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: 10683330
• 负责人: Eliza Bliss-Moreau
• 金额: $ 31.74万
• 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/10683330
• 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; Correlation Studies; Dementia; Disease; Early Intervention; Early identification; Enrollment; Exercise; Genetic study; Goals; 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; cognitive function; cognitive testing; disorder risk; emotional experience; exercise intervention; experience; experimental study; functional status; high throughput screening; human old age (65+); improved; indexing; individual variation; 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，有些人在老年时记忆力持续良好，通常具有积极的情感体验、健康的社会关系和良好的身体健康，而另一些人则在心理和身体健康方面经历了与年龄相关的严重损害。容易受到不良衰老结果的影响，特别是阿尔茨海默病和阿尔茨海默病相关痴呆症（AD/ADRD）对于早期干预和在长期使用非人类灵长类动物模型最有效的时间范围内部署治疗至关重要。了解衰老轨迹和 AD/ADRD 病理脆弱性的因果生物学机制，目的是开发促进人类健康的治疗和干预措施，此类研究特别具有挑战性，因为这些领域的实验测试需要大量培训（通常为 6-18 岁）。几个月），排除了使用大样本进行基因研究或自然发生变异的研究。拟议的项目受到人类文献的启发，其中有许多快速、资源丰富的针对整个生命周期心理健康的筛查工具。简易精神状态检查(MMSE) 是最流行的预测认知衰老结果的方法之一，可预测 AD/ADRD 的存在/发生。拟议的工作开发了猴子版本的 MMSE (mmMSE)——一种用于测量认知功能的高通量筛选工具。该工具将通过跨心理领域的“黄金标准”时间密集型任务来建立广泛涉及痴呆症行为和心理症状的社会和情感处理。大样本研究将神经退行性疾病风险的生物标志物与功能状态相关联，识别易受伤害的猴子亚群，并通过识别处于健康状况不佳风险的猴子来加强对衰老非人类灵长类动物群体的维护，并制定干预措施以促进其健康。对于维持老龄猴群作为国家资源以及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适当动物模型至关重要。