Vascular cognitive impairment (VCI): Progress towards knowledge and treatment

Abstract

Until recently, the study of cognitive impairment as a manifestation of cerebrovascular disease (CVD) has been hampered by the lack of common standards for assessment. The term vascular cognitive impairment (VCI) encompasses all levels of cognitive decline associated with CVD from mild deficits in one or more cognitive domains to crude dementia syndrome. VCI incorporates the complex interactions among classic vascular risk factors (i.e. arterial hypertension, high cholesterol, and diabetes), CVD subtypes, and Alzheimer’s Disease (AD) pathology. VCI may be the earliest, commonest, and subtlest manifestation of CVD and can be regarded as a highly prevalent and preventable syndrome. However, cognition is not a standardized outcome measure in clinical trials assessing functional ability after stroke. Furthermore, with the exception of anti-hypertensive medications, the impact of either preventive or acute stroke treatments on cognitive outcome is not known. Although clinical, epidemiological, neuroimaging, and experimental data support the VCI concept, there is a lack of integrated knowledge on the role played by the most relevant pathophysiological mechanisms involved in several neurological conditions including stroke and cognitive impairment such as excitotoxicity, apoptosis, mitochondrial DNA damage, oxidative stress, disturbed neurotransmitter release, and inflammation. For this reason, in 2006 the National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) defined a set of data elements to be collected in future studies aimed at defining VCI etiology, clinical manifestations, predictive factors, and treatment. These recommendations represent the first step toward developing diagnostic criteria for VCI based on sound knowledge rather than on hypotheses. The second step will be to integrate all studies using the agreed methodologies. This is likely to accelerate the search for answers.

Prevalence of dementia subtypes in a developing country: a clinicopathological study

“…Even the nature of the cerebrovascular lesions believed to cause cognitive decline varies considerably (13,23). In addition, it is now clear that the amount of brain destruction required to cause dementia is smaller than was previously appreciated (13,25). We used conservative criteria because only cases with large chronic infarcts or lacunar or microinfarcts in strategic areas were diagnosed with VaD.…”

Biomarkers in vascular dementia: A recent update

“…The characteristic pathology such as microvascular angiopathy, CADASIL, hypertensive vasculopathy, cerebral amyloid angiopathy (CAA), and atheroembolic or thrombotic diseases have been identified and well-documented. 1,7,73 Various pathological VaD biomarkers are illustrated in Table 3. Theses biomarkers can be divided into six major categories: (1) biomarkers of CADASIL; (2) biomarkers of microvessel angiopathy; (3) biomarkers of hypertensive vasculopathy; (4) biomarkers of cerebral amyloid angiopathy; (5) biomarkers of atherosclerosis or thrombotic disease; and (6) CB formation due to mitochondrial degeneration and eventually apoptosis of the most vulnerable cells in the hippocampal dentate gyrus and CA-3 regions due to cerebrovascular insufficiency in VaD.…”

“…Novel potential biomarkers of VaD such as asymmetrical dimethylarginine, which is a biomarker of endothelial dysfunction, adhesion molecule P-selectin may contribute to vascular processes and thereby dementia need larger studies and validation. 7 Currently CSF isoprostane, a biomarker of oxidative stress, Ab oligomer, a synuclein, TDP-43, CSF DJ-1, TDP-43 are being investigated in AD. As dementia is defined as mixed etiology, there is a dire need to consider all these biomarkers along with newer biomarkers of vascular injury in determining causal relationship to VaD.…”

“…Dysfunction of autonomic regulation of cerebral blood flow is also associated with VaD where imaging biomarkers may provide diagnostic utility. 7 There has not been any consensus on criteria, definitions, or analysis of VaD in neuropathological assessment. Although numerous gross and microscopic changes have been identified as diagnostic of VaD, there is a need of multidisciplinary team performing large multicenter clinicopathological studies and harmonize the diagnostic approach and validate the biomarkers under investigation; e.g.…”

“…The original term multi-infarct dementia is now replaced by a newly updated term, vascular cognitive impairment (VCI), which refers to any cognitive impairment caused by or associated with vascular risk factors and ranges from mild cognitive impairment to overt dementia. 7 VaD may be caused by hemorrhagic, ischemic, and hypoxic injury to the brain. It is a group of heterogeneous disorders in which the presence of ischemia/infarction may cause cognitive decline however, the degree of such impairment is directly proportional to the extent of neuronal damage and location of the lesion.…”