion criteria for research studies vary according to the diagnostic criteria used and hamper meta-analyses and external validity. Incomplete agreement on terminology has also undermined development of standardized language and criteria for vascular lesions in neuropathology and neuroimaging.16
EPIDEMIOLOGY VCI is common. Approximately one third of dementia cases show significant vascular pathology on autopsy,7,17 although this does not indicate the clinical relevance of such pathology. Depending on how cerebrovascular mechanisms are understood, VCI can be considered the most common form of cognitive impairment14 but it is most commonly referred to as the second most common form of cognitive impairment (after Alzheimer’s disease). The novelty and the heterogeneity of the VCI construct (particularly the inclusion of those with VCI-ND) create challenges for descriptive epidemiology, much of which still relies on vascular dementia terminology. In the Canadian Study of Health and Aging, it was estimated that approximately 5% of people over the age of 65 had VCI, with 2.4% having VCI-ND, 0.9% having mixed dementia, and 1.5% having VaD.18 The incidence of vascular dementia ranges from 6 to 12 cases per 1000 over the age of 70 per year.19
SUBTYPES OF VCI As argued elsewhere,1 given the considerable heterogeneity within VCI, subgroup classification is necessary. Proposed subgroup schemata have distinguished subtypes on the basis of neuropathology, risk factors, and treatment response,20 but in practice VCI is a clinical diagnosis, often supported by neuroimaging, therefore subgroups will be described here on the basis of their clinical presentation. Clinical subgroups include VCI-ND, mixed PND/VaD, and VaD. In this classification system, disorders originally included in the VaD construct, such as poststroke dementia, multi-infarct dementia, subcortical dementia, and leukoaraiosis remain in the VaD subtype. This system is not universally agreed upon. 421
Vascular Cognitive Impairment Vascular cognitive impairment (VCI) is a global diagnostic category applied to a heterogeneous group of cognitive disorders that share a presumed vascular cause. Note that it is an umbrella term, which includes several syndromes, and is not simply the vascular counterpart of mild cognitive impairment (MCI). Specifically, VCI includes vascular dementia (including poststroke and multi-infarct dementia), mixed primary neurodegenerative disease and vascular dementia, and cognitive impairment of vascular origin that does not meet dementia criteria (VCI-ND). VCI may be preventable, although the evidence for this is not as complete as it is for the prevention of stroke. Beyond prevention, specific treatment has shown limited efficacy. Updated clinical diagnostic criteria for VCI are needed, and clinical investigators now emphasize harmonized standards to study the clinical, neuropathologic, and neuroimaging manifestations of VCI in daily practice. This chapter builds on a recent review1 to outline the evolution of the VCI construct, presents current thinking regarding clinical diagnosis and the supportive role of neuroimaging, and addresses the challenges that will shape future developments in this area.
HISTORICAL OVERVIEW The conceptual prototype for VCI was “multi-infarct dementia” (MID),2 itself an improvement over “senile dementia due to hardening of the arteries.”3 Like many prototypes, MID was constructed with inefficient tools: neuropsychological testing based on the Alzheimer’s disease paradigm and (initially) no or rudimentary neuroimaging. This construct defined MID as dementia arising as a consequence of multiple strokes and was said to account for 15% of dementias.4 As neuroimaging techniques evolved, the array of vascular pathologies outgrew the MID construct, so the vascular dementia (VaD) construct (of which MID became a subtype) was created to allow more flexibility in the size and distribution of neuroimaging abnormalities (from single strategic infarcts to leukoaraiosis) related to the diagnosis.5,6 Like its forerunner, the VaD construct was soon outgrown due to at least three key developments. First, growing neuropathologic evidence indicated that most dementias have both neurodegenerative (most commonly Alzheimer disease [AD]) and vascular features7 and that these features appear to act synergistically.8,9 Second, existing diagnostic criteria all required that memory impairment be present to diagnose VaD and this was at odds with clinical experience.5,6,10,11 Finally, with improved clinical recognition of earlier stages of cognitive impairment and increasing emphasis on prevention, the VaD construct was not sensitive to the clinical phenotype of cognitive impairment of a presumed vascular cause that was not severe enough to meet the criteria for dementia. The VCI construct therefore includes a broader spectrum of clinical profiles. These range from individuals with cognitive impairment not dementia, individuals who meet the criteria for VaD (poststroke dementia, MID, etc.) and individuals in whom cognitive impairment shows mixed “primary” neurodegenerative (PND) and vascular features (mixed PND/VaD).12
Paige A. Moorhouse Kenneth Rockwood
The development of the VCI construct represents advan ces in how we understand cognitive impairment that is related to cerebrovascular disease. It recognizes that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease, such as chronic hypoperfusion, which may account for the pattern of cognitive deficits (another old idea that has become modern again). It also affords greater attention to opportunities for primary and secondary prevention.13 The VCI construct also recognizes that more than one cause of dementia might exist in the same patient. Even so, the formulation of the VCI construct is not entirely settled. In consequence, the ongoing debate regarding the precision of the construct14,15 and the ever-changing terminology have posed significant challenges to ongoing research in the area. For example, estimates of incidence and prevalence of VCI rely on varied definitions. Similarly inclusion criteria for research studies vary according to the diagnostic criteria used and hamper meta-analyses and external validity. Incomplete agreement on terminology has also undermined development of standardized language and criteria for vascular lesions in neuropathology and neuroimaging.16
EPIDEMIOLOGY VCI is common. Approximately one third of dementia cases show significant vascular pathology on autopsy,7,17 although this does not indicate the clinical relevance of such pathology. Depending on how cerebrovascular mechanisms are understood, VCI can be considered the most common form of cognitive impairment14 but it is most commonly referred to as the second most common form of cognitive impairment (after Alzheimer’s disease). The novelty and the heterogeneity of the VCI construct (particularly the inclusion of those with VCI-ND) create challenges for descriptive epidemiology, much of which still relies on vascular dementia terminology. In the Canadian Study of Health and Aging, it was estimated that approximately 5% of people over the age of 65 had VCI, with 2.4% having VCI-ND, 0.9% having mixed dementia, and 1.5% having VaD.18 The incidence of vascular dementia ranges from 6 to 12 cases per 1000 over the age of 70 per year.19
SUBTYPES OF VCI As argued elsewhere,1 given the considerable heterogeneity within VCI, subgroup classification is necessary. Proposed subgroup schemata have distinguished subtypes on the basis of neuropathology, risk factors, and treatment response,20 but in practice VCI is a clinical diagnosis, often supported by neuroimaging, therefore subgroups will be described here on the basis of their clinical presentation. Clinical subgroups include VCI-ND, mixed PND/VaD, and VaD. In this classification system, disorders originally included in the VaD construct, such as poststroke dementia, multi-infarct dementia, subcortical dementia, and leukoaraiosis remain in the VaD subtype. This system is not universally agreed upon. 421