在人类中,认知老化是高度可变的,一些人经历下降,而另一些人保持稳定,和不同的认知领域表现出不均匀的衰老脆弱性。驱动这种个体内和个体间变异性的神经机制尚未完全理解,在翻译模型中进行纵向研究对于阐明所涉及的时间表和过程至关重要。普通的马墨塞特(Callithrixjacchus),一个短暂的非人灵长类动物,提供了前所未有的机会,可以在浓缩的时间范围内对衰老和与年龄有关的疾病进行纵向调查,在高度可翻译的动物模型中。作为认知衰老的模型的潜力是无可争议的,但是,为纵向衰老研究量身定制的全面认知电池尚未开发,应用,或已验证。这代表了一个关键的缺失部分,用于评估作为模型的mar猴,并了解mar猴认知衰老在多大程度上反映了人类中发现的模式,包括在与年龄相关的认知能力下降的脆弱性上,猿猴是否具有个体差异。为了解决这个问题,我们开发了一个全面的基于触摸屏的神经心理学测试电池,针对五个认知领域:工作记忆,刺激-奖励联想学习,认知灵活性,电机速度,和动机。我们测试了一大群猴,从年轻人到老年病学,几年来。我们发现认知老化有显著的变异性,最大的下降发生在依赖于前额叶皮层和海马的区域。此外,我们观察到个体间对年龄相关认知能力下降的脆弱性的显著差异:一些猿猴在多个领域下降,其他人只有一个,有些人根本没有下降。这种模式反映了人类认知老化,巩固了马墨赛作为与年龄相关的认知能力下降的有利模型,并为识别所涉及的神经机制提供了坚实的基础。
In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in
translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.