Cognitive Patterns in Relation to Biomarkers of Cerebrovascular Disease and Vascular Risk Factors

Abstract

Background: Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. Methods: TheBarcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Results: Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. Conclusion: Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages.

Pharmacologically-Induced Neurovascular Uncoupling is Associated with Cognitive Impairment in Mice

“…First, a wide range of pathophysiologic conditions were shown to adversely affect the synthesis of vasodilator NO, EETs, and prostaglandins, promoting neurovascular uncoupling. For example, several cardiovascular risk factors, including hypertension, dyslipidaemia, smoking, and obesity, which are important risk factors for cognitive decline in elderly patients, 36,40 were shown to decrease the bioavailability of NO in the microcirculation by promoting oxidative stress, uncoupling endothelial NO synthase, and by upregulating asymmetric dimethylarginine, an endogenous inhibitor of NO synthase. Aging itself was shown to cause neurovascular uncoupling, at least in part, by impairing NO mediation of the response.…”

N-Terminal Prosomatostatin and Risk of Vascular Dementia

“…The identification of novel biomarkers may also permit an early detection of individuals who are at a higher risk of developing dementia. Since a variety of cardiovascular risk factors including hypertension, smoking, dyslipidaemia, and prevalent cardiovascular disease (CVD) all have been associated with development of dementia [7,8,9,] in recent years, there has been growing interest in linking cardiovascular biomarkers to dementia risk [10]. …”

Vascular Cognitive Disorders and Depression After First-Ever Stroke: The Fogarty-Mexico Stroke Cohort

“…The prevalence of vascular dementia (VaD) in stroke survivors is about 30% and incident dementia doubles after stroke [4]. Very few studies in developing countries have addressed the continuum of Vascular Cognitive Disorders ranging from vascular cognitive impairment (VCI) to VaD [5,] despite higher rates of mortality and functional impairment in VaD patients [4,6]. Post-stroke VCI is far more common than VaD and often goes undetected in routine neurological assessments [7], particularly when specific cognitive areas are affected, such as executive dysfunction causing impairment of activities of daily living and delayed stroke rehabilitation.…”