Preeclampsia and the Brain: Small vessel disease and cognitive function in early midlife

脑小血管疾病(CSVD)易导致血管认知障碍和痴呆，包括 阿尔茨海默氏症。子痫前期(PE)，一种妊娠特有的疾病，伴有急性高血压和胎盘 SVD，正在成为晚年痴呆的性别特有的风险因素。PE是如何牵涉到糖尿病的病因学的 痴呆症尚不为人所知。患有PE的女性在其他血管床上也有SVD，包括大脑 随着年龄的增长，怀孕和病情恶化，这表明这个过程会随着时间的推移而演变。然而，关于奇异值分解的研究 在中年是稀少的。中年是评估这种风险的理想时机，因为认知上的差异已经存在 可以检测到，但仍有时间减缓痴呆症的进展。中年大脑SVD(CSVD)可能持续 了解PE是如何导致认知障碍的关键。 被称为母体血管灌注不良(MVM)的胎盘SVD预示着更糟糕的短期妊娠 结果。我们发现，MVM和PE联合预测母体心脏血管健康长期较差， 舌下床和大脑床。在我们的初步研究中(n=24)，MVM和PE联合预测较低 脑血管反应性(CVR，cSVD的早期阶段)，特别是在额顶区；反过来，较低的CVR 这些区域与体育相关的认知不良有关，而且似乎可以解释。 重要的是，这些 研究结果与高血压无关，表明PE对血管有直接和持久的影响 。Pe和 MVM可能是未来脑血管表型的早期指标，表现为中年时CVR较低，以及 或许可以解释体育是如何影响认知的。我们建议对有和没有PE史的中年女性进行研究：1) 描述PE相关认知能力低下的神经基础，2)评估胎盘SVD (MVM)预测cSVD和认知，以及3)探讨SVD的舌下和SVD的循环标志物 是cSVD和认知的标记物。 我们提出了一项神经认知研究，以捕捉cSVD的早期阶段和不同种族的认知状态 一群人 四百五十 来自我们正在进行的WINDOWS研究的女性(1：1 PE和非PE)，平均年龄=45岁，15岁后 怀孕，30%为黑人，怀孕10年后有PE、MVM和舌下SVD的现有数据。我们会 使用我们先进的多模式神经成像协议来量化cSVD(包括CVR、血流、 连通性)，测量认知的标准化验证方案，以及SVD的非侵入性标记 (语下奇异值分解，以及 循环生物标记物概况) 。我们的项目处于独特的位置，可以识别以前的 通过胎盘病理可以在分娩时发现的神秘高危人群，他们可能从风险中受益- 对痴呆症进行分层，以减轻或延缓疾病进展。

Cerebral small vessel disease (cSVD) predisposes to vascular cognitive impairment and dementia, including Alzheimer’s Disease. Preeclampsia (PE), a pregnancy-specific disorder with acute hypertension and placental SVD, is emerging as a sex-specific risk factor for dementia later in life. How PE is implicated in the etiology of dementia is not known. Women with PE have SVD also in other vascular beds, including the brain, after pregnancy and worsening with older age, suggesting this process evolves over time. However, studies on SVD in midlife are sparse. Midlife is an ideal time to assess this risk as PE-differences in cognition are already detectable, and yet there is time to mitigate progression to dementia. Cerebral SVD (cSVD) in midlife may hold the key to understand how PE is implicated in cognitive impairment. Placental SVD, known as maternal vascular malperfusion (MVM) predicts worse short-term pregnancy outcomes. We find MVM and PE combined predict long-term worse maternal vascular health in cardiac, sublingual, and cerebral beds. In our pilot study (n=24) MVM and PE combined predicted lower cerebrovascular reactivity (CVR, an early stage of cSVD), especially in fronto-parietal areas; in turn, lower CVR in these regions was associated with, and appeared to explain, PE-related worse cognition. Importantly, these findings were independent of hypertension, suggesting PE has direct and lasting vascular effects . PE and MVM may be early indicators of a future cerebrovascular phenotype, manifesting in midlife as lower CVR, and may explain how PE affects cognition. We propose to study midlife women with and without prior PE to: 1) Characterize the neural basis of PE-related poorer cognitive performance, 2) Assess whether placental SVD (MVM) predicts cSVD and cognition, and 3) Explore whether sublingual SVD and circulating markers of SVD are markers of cSVD and cognition. We propose a neurocognitive study to capture early stages of cSVD and cognitive status in a racially diverse cohort of 450 women (1:1 PE and non PE) from our ongoing WINDOWS study, mean age=45, 15 years post- pregnancy, 30% black, with existing data on PE, MVM, and sublingual SVD 10 years after pregnancy. We will use our advanced multimodal neuroimaging protocols to quantify cSVD (including CVR, blood flow, connectivity), standardized validated protocols to measure cognition, and non-invasive markers of SVD (sublingual SVD, and circulating biomarker profiles) . Our project is uniquely positioned to identify a previously occult high-risk group that can be identified at delivery by placental pathology, and who may benefit from risk- stratification for dementia, to mitigate or delay disease progression.