Creation of a monkey mini mental state exam (mMMSE) for identifying early cognitive deficits related to Alzheimer’s disease and related dementias

衰老是一个变数很大的过程。有些人衰老得很好，有持续的记忆力、通常积极的情感体验、健康的社会关系和良好的身体健康，而另一些人则经历了与年龄相关的严重损害心理和身体健康的情况。预测谁容易受到不良老龄化结局，特别是阿尔茨海默病和阿尔茨海默病相关痴呆(AD/ADRD)的影响，对于制定早期干预措施并在最有效的时间框架内部署治疗至关重要。长期以来，非人灵长类动物模型一直被用来理解衰老轨迹和AD/ADRD病理易感性背后的因果生物学机制，目的是开发治疗和干预措施以促进人类健康。这类研究特别具有挑战性，因为这些领域的实验测试需要广泛的培训(通常为6-18个月)，排除了使用大样本进行基因研究或自然发生变异研究的可能性。该项目的灵感来自人类文献，这些文献有许多快速、资源少的终生心理健康筛查工具，其中迷你精神状态检查(MMSE)是最受欢迎的预测认知衰老结果的工具之一，并可预测AD/ADRD的存在/发生。这项拟议的工作开发了一种猴子版的MMSE(MMMSE)-一种高通量筛查工具，用于测量各种领域的认知功能以及社交和情感处理，这些处理被广泛认为是痴呆症的行为和心理症状。效度将通过跨心理领域的时间密集型任务来建立。该工具将允许对大样本研究进行快速认知评估，这些研究将神经退行性疾病风险的生物标记物与功能状态关联起来，识别易受攻击的猴子亚群，并通过识别健康状况不佳的猴子来加强对老化的非人类灵长类群体的维护。了解非人类灵长类动物的衰老轨迹并开发促进它们福祉的干预措施，对于维持老龄猴子群体作为国家资源至关重要，也对于让这些猴子成为研究人类健康和AD/ADRD等与年龄相关的疾病的合适动物模型至关重要。

Aging is a hugely variable process. Some people age well, with sustained memory, generally positive emotional experiences, healthy social relationships, and good physical health into old age, while others experience significant age-related detriments to both psychological and physical health. Predicting who is vulnerable to poor aging outcomes and specifically to Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) is critical for developing early interventions and deploying treatments in a timeframe in which they are most efficacious. Nonhuman primate models have long been used to understand the causal biological mechanisms underlying aging trajectories and vulnerability to AD/ADRD pathology, with the goal of developing treatments and interventions to promote human health. Such research is particularly challenging because the experimental testing in these domains requires extensive training (typically 6-18 months), precluding the use of large samples that would allow for genetic studies or studies of naturally occurring variation. The proposed project is inspired by human literature which has a number of quick, resource-light screening tools for psychological health across the lifespan, of which the Mini Mental State Examination (MMSE) is one of the most popular to predict cognitive aging outcomes and are predictive to the presence/occurrence of AD/ADRD. The proposed work develops a monkey version of MMSE (the mMMSE) – a high throughput screening tool to measure cognitive functions across a variety of domains as well as social and affective processing which are broadly implicated as behavioral and psychological symptoms of dementia. Validity will be established via “gold standard” time-intensive tasks across psychological domains. This tool will allow for rapid cognitive assessment for large sample studies correlating biomarkers of neurodegenerative disease risk with functional status, identification of subgroups of vulnerable monkeys, and enhanced maintenance of aging nonhuman primate colonies by identifying monkeys at risk of poor health. Understanding nonhuman primate aging trajectories and developing interventions to promote their well-being is critical to maintain colonies of aging monkeys as a national resource and also to have those monkeys be appropriate animal models for the study of human health and age-related diseases like AD/ADRD.