Neuromarkers of age-related cognitive decline

与年龄相关的认知能力下降的神经标志物

• 批准号: 8091223
• 负责人: Robert H Paul
• 金额: $ 55.25万
• 依托单位: UNIVERSITY OF MISSOURI-ST. LOUIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8091223
• 关键词: Accounting; Address; Adult; Affect; Age; Age-associated memory impairment; Aging; Angiotensinogen; Anisotropy; Arylesterase; Biological Markers; Blood Vessels; Brain; Brain region; C-reactive protein; Candidate Disease Gene; Cardiovascular Diseases; Characteristics; Cognitive; Cognitive aging; Cross-Sectional Studies; Data; Databases; Development; Diabetic Angiopathies; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Elderly; Evolution; Fiber; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Goals; Heritability; Image; Impaired cognition; Individual; Inflammation; Injury; Interleukin-6; International; Learning; Length; Longevity; Magnetic Resonance Imaging; Maps; Measures; Medial; Methods; Metric; Modeling; Neurocognitive; Neurologic; Performance; Proteins; Recruitment Activity; Research Personnel; Role; Speed; Stroke; Structure; Systemic disease; TNF gene; Temporal Lobe; Tumor Necrosis Factor-alpha; Twin Multiple Birth; Twin Studies; Variant; Vascular Diseases; Work; age group; age related; age related cognitive change; aryldialkylphosphatase; base; brain volume; cognitive change; cognitive function; cohort; comparison group; executive function; genetic risk factor; gray matter; healthy aging; human TNF protein; indexing; neuroimaging; neuropsychological; novel; programs; theories; vascular inflammation; white matter

DESCRIPTION (provided by applicant): The purpose of the present study is to investigate relationships between novel neuroimaging markers based on DTI fiber tracking models, genetic polymorphisms of vascular disease and inflammation, and age-related cognitive decline in healthy individuals. Recent studies, including data from our lab, indicate that the integrity of the subcortical white matter as measured by diffusion tensor imaging (DTI) and subcortical hyperintensities on structural MRI are important correlates of age-related cognitive differences. Cortical brain volume changes also account for some variance in cognitive function among the elderly, however our data suggest that alterations in the subcortical white matter more strongly correlate with cognitive status. In addition, studies have demonstrated that white matter alterations in the elderly are heritable, implicating the role of genetic factors in the development of mild ischemic changes and associated inflammation. In this revised application we provide compelling new pilot data demonstrating the role of genetic polymorphisms for vascular injury on both imaging and cognitive indices. We also provide new data from our recent work demonstrating the sensitivity of our novel DTI metrics based on quantified fiber tracking models to explain variance in cognitive aging. These novel metrics allow us to examine the impact of changes in quantified fiber lengths on cognitive function. In the present study we will extend these preliminary studies and examine relationships between DTI and structural MRI, genetic polymorphisms associated with microvascular disease (angiotensinogen, paroxonase) and related CMS inflammation (C-reactive protein, IL- 6, TNF-a), and cognitive status in the healthy elderly. The study will capitalize on an existing database containing genetic and neurocognitive data on more than 1,000 individuals stratified in five groups from age 31-80 (n = 200/group). Neuroimaging data is currently available for 200 of these individuals and we will recruit an additional 120 individuals between the ages of 51-80 to supplement the older age spectrum and obtain novel fiber tracking maps from the DTI data. Newly recruited individuals will be followed longitudinally to examine the evolution and progression of white matter and cognitive abnormalities in the context of genetic risk factors. Group comparisons and latent variable modeling will be conducted to examine relationships between the neuroimaging indices, genetic polymorphisms, and differences in cognitive function in older healthy adults. The present study will be the first to integrate these approaches to examine a model of age-related cognitive decline implicating the subcortical white matter. The results will significantly inform our understanding of cognitive aging.

描述（由申请人提供）：本研究的目的是研究基于 DTI 纤维追踪模型的新型神经影像标记、血管疾病和炎症的遗传多态性以及健康个体中与年龄相关的认知衰退之间的关系。最近的研究，包括我们实验室的数据，表明通过扩散张量成像 (DTI) 测量的皮质下白质的完整性和结构 MRI 上的皮质下高信号是与年龄相关的认知差异的重要相关性。皮质脑容量的变化也解释了老年人认知功能的一些差异，然而我们的数据表明，皮质下白质的变化与认知状态的相关性更强。此外，研究表明，老年人的白质改变是可遗传的，这表明遗传因素在轻度缺血性变化和相关炎症的发展中发挥着作用。在这个修订后的应用程序中，我们提供了令人信服的新试验数据，证明了遗传多态性对血管损伤在成像和认知指数上的作用。我们还提供了我们最近工作中的新数据，证明了我们基于量化纤维跟踪模型的新颖 DTI 指标的敏感性，以解释认知衰老的差异。这些新颖的指标使我们能够检查量化纤维长度的变化对认知功能的影响。在本研究中，我们将扩展这些初步研究，并检查 DTI 和结构 MRI 之间的关系、与微血管疾病（血管紧张素原、帕氧磷酶）和相关 CMS 炎症（C 反应蛋白、IL-6、TNF-a）相关的遗传多态性以及健康老年人的认知状况。该研究将利用现有数据库，其中包含 1,000 多名年龄在 31-80 岁之间的人的遗传和神经认知数据，分为五组（n = 200/组）。目前可获得其中 200 名个人的神经影像数据，我们将另外招募 120 名年龄在 51-80 岁之间的个人，以补充老年谱，并从 DTI 数据中获取新颖的纤维跟踪图。新招募的个体将被纵向跟踪，以检查遗传风险因素背景下白质和认知异常的进化和进展。将进行组比较和潜在变量建模，以检查老年健康成年人的神经影像指数、遗传多态性和认知功能差异之间的关系。本研究将是第一个整合这些方法来检查涉及皮质下白质的与年龄相关的认知衰退模型的研究。研究结果将极大地促进我们对认知衰老的理解。

项目成果

The impact of human immune deficiency virus and hepatitis C coinfection on white matter microstructural integrity.

• DOI: 10.1007/s13365-015-0409-0
• 发表时间: 2016-06
• 期刊: Journal of neurovirology
• 影响因子: 3.2
• 作者: Heaps-Woodruff JM;Wright PW;Ances BM;Clifford D;Paul RH
• 通讯作者: Paul RH

Kernel regression estimation of fiber orientation mixtures in diffusion MRI.

• DOI: 10.1016/j.neuroimage.2015.11.061
• 发表时间: 2016-02-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Cabeen RP;Bastin ME;Laidlaw DH
• 通讯作者: Laidlaw DH

Impact of early vs. late childhood early life stress on brain morphometrics.

• DOI: 10.1007/s11682-012-9215-y
• 发表时间: 2013-06
• 期刊: Brain imaging and behavior
• 影响因子: 3.2
• 作者: Baker LM;Williams LM;Korgaonkar MS;Cohen RA;Heaps JM;Paul RH
• 通讯作者: Paul RH

A Comparative evaluation of voxel-based spatial mapping in diffusion tensor imaging.

• DOI: 10.1016/j.neuroimage.2016.11.020
• 发表时间: 2017-02-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Cabeen RP;Bastin ME;Laidlaw DH
• 通讯作者: Laidlaw DH