Structural brain changes and cognition in relation to markers of vascular dysfunction

Miralbell, Júlia; Soriano, Joaquím; Spulber, Gabriela; López‐Cancio, Elena; Arenillas, Juan F.; Bargalló, Núria; Galán, Amparo; Barrios, Maite; Cáceres, Cynthia; Alzamora, María Teresa; Pera, Guillem; Kivipelto, Miia; Wahlund, Lars‐Olof; Dávalos, Antoni; Mataró, María

doi:10.1016/j.neurobiolaging.2011.09.020

Cited by 50 publications

(47 citation statements)

References 44 publications

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“…In this study, PAI-1 did not predict cognitive performance in any cognitive domain. This contrasts with our previous findings in a diffusion tensor imaging study in which increasing PAI-1 levels were related to disruption of white matter tracts and lower processing speed [14]. Elevated levels of PAI-1 have also been found in nonamnestic mild cognitive impairment and VaD patients [15,16].…”

Section: Discussioncontrasting

confidence: 97%

“…In that context, the observed impairment in verbal fluency could be partly explained by vascular-related disruption of fronto-subcortical circuits. This is consistent with previous diffusion tensor imaging studies showing an association between increasing levels of CRP and white matter integrity loss in cortico-subcortical pathways and association fibers [14]. …”

Section: Discussionsupporting

confidence: 93%

“…Systemic inflammatory markers, such as C-reactive protein (CRP), have been strongly linked to CVD, cognitive decline, vascular dementia (VaD) and Alzheimer disease (AD) [13,14]. Markers of endothelial dysfunction and vascular thrombosis are elevated in patients with nonamnestic, mild cognitive impairment [15,16], VaD and AD [17], and in magnetic resonance imaging studies are shown to be linked to small vessel disease [18,19].…”

Section: Introductionmentioning

confidence: 99%

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

Miralbell

López‐Cancio²,

López-Olóriz³

et al. 2013

Cerebrovasc Dis

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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.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Miralbell

López‐Cancio²,

López-Olóriz³

et al. 2013

Cerebrovasc Dis

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“…CRP or IL6 was associated with reduced total brain volume (TBV)(35), total gray matter volume (TGMV)(36-38), total white matter volume (TWMV)(37), and hippocampal volume(36, 37, 39). However, CRP and IL6 were not associated with brain volumes in other studies (32, 33, 40-42). Only two studies examined whether inflammatory biomarkers were associated with cortical thickness (CT) and they found inconsistent results(37, 43).…”

Section: Introductioncontrasting

confidence: 53%

Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population

Vorburger

Scarmeas

et al. 2017

Brain, Behavior, and Immunity

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Objective The aim of this investigation was to determine whether circulating inflammatory biomarkers c-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to structural brain measures assessed by magnetic resonance imaging (MRI). Methods High-resolution structural MRI was collected on 680 non-demented elderly (mean age 80.1 years) participants of a community-based, multiethnic cohort. Approximately three quarters of these participants also had peripheral inflammatory biomarkers (CRP, IL6, and ACT) measured using ELISA. Structural measures including brain volumes and cortical thickness (with both global and regional measures) were derived from MRI scans, and repeated MRI measures were obtained after 4.5 years. Mean fractional anisotropy was used as the indicator of white matter integrity assessed with diffusion tensor imaging. We examined the association of inflammatory biomarkers with brain volume, cortical thickness, and white matter integrity using regression models adjusted for age, gender, ethnicity, education, APOE genotype, intracranial volume. Results A doubling in CRP (b= -2.48, p=0.002) was associated with a smaller total gray matter volume, equivalent to approximately 1.5 years of aging. A doubling in IL6 was associated with smaller total brain volume (b= -14.96, p<0.0001), equivalent to approximately 9 years of aging. Higher IL6 was also associated with smaller gray matter (b=-6.52, p=0.002) and white matter volumes (b=-7.47, p=0.004). The volumes of most cortical regions including frontal, occipital, parietal, temporal, as well as subcortical regions including pallidum and thalamus were associated with IL6. In a model additionally adjusted for depression, vascular factors, BMI, and smoking status, the association between IL6 and brain volumes remained, and a doubling in ACT was marginally associated with 0.054 (p=0.004) millimeter thinner mean cortical thickness, equivalent to that of approximately 2.7 years of aging. None of the biomarkers was associated with mean fractional anisotropy or longitudinal change of brain volumes and thickness. Conclusions Among older adults, increased circulating inflammatory biomarkers were associated with smaller brain volume and cortical thickness but not the white matter tract integrity. Our preliminary findings suggest that peripheral inflammatory processes may be involved in the brain atrophy in the elderly.

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“…The control group comprised 17 stroke-free participants from the Barcelona AsIA Neuropsychology study [López-Cancio et al, 2011; Miralbell et al, 2012]. They were screened for absence of cognitive impairment and psychiatric disorder on history and examination, with the same exclusion criteria as the stroke patients.…”

Section: Methodsmentioning

confidence: 99%

Impairment of functional integration of the default mode network correlates with cognitive outcome at three months after stroke

Dacosta-Aguayo

Graña

Iturria-Medina

et al. 2014

Human Brain Mapping

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Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48–72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57–69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P = 0.014; threshold = 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t = 2.01); left parahippocampal gyrus and right superior frontal gyrus (t = 2.11); left parahippocampal gyrus and lSFG (t = 2.39); right parietal and lSFG (t = 2.29). Finally, mean path length obtained from graph-computation analysis showed positive correlations with semantic fluency test (rs = 0.454; P = 0.023), phonetic fluency test (rs = 0.523; P = 0.007) and the mini mental state examination (rs = 0.528; P = 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity. Hum Brain Mapp 36:577–590, 2015. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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Structural brain changes and cognition in relation to markers of vascular dysfunction

Cited by 50 publications

References 44 publications

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

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

Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population

Impairment of functional integration of the default mode network correlates with cognitive outcome at three months after stroke

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