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Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition.

ABSTRACT: Recent clinical data indicates that hemodynamic changes caused by cardiovascular diseases such as atherosclerosis, heart failure, and hypertension affect cognition. Yet, the underlying mechanisms of the resulting vascular cognitive impairment (VCI) are poorly understood. One reason for the lack of mechanistic insights in VCI is that research in dementia primarily focused on Alzheimer's disease models. To fill in this gap, we critically reviewed the published data and various models of VCI. Typical findings in VCI include reduced cerebral perfusion, blood-brain barrier alterations, white matter lesions, and cognitive deficits, which have also been reported in different cardiovascular mouse models. However, the tests performed are incomplete and differ between models, hampering a direct comparison between models and studies. Nevertheless, from the currently available data we conclude that a few existing surgical animal models show the key features of vascular cognitive decline, with the bilateral common carotid artery stenosis hypoperfusion mouse model as the most promising model. The transverse aortic constriction and myocardial infarction models may be good alternatives, but these models are as yet less characterized regarding the possible cerebral changes. Mixed models could be used to study the combined effects of different cardiovascular diseases on the deterioration of cognition during aging.

SUBMITTER: Bink DI

PROVIDER: S-EPMC3824184 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition.

Bink Diewertje I DI Ritz Katja K Aronica Eleonora E van der Weerd Louise L Daemen Mat J A P MJ

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20130821 11

Recent clinical data indicates that hemodynamic changes caused by cardiovascular diseases such as atherosclerosis, heart failure, and hypertension affect cognition. Yet, the underlying mechanisms of the resulting vascular cognitive impairment (VCI) are poorly understood. One reason for the lack of mechanistic insights in VCI is that research in dementia primarily focused on Alzheimer's disease models. To fill in this gap, we critically reviewed the published data and various models of VCI. Typic ...[more]

PMID: 23963364

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Project description:BackgroundObservational studies suggest that early menopause is associated with increased risk of death and cardiovascular disease (CVD); however, the results of these studies have been inconsistently. We aimed to assess the association of menopause with death and CVD and whether this association was modified by cardiovascular risk factors.MethodsThe study population was women age 35-64 years living in two communities of Beijing who were enrolled in the Chinese Multi-provincial Cohort Study in 1992. Participants were followed until first cardiovascular event, death, or the end of follow-up (2018). Self-reported age at menopause was recorded. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of death and CVD after adjusting for baseline covariates of age, family history of CVD, and white blood cell count, as well as time-varying covariates of menopause, use of oral estrogen, and conventional risk factors. Additionally, we assessed the combined effect of age at menopause and risk factors on the primary endpoint.ResultsOf 2104 eligible women, 124 died and 196 had a first CVD event (33 fatal CVD and 163 non-fatal CVD). Compared with women who experienced menopause at age 50-51 years, the risk of death was higher in women with menopause at age 45-49 years (HR 1.99, 95% CI 1.24-3.21; P = 0.005), and the risk of ischemic stroke was higher in women with menopause at age < 45 years (HR 2.16, 95% CI 1.04-4.51; P = 0.04) and at age 45-49 years (HR 2.05, 95% CI 1.15-3.63; P = 0.01). Women who had menopause before age 50 years and at least one elevated risk factor at baseline had a higher risk of death (HR 11.10, 95% CI 1.51-81.41; P = 0.02), CVD (HR 3.98, 95% CI 1.58-10.01; P = 0.003), ischemic CVD (HR 4.53, 95% CI 1.63-12.62; P = 0.004), coronary heart disease (HR 8.63, 95% CI 1.15-64.50; P = 0.04), and stroke (HR 2.92, 95% CI 1.03-8.29; P = 0.04) than those with menopause at age 50-51 years and optimal levels of all risk factors.ConclusionsEarlier menopause may predict death and ischemic stroke. Furthermore, there is a combined effect of earlier menopause and elevated risk factors on death and CVD.

Project description:PurposeTo investigate the association of characteristics of type 2 diabetes mellitus (duration and biochemical severity of diabetes) to brain structure measured on magnetic resonance (MR) images, specifically testing whether more severity in metrics of diabetes is inversely correlated with brain volumes and positively correlated with ischemic lesion volumes.Materials and methodsThis study protocol was approved by the institutional review board of each center and participants provided written informed consent. Baseline severity of diabetes was evaluated by testing fasting plasma glucose levels, hemoglobin A1c levels, and duration of diabetes. MR imaging was performed with fluid-attenuated inversion recovery, proton-density, T2-weighted, and T1-weighted sequences, which were postprocessed with an automated computer algorithm that classified brain tissue as gray or white matter and as normal or ischemic. Separate linear regression models adjusted for potential confounding factors were used to investigate the relationship of the diabetes measures to MR imaging outcomes in 614 participants (mean age, 62 years; mean duration of type 2 diabetes mellitus, 9.9 years).ResultsThe mean volumes of total gray matter (463.9 cm(3)) and total white matter (463.6 cm(3)) were similar. The mean volume of abnormal tissue was 2.5 cm(3), mostly in the white matter (81% white matter, 5% gray matter, 14% deep gray and white matter). Longer duration of diabetes and higher fasting plasma glucose level were associated with lower normal (β = -0.431 and -0.053, respectively; P < .01) and total gray matter volumes (β = -0.428 and -0.053, respectively; P < .01). Fasting plasma glucose was also inversely correlated with ischemic lesion volume (β = -0.006; P < .04). Hemoglobin A1c level was not associated with any MR imaging measure.ConclusionLonger duration of diabetes is associated with brain volume loss, particularly in the gray matter, possibly reflecting direct neurologic insult; biochemical measures of glycemia were less consistently related to MR imaging changes. Contrary to common clinical belief, in this sample of patients with type 2 diabetes mellitus, there was no association of diabetes characteristics with small vessel ischemic disease in the brain.

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Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition.

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Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition.

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