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（由申请人提供）：人类大脑和认知方面的性别差异已得到充分记录，但目前尚不清楚男性和女性是否遵循与年龄相关的认知衰退的不同轨迹，确定男性和女性之间认知衰老差异的预测因素可能会导致男性和女性之间的差异认知衰老。开发针对性别的干预措施以促进两性成功的认知衰老，因为人类认知受到社会文化和环境因素的强烈影响，因此对非人类灵长类动物模型的研究可以最大限度地减少这种混杂因素，从而提供对认知衰老的深入了解。该应用程序使用特别适合神经认知衰老纵向评估的转化灵长类动物模型，即普通狨猴（Callithrix jacchus），其寿命约为 8 年，可以在其整个成年寿命中进行研究。此外，它们能够执行复杂的认知任务，并经历与人类相似的与年龄相关的大脑变化。该项目将纵向研究完整的雄性和雌性狨猴从中年到老年的情况。四年来，每年都会通过一系列认知、情感和运动测试来评估猴子的性别差异和与年龄相关的变化，每年还将使用磁共振成像检查性别差异和与年龄相关的大脑结构和功能连接变化。将分别分析具有认知障碍的老年猴子大脑中树突棘密度和形态、海马雌二醇水平和β-淀粉样蛋白沉积的性别差异。这项研究应该提供关于从中年到老年的转化灵长类动物模型中性别和年龄差异认知的生物学相关性的宝贵信息，这些数据将为理解性激素在认知中的作用奠定基础。最终，该项目应促进针对老年人认知障碍的针对性别的治疗方法。