Cardiovascular Risk in Adult FASD its Impact on Prefrontal Cortical Functioning

成人FASD心血管风险对前额皮质功能的影响

JULIE KABLE (2018-09-26 to 2020-08-31) $370,500

Project ID: R21AA027345 (NIAAA)

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Abstract

Fetal Alcohol Spectrum Disorders (FASDs) is a term used to describe a range of effects seen in individuals who have a history of prenatal alcohol exposure (PAE). Since the original recognition of Fetal Alcohol Syndrome, the most extreme variant of these effects, over 40 years of research has been amassed documenting the physical and neurobehavioral impact of PAE. Surprisingly though, there exist only a handful of studies that have examined the long-term impact of PAE in adulthood despite recent interests in exploring the developmental origins of health and disease among the scientific community. We are proposing to assess the cardiovascular risk of adults who are between 30-40 years of age who were recruited while in utero and followed over time as part of a prospective cohort of alcohol-exposed individuals and a control group with comparable socio-economic characteristics who did not have PAE. The individuals from the cohort were last seen in their 20's and are actively being recruited for a study whose aims are to characterize the characteristics of FASD in adulthood and to assess their health status in adulthood, using predominantly self-report and medical record abstraction. As part of the assessment proposed for this study, we will obtain traditional measures of cardiovascular risk, including blood pressure, triglycerides (total, high and low density lipids), cholesterol, and fasting glucose levels, and a measure of microvascular peripheral functioning, using peripheral arterial tonometry (PAT). We will further assess the impact of microvascular peripheral function on prefrontal cortical (PFC) activation using functional near-infrared spectroscopy (fNIRS) to assess the impact the level of vascular occlusion has on oxygen perfusion in this area of the brain that is heavily involved in inhibitory control and higher level reasoning and judgement. FNIRS assesses levels of oxygenated (HBO) and deoxygenated (HBR) hemoglobin by emitting infrared light through human tissue, which is nearly transparent to light in this range. This method has been validated by documenting changes in blood oxygenation levels relative those obtained in fMRI and PET studies and has the advantage of being lower cost and providing estimates of both HBO and HBR. Hemodynamic changes in the brain have been used previously to differentiate clinical groups, including children with a history of PAE, and to be related to parent-reported measures of behavioral functioning. In this study, we will relate indices of PFC brain hemodynamic changes to neurobehavioral functioning, specifically executive functioning skills, and assess how these relationships are influenced by peripheral microvascular functioning. Previous research has established that PAE can disrupt vascular development in animal models and this proposal will allow us to evaluate alterations in cardiovascular functioning and the impact of this on the perfusion of oxygen to the PFC and to determine if this mechanisms underlies the neurobehavioral deficits seen in individuals with FASDs. .

胎儿酒精谱系障碍（FASDs）是一个术语，用于描述有产前酒精暴露史（PAE）的个体所见的一系列影响。自最初识别胎儿酒精综合症（这些效应的最极端变体）以来，已经积累了40多年的研究成果，记录了PAE的物理和神经行为影响。令人惊讶的是，尽管最近有兴趣探索科学界的健康和疾病的发展起源，但只有少数研究检验了PAE在成年期的长期影响。我们建议评估30-40岁之间在子宫内被招募的成年人的心血管风险，并作为前瞻性酒精暴露人群和具有可比社会经济特征的对照组的一部分进行随访。谁没有PAE。来自该队列的个体最后一次出现在他们的20多岁，并且正在积极地被招募进行一项研究，其目的是描述成年期FASD的特征并评估他们在成年期的健康状况，主要使用自我报告和医疗记录抽象。作为本研究提出的评估的一部分，我们将获得心血管风险的传统测量方法，包括血压，甘油三酯（总胆固醇，高密度和低密度脂质），胆固醇和空腹血糖水平，以及微血管外周功能的测量，使用外周动脉张力计（PAT）。我们将使用功能性近红外光谱（fNIRS）进一步评估微血管外周功能对前额皮质（PFC）激活的影响，以评估血管闭塞水平对大量参与的大脑中的氧灌注的影响。抑制控制和更高层次的推理和判断。 FNIRS通过人体组织发射红外光来评估氧合（HBO）和脱氧（HBR）血红蛋白的水平，人体组织对此范围内的光几乎是透明的。该方法已经通过记录相对于fMRI和PET研究中获得的血氧水平变化进行了验证，并且具有成本更低和提供HBO和HBR估计的优点。先前已经使用大脑中的血液动力学变化来区分临床组，包括具有PAE病史的儿童，并且与父母报告的行为功能测量相关。在本研究中，我们将PFC脑血流动力学变化的指标与神经行为功能，特别是执行功能技能相关联，并评估这些关系如何受外周微血管功能的影响。以前的研究已经确定PAE可以破坏动物模型中的血管发育，这个提议将允许我们评估心血管功能的改变及其对氧气灌注到PFC的影响，并确定这种机制是否是神经行为缺陷的基础。有FASDs的人。。