Sex differences in cognitive and brain aging: a primate model

认知和大脑衰老的性别差异：灵长类动物模型

• 批准号: 8912966
• 负责人: Agnes Lacreuse
• 金额: $ 31.22万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912966
• 关键词: Adult; Age; Age-associated memory impairment; Aging; Amyloid deposition; Animals; Behavioral; Biological; Brain; Callithrix; Callithrix jacchus jacchus; Cognition; Cognitive; Cognitive aging; Complex; Data; Dementia; Dendritic Spines; Emotional; Environmental Risk Factor; Estradiol; Female; Foundations; Functional Magnetic Resonance Imaging; Gonadal Steroid Hormones; Health; Hippocampus (Brain); Human; Impaired cognition; Intervention; Lead; Life; Longevity; Magnetic Resonance Imaging; Measures; Modeling; Monkeys; Morphology; Motor; Neurocognitive; Physiological; Primates; Rest; Role; Sex Characteristics; Sexual Development; Structure; Testing; Woman; age difference; age related; aged; aging brain; awake; base; brain morphology; brain volume; cognitive task; density; experience; insight; male; men; middle age; neuroimaging; nonhuman primate; sex; successful intervention

DESCRIPTION (provided by applicant): Sex differences in human brain and cognition are well documented, but it remains unclear whether men and women follow different trajectories of age-related cognitive decline. Identifying predictors of differential cognitive aging between men and women could lead to the development of sex-specific interventions to promote successful cognitive aging in both sexes. Because human cognition is strongly influenced by socio- cultural and environmental factors, studies in nonhuman primate models, for which such confounds can be minimized, can provide considerable insight into the biological bases of sex differences in cognitive aging. This application uses a translational primate model uniquely suited for longitudinal assessments of neurocognitive aging, the common marmoset (Callithrix jacchus). With a lifespan of about 8 years, marmosets can be studied throughout their entire adult lifespan. In addition, they are able to perform complex cognitive tasks and experience age-related brain changes that resemble those of humans. This project will study intact male and female marmosets longitudinally from middle-age to old age. Sex differences and age-related changes will be assessed in monkeys tested annually for four years on a battery of cognitive, emotional and motor tests. Sex differences and age-related changes in brain structure and functional connectivity will also be examined annually using Magnetic Resonance Imaging (MRI) and resting- state functional MRI (fMRI), respectively. Sex differences in dendritic spine density and morphology, hippocampal estradiol levels and �-amyloid deposition will be analyzed in the brains of aged monkeys characterized as cognitively impaired or unimpaired. This study should provide invaluable information on the biological correlates of sex and age differences in cognition in a translational primate model followed from middle-age to old age. The data will serve as a fundamental foundation for understanding the role of sex hormones in neurocognitive aging. Ultimately, the project should promote sex-specific approaches to the management of cognitive impairment in older people.

描述（由适用提供）：人类脑和认知的性别差异已得到充分记录，但尚不清楚男人和女人是否遵循与年龄相关的认知下降的不同轨迹。确定男性和女性不同认知衰老的预测因素可能会导致性别特异性干预措施的发展，以促进两性的成功认知衰老。由于人类认知受社会文化和环境因素的强烈影响，因此可以将这种混杂的非人类灵长类动物模型的研究最小化，可以提供对认知衰老中性别差异的生物学基础的考虑。该应用使用翻译的主要模型独特地适合于神经认知衰老的纵向评估，即通用的果果（Callithrix jacchus）。寿命约为8年，可以在整个成年人的整个寿命中进行研究。此外，他们能够执行复杂的认知任务并体验与人类相似的年龄相关的大脑变化。该项目将从中年到老年进行纵向研究完整的男性和雌性摩尔果。性别差异和与年龄相关的变化将在每年测试的猴子中评估四年，以一系列认知，情感和运动测试进行评估。性别差异和与年龄相关的大脑结构和功能连通性的变化也将分别使用磁共振成像（MRI）和静止状态功能性MRI（fMRI）进行检查。在树突状脊柱密度和形态，海马雌二醇水平和 - 淀粉样蛋白沉积中的性别差异将在具有认知障碍或单位的年龄猴子的大脑中进行分析。这项研究应提供有关从中年到老年的转化私人模型中性别和年龄差异的生物学相关性的宝贵信息。这些数据将成为理解性马在神经认知衰老中的作用的基本基础。最终，该项目应促进特定于性别的方法来管理老年人的认知障碍。