Visual-somatosensory integration as a novel marker of Alzheimer's disease

摘要 识别新的、非认知的（即，感觉或运动），阿尔茨海默病的非侵入性标志物， 相关痴呆症是国家阿尔茨海默病计划确定的国家优先事项。越来越多的证据表明 阿尔茨海默病的病理表现在感觉关联区， 参与记忆功能。以前的调查未能审查的相互作用和时间进程， 感觉、认知和运动功能障碍对阿尔茨海默病进展的影响。能够成功 在多种感觉形式中整合多感觉信息是功能和移动性重要方面 在真实的世界里我们的研究表明，多感觉整合可以作为一种新的标记， 临床前阿尔茨海默病的视觉-躯体感觉的幅度之间的关联 整合和重要的认知（注意力）和运动（平衡、步态和福尔斯）结果。我们强调了 痴呆症和轻度认知障碍对这些关系的不利影响，但潜在的 功能和神经解剖学网络仍有待发现。识别这些功能网络是 对于指导未来基于多感官的干预措施的发展至关重要，以防止非认知结果， 就像认知障碍者的福尔斯一样。因此，我们建议招募208名居住在社区的老年人 有和没有临床前阿尔茨海默病（定义为神经心理学上的认知功能受损 检测和血浆中是否存在腺苷酸）进行为期三年的纵向观察研究。我们的核心假设 临床前阿尔茨海默病与皮层下和皮层区域的神经破坏有关， 同时调节多感觉、认知和运动功能，导致活动能力下降。我们的战略 实验设计，利用现有的纵向队列，旨在评估多感官的有效性， 整合作为临床前阿尔茨海默病的行为标记。它也提供了一个机会， 个体感觉、运动和认知过程的综合时间过程和相互作用（及其 相互作用）在临床前阿尔茨海默病。拟议的项目解决了NIH的优先事项，以及 NIA的特殊利益通知[NOT-AG-20-053]。这项工作将增加对神经生物学的理解， 阿尔茨海默病，并将指导未来的多传感器为基础的干预研究，旨在减轻残疾 并在有或没有临床前阿尔茨海默病的老年人中保持独立。 2

ABSTRACT Identification of novel, non-cognitive (i.e., sensory or motor), non-invasive markers of Alzheimer’s disease and related dementias are a national priority identified by the National Alzheimer Plan. Growing evidence suggests that Alzheimer’s pathology manifests in sensory association areas well before appearing in neural regions involved in memory function. Previous investigations have failed to examine the interplay and time course of sensory, cognitive, and motor dysfunction on the progression of Alzheimer’s disease. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of functioning and mobility in the real world. Our research suggests that multisensory integration could be used as a novel marker for preclinical Alzheimer’s disease given reported associations between magnitude of visual-somatosensory integration and important cognitive (attention) and motor (balance, gait, and falls) outcomes. We have highlighted the adverse effects of dementia and mild cognitive impairment on these relationships, but the underlying functional and neuroanatomical networks remain to be uncovered. Identification of these functional networks is critical to guide development of future multisensory-based interventions to prevent non-cognitive outcomes such as falls in cognitively impaired individuals. Hence, we propose to recruit 208 community-dwelling older adults with and without preclinical Alzheimer’s disease (defined as impaired cognitive function on neuropsychological testing and presence of Aß in plasma) for a three-year longitudinal observational study. Our central hypothesis is that preclinical Alzheimer’s disease is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions, resulting in mobility decline. Our strategic experimental design, which leverages existing longitudinal cohorts, aims to assess the validity of multisensory integration as a behavioral marker for preclinical Alzheimer’s disease. It also provides an opportunity to examine the integrative time course and interplay of individual sensory, motor, and cognitive processes (and their interactions) in preclinical Alzheimer’s disease. The proposed project addresses the NIH’s priority, as well as NIA’s special interest notice [NOT-AG-20-053]. This work will increase understanding of the neurobiology of Alzheimer’s disease and will guide future multisensory-based intervention studies that aim to alleviate disability and maintain independence in older adults with and without preclinical Alzheimer’s disease. 2