Spectrum of cognitive decline, caused by or associated with vascular pathology, including mild impairment in cognition: VCI; and dementia: VaD.
2nd M/C cause of cognitive impairment and dementia in the elderly (after Alzheimer’s disease (AD))
History:
The concept of VCI, was proposed by Sachdev in 1999 to describe the cognitive deficit of vascular origin severe enough to meet the criteria for a diagnosable disorder. It was initially ascribed to cognitive impairment of vascular origin not significant enough to impair activities of daily living (ADL), i.e., cognitive impairment that does not meet the requirements for dementia. The term now however refers to a broad spectrum of cognitive and behavioural changes associated with cerebral vascular pathology, characterized by attention and executive impairment ranging from early cognitive decline to dementia. VCI therefore encompasses all the cognitive disorders associated with cerebrovascular disease.
Relationship between VCI and vascular dementia: Vascular cognitive impairment (VCI) refers to any degree of cognitive impairment that is associated with any severity of vascular pathology. As such, VCI can refer to subjective cognitive impairment, mild cognitive impairment (MCI) and dementia. In addition, VCI can refer to a clinical syndrome that is entirely caused by cerebrovascular pathology or a syndrome whereby any degree of cerebrovascular pathology has, to some extent, contributed to cognitive impairment. Vascular dementia refers to a subgroup of patients who have dementia that is largely attributable to cerebrovascular pathology | van der Flier, W., Skoog, I., Schneider, J. et al. Vascular cognitive impairment. Nat Rev Dis Primers 4, 18003 (2018). https://doi.org/10.1038/nrdp.2018.3
Aetiology
Risk factors:
The risk factors for dementia overlap with those for stroke supporting the concept of a shared susceptibility, as also suggested by the epidemiological relationship between these 2 disorders
Increasing age (biggest risk factor)
Female sex
Genetic factors:
CADASIL
Apolipoprotein E4 (strong risk factor especially in women)
Risk Factors for Dementia
Risk factors for vascular dementia, post-stroke dementia, dementia of unspecified etiology (unspecified dementia), and Alzheimer’s dementia. | Dichgans M, Leys D. Vascular Cognitive Impairment. Circ Res 2017;120:573–91. | Pendlebury S, Rothwell P, for the Oxford Vascular Study. Incidence and prevalence of dementia associated with TIA and stroke: rates and risk factors in a population-based cohort. Lancet Neurol 2019;18:248–58.
Pathophysiology
Cerebrovascular cells are closely related to brain cells, and their interaction plays a critical role in brain development, maintenance, and function, both in health and disease
Mechanisms of VCI: Several biological mechanisms might link vascular disease to cognitive impairment, although the order in which these processes occur is difficult to identify. The underlying mechanisms of vascular cognitive impairment (VCI) and the effects of these mechanisms on brain processes is variable between patients. Risk factors, some types of cerebral vessel diseases and tissue injuries interact with these mechanisms and brain processes, each leading by itself or in combination to cognitive impairment and dementia, and the other clinical signs and symptoms of VCI. CAA. cerebral amyloid angiopathy; WMHs, white matter hyperintensities. | van der Flier, W., Skoog, I., Schneider, J. et al. Vascular cognitive impairment. Nat Rev Dis Primers 4, 18003 (2018). https://doi.org/10.1038/nrdp.2018.3
Leukoaraiosis: thinning of the white matter
the earliest changes are usually those of small vessel disease producing white matter changes.
Neuropathology of VCI: Small-vessel disease pathologies: (A) chronic microscopic infarct in the anterior caudate nucleus on hematoxylin & eosin stain; (B) microbleed surrounding damaged cortical blood vessel in the temporal lobe on hematoxylin & eosin stain; (C) arteriolosclerosis in the basal ganglia on hematoxylin & eosin; (D) enlarged perivascular spaces on hematoxylin & eosin stain; (E) white matter pallor in the posterior watershed region on Luxol fast blue and hematoxylin stain; and (F) amyloid angiopathy and Alzheimer’s disease pathology in the midfrontal cortex (immunohistochemistry with the anti-β-amyloid antibody 4G8). | Iadecola, C., Duering, M., Hachinski, V., Joutel, A., Pendlebury, S. T., Schneider, J. A., & Dichgans, M. (2019). Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel. Journal of the American College of Cardiology, 73(25), 3326–3344. https://doi.org/10.1016/j.jacc.2019.04.034
Sites associated with dementia include basal forebrain, medial temporal, thalamic or parieto-occipital infarcts.
Macroscopic and microscopic vascular pathology at autopsy: a) Macroscopic aspect of a lacunar infarct in the thalamus (arrow). b) Small haemorrhage in the subcortical white matter of the superior temporal gyrus (arrow), which could appear as a microbleed when detected using neuroimaging. c) Atherosclerosis at the circle of Willis, including atherosclerotic plaques in the vertebral artery (white arrows) and the basilar artery (black arrows). In addition, atherosclerosis in what seems to be theposterior cerebral and posterior communicating arteries can be observed. d) Microscopic aspect of microinfarct. e) Microhaemorrhage. f) Arteriolosclerosis. | van der Flier, W., Skoog, I., Schneider, J. et al. Vascular cognitive impairment. Nat Rev Dis Primers 4, 18003 (2018). https://doi.org/10.1038/nrdp.2018.3
Classificaiton
Vascular Impairment of Cognition Classification Consensus Study (VICCCS) classification:
4 major subtypes
Post-stroke dementia (PSD): Dementia manifesting within 6 months after a stroke
Subcortical ischemic vascular dementia (SIVaD)
Multi-infarct (cortical) dementia
Mixed dementia
Classification of VCI:
Diagnostic classification for major vascular cognitive impairment (VCI) (major VCI = vascular dementia [VaD]). The 6-month temporal basis for cognitive decline after stroke (dashed box) differentiates post-stroke dementia (PSD) from other forms of VaD. | *Patients who also have evidence for comorbid pathology representing an established nonvascular cause of dementia such as Alzheimer’s disease (AD) or dementia with Lewy bodies (DLB) are classified as mixed dementia. Mild VCI refers to impairment in at least 1 cognitive domain and mild to no impairment in instrumental activities of daily living or activities of daily living (independent of the motor/sensory sequelae of the vascular event) | Skrobot OA, Black SE, Chen C, et al. Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement 2018;14: 280–92.
Clinical features
VCI is not a single disorder, rather it is a spectrum of conditions with heterogeneous clinical presentations, aetiologies and treatment. VCI is characterized by deficit in executive functioning (planning, task flexibility, problem solving, etc.)
Multi infarct dementia:
Characterised by recurrent stroke, stepwise course, focal neurological symptoms and signs, and multiple cerebral infarcts on brain imaging.
Strategic infarct dementia:
Characterized by an abrupt onset of memory impairment or behavioural change in association with a single, strategically placed infarct.
Subcortical vascular dementia:
Subcortical vascular dementia encompasses the earlier entities, Binswanger’s disease and lacunar state and is characterised by a dysexecutive syndrome with mild memory loss, early gait disorder, Parkinsonian features, behavioral, and urinary symptoms.
Diagnosis
For a diagnosis of VaD or mild VCI, the new VICCCS guideline generally requires magnetic resonance imaging (MRI) and evidence of vascular lesions that qualify for one of the major diagnostic subtypes
Structural MRI:
MRI manifestations of cerebrovascular disease: a) Large vessel infarct detected using fluidattenuated inversion recovery (FLAIR) sequences. b) Microinfarct detected using T1weighted MRI. c) Macroscopic haemorrhage detected using CT. d) Multiple microbleeds indicative of cerebral amyloid angiopathy detected using susceptibility-weighted imaging (arrows point to three representative microbleeds). e) Extensive white matter hyperintensities (WMHs) detected using FLAIR sequences (arrows point to representative WMHs). f) Superficial siderosis detected using susceptibility-weighted imaging (arrows point to representative areas of superficial siderosis). | Part b courtesy of Susanne van Veluw, Massachusetts General Hospital, USA. | van der Flier, W., Skoog, I., Schneider, J. et al. Vascular cognitive impairment. Nat Rev Dis Primers 4, 18003 (2018). https://doi.org/10.1038/nrdp.2018.3
Differential diagnosis:
Comparison of vascular dementia and Alzheimer disease | Lee, A. Y. (2011). Vascular dementia. Chonnam Medical Journal, 47(2), 66–71. https://doi.org/10.4068/cmj.2011.47.2.66
Management
The main management strategy for VCI is the symptomatic treatment of VaD, management of risk factors as well non-pharmacological approaches aimed at preventing progression to VaD.
Summary:
The risk factors for vascular cognitive impairment (VCI) which include demographic factors, lifestyle factors and the presence of some chronic disorders | Vascular cognitive impairment. Nat Rev Dis Primers 4, 18004 (2018). https://doi.org/10.1038/nrdp.2018.4
