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

创建猴子迷你精神状态检查 (mMMSE)，用于识别与阿尔茨海默病和相关痴呆症相关的早期认知缺陷

• 批准号: 10512472
• 负责人: Eliza Bliss-Moreau
• 金额: $ 33.18万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10512472
• 关键词: 19 year old; Affective; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease related dementia; Animal Model; Animals; Behavioral; Behavioral Symptoms; Biological; Biological Markers; California; Cardiac; Caring; Cognitive; Cognitive aging; Cognitive deficits; Cross-Sectional Studies; Dementia; Disease; Early Intervention; Enrollment; Ensure; Exercise; Genetic study; Goals; Gold; Health; Hour; Human; Individual; Individual Differences; Intervention; Laboratories; Light; Literature; Longevity; Longitudinal Studies; Longitudinal cohort study; Macaca mulatta; Maintenance; Measures; Memory; Mental Health; Modeling; Monkeys; Neurodegenerative Disorders; Outcome; Pathology; Performance; Personal Satisfaction; Persons; Phase; Primates; Process; Research; Research Personnel; Resources; Risk; Running; Sampling; Sampling Studies; Screening procedure; Structure; Study models; Subgroup; Testing; Time; Training; Variant; Work; age related; base; cognitive function; cognitive testing; disorder risk; emotional experience; exercise intervention; experience; experimental study; functional status; high throughput screening; human old age (65+); improved; indexing; insight; mental state; nonhuman primate; pathological aging; physical conditioning; psychologic; psychological symptom; screening; social; social relationships; therapy development; tool; tool development; treadmill

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.

衰老是一个变化很大的过程。有些人的年龄很好，有持续的记忆力，通常是积极的情感体验，健康的社会关系，以及老年时的良好身体健康，而另一些人则经历了与年龄相关的心理和身体健康的显著改善。预测谁容易受到不良老化结果的影响，特别是阿尔茨海默病和阿尔茨海默病相关痴呆（AD/ADRD），对于制定早期干预措施和在最有效的时间范围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于了解衰老轨迹和易受AD/ADRD病理影响的因果生物学机制，目的是开发治疗和干预措施以促进人类健康。这种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遗传研究或研究自然发生的变异。拟议项目的灵感来自人类文献，其中有许多快速，资源轻的筛选工具，用于整个生命周期的心理健康，其中简易精神状态检查（MMSE）是最受欢迎的预测认知老化结果的工具之一，并预测AD/ADRD的存在/发生。拟议的工作开发了一种猴子版本的MMSE（mMMSE）-一种高通量筛选工具，用于测量各种领域的认知功能以及广泛涉及痴呆症的行为和心理症状的社会和情感处理。有效性将通过跨心理领域的“黄金标准”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，将神经退行性疾病风险的生物标志物与功能状态相关联，识别脆弱猴子的亚组，并通过识别健康状况不佳的猴子来增强对老化非人灵长类动物群体的维护。了解非人灵长类动物的衰老轨迹并制定干预措施以促进其健康，对于维持衰老猴群作为国家资源至关重要，并且还使这些猴子成为研究人类健康和年龄相关疾病（如AD/ADRD）的适当动物模型。