Sex differences in cognitive and brain aging: a primate model

描述（由申请人提供）：人类大脑和认知的性别差异已被充分记录，但男性和女性在与年龄相关的认知衰退中是否遵循不同的轨迹仍不清楚。识别男性和女性认知衰老差异的预测因素可能会导致性别特异性干预措施的发展，以促进两性认知衰老的成功。由于人类认知受到社会文化和环境因素的强烈影响，在非人类灵长类动物模型中进行的研究可以将这种混淆最小化，可以为认知衰老中性别差异的生物学基础提供相当大的见解。该应用程序使用了一种翻译灵长类动物模型，该模型特别适合于对神经认知老化的纵向评估，即普通狨猴（Callithrix jacchus）。狨猴的寿命约为8年，可以在它们整个成年期进行研究。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。该项目将从中年到老年纵向研究完整的雄性和雌性狨猴。在四年的时间里，研究人员每年都会对猴子进行一系列认知、情感和运动测试，以评估性别差异和年龄相关的变化。性别差异和年龄相关的大脑结构和功能连接变化也将分别每年使用磁共振成像（MRI）和静息状态功能磁共振成像（fMRI）进行检查。树突棘密度和形态、海马雌二醇水平和-淀粉样蛋白沉积的性别差异将在认知受损或未受损的老年猴子的大脑中进行分析。这项研究将为从中年到老年的灵长类动物模型中认知的性别和年龄差异的生物学相关性提供宝贵的信息。这些数据将成为理解性激素在神经认知老化中的作用的基础。最终，该项目应促进对老年人认知障碍的管理采取针对不同性别的方法。

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.