Primary Hyperparathyroidism: Neurocognitive Features

原发性甲状旁腺功能亢进症：神经认知特征

• 批准号: 8967918
• 负责人: MARCELLA Donovan WALKER
• 金额: $ 24万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-09 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967918
• 关键词: Accounting; Address; Affect; Aorta; Area; Blood; Blood Vessels; Brain; Brain region; Calcium; Cerebral hemisphere; Cerebrum; Cognition; Cognitive; Data; Diagnosis; Disease; Disease Management; Disease of parathyroid glands; Educational workshop; Elderly; Endocrine System Diseases; Endocrinology; Epidemiologic Studies; Epidemiology; Etiology; Fibrosis; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Guidelines; Homeostasis; Hormones; Hypercalcemia; Hyperparathyroidism; Image; Impaired cognition; Incidental Discoveries; International; Investigation; Kidney Diseases; Knowledge; Lead; Magnetic Resonance; Maps; Measures; Medial; Memory; Nephrolithiasis; Neurobehavioral Manifestations; Neurocognitive; Neuropsychological Tests; Operative Surgical Procedures; Osteitis; Osteitis Fibrosa Cystica; Parathyroid gland; Parathyroidectomy; Patients; Perfusion; Process; Quality of life; Reporting; Research; Research Project Grants; Risk Factors; Sample Size; Secondary Hyperparathyroidism; Serum; Site; Symptoms; Thick; TimeLine; United States; Vascular Dementia; Vasomotor; Vitamin D Deficiency; Work; cognitive change; cognitive function; design; evidence based guidelines; hemodynamics; improved; innovation; interdisciplinary approach; neuroimaging; neuromuscular; neuropsychological; novel; novel strategies; psychologic; public health relevance; relating to nervous system; symposium; tool

 DESCRIPTION (provided by applicant): Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by over-active parathyroid gland(s) and elevated blood calcium levels. Although 80% of PHPT patients are said to be "asymptomatic" (i.e. lacking the classical manifestations of nephrolithiasis and osteitis fibrosa cystica), this term is a misnomer because most patients report neuropsychological symptoms, including reduced memory and concentration. Although both hypercalcemia and elevated parathyroid hormone (PTH) could have cognitive effects, the mechanism of cognitive dysfunction in PHPT has never been delineated. Most studies do indicate neuropsychological sequelae of PHPT but reversibility after parathyroidectomy (PTX) has been inconsistent across investigations. These inconsistencies may be related to small sample sizes in some studies and variability in the aspects of cognition examined. Because of such limitations, patients with cognitive symptoms are still deemed "asymptomatic" and cognitive dysfunction is not currently an indication for PTX. This remains the biggest unresolved issue in the management of asymptomatic PHPT. Recently, we made progress in this challenging area by showing with validated tools that specific cognitive dysfunction is present in PHPT and improves after surgical cure. A potential vascular mechanism is suggested by our work demonstrating increased aortic and carotid vascular stiffness in PHPT in association with extent of PTH elevation. Our new preliminary data supports the presence of similar PTH-dependent changes in the intracerebral vasculature that may underlie cognitive impairment in PHPT. There is support for this concept from work showing that cerebral hemodynamic dysfunction is associated with cognitive impairment in vascular dementia and carotid disease. Moreover, a recent epidemiological study found elevated PTH to be a risk factor for cognitive decline in older adults. The proposed studies are intended to determine if the above PTH-dependent vascular mechanism is responsible for cognitive dysfunction in PHPT, whether the process is attributable to PTH and reversible with cure of PHPT, and which brain regions are affected. First, we will use transcranial Doppler to confirm that intra- cerebral vasomotor reactivity (VMR) is reduced in PHPT, and associated with elevated PTH (but not calcium) and cognitive changes. Second, we will determine if impaired VMR is reversible with PTX. Finally, we will identify the sites in the brain affected by PHPT using functional magnetic resonance imaging. The data from these studies will address a research goal of the 4th International Conference on Asymptomatic PHPT (2013), which highlighted the need for data regarding the cognitive effects of PHPT. Ultimately this information may lead to alteration of surgical guidelines for PHPT patients. Further, if our hypothesis regarding PTH-dependent changes in cerebral vascular function and cognition is confirmed, these data would have implications for a much broader and larger group of patients with PTH excess, including those with secondary hyperparathyroidism from vitamin D deficiency, kidney disease and other disorders.

 描述（由申请人提供）：原发性甲状旁腺功能亢进症 (PHPT) 是一种常见的内分泌疾病，其特征是甲状旁腺过度活跃和血钙水平升高，尽管据说 80% 的 PHPT 患者“无症状”（即缺乏症状）。肾结石和囊性纤维性骨炎的典型表现），这个术语用词不当，因为大多数患者报告有神经心理症状，包括记忆力和注意力下降。尽管高钙血症和甲状旁腺激素 (PTH) 升高都可能对认知产生影响，但大多数研究确实表明 PHPT 会产生神经心理后遗症，但甲状旁腺切除术 (PTX) 后的可逆性在各研究中并不一致。可能与一些研究中的小样本量和所检查的认知方面的变异性有关，由于这些限制，有认知症状的患者仍然被认为是“无症状”，并且认知功能障碍目前并不是一个适应症。这仍然是无症状 PHPT 治疗中最大的未解决问题，最近，我们通过验证工具表明 PHPT 中存在特定的认知功能障碍，并在手术治愈后得到改善，从而在这一具有挑战性的领域取得了进展。通过我们的工作证明 PHPT 中主动脉和颈动脉血管硬度的增加与 PTH 升高的程度相关，我们的新初步数据支持脑内血管系统中存在类似的 PTH 依赖性变化。这可能是 PHPT 认知障碍的基础。有研究表明，脑血流动力学功能障碍与血管性痴呆和颈动脉疾病的认知障碍有关。此外，最近的一项流行病学研究发现 PTH 升高是认知能力下降的危险因素。拟议的研究旨在确定上述 PTH 依赖性血管机制是否导致 PHPT 认知功能障碍，该过程是否可归因于 PTH 并可通过 PHPT 治愈而逆转，以及哪些大脑区域首先，我们将使用经颅多普勒来确认 PHPT 中脑内血管舒缩反应性 (VMR) 降低，并与 PTH 升高（但不是钙）和认知变化相关。其次，我们将确定受损的 VMR 是否是可逆的。最后，我们将使用 PTX 来识别大脑中受 PHPT 影响的部位。 这些研究的数据将解决第四届无症状 PHPT 国际会议（2013 年）的研究目标，该目标强调需要有关 PHPT 认知影响的数据，最终这些信息可能会导致手术指南的改变。此外，如果我们关于 PTH 依赖性脑血管功能和认知变化的假设得到证实，这些数据将对更广泛和更大的 PTH 过量患者群体产生影响，包括继发性患者。维生素 D 缺乏、肾脏疾病和其他疾病引起的甲状旁腺功能亢进。