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

视觉体感整合作为阿尔茨海默病的新标志

• 批准号: 10560644
• 负责人: Jeannette R. Mahoney
• 金额: $ 84万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560644
• 关键词: Address; Adverse effects; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid beta-Protein; Area; Area Under Curve; Attention; Basal Ganglia; Behavioral; Behavioral Model; Brain; Clinic; Cognitive; Communities; Data; Dementia; Deposition; Development; Disease; Disease Marker; Disease Progression; Elderly; Equilibrium; Experimental Designs; Fostering; Functional Magnetic Resonance Imaging; Funding; Future; Gait; Impaired cognition; Individual; Infrastructure; Intervention; Intervention Studies; Investigation; Link; Longitudinal Studies; Longitudinal cohort; Longitudinal, observational study; Magnetic Resonance Imaging; Measures; Mediating; Memory; Modality; Motor; National Institute on Alcohol Abuse and Alcoholism; Neuroanatomy; Neurobiology; Neuropsychological Tests; Outcome; Parietal; Participant; Performance; Peripheral; Plasma; Positron-Emission Tomography; Prefrontal Cortex; Process; Reaction Time; Recording of previous events; Reporting; Research; Research Priority; Resources; Sensory; Statistical Models; Structure of superior frontal gyrus; Thick; Time; United States National Institutes of Health; Visual; Work; abeta accumulation; blood oxygen level dependent; cognitive function; cognitive process; disability; fall risk; falls; functional independence; innovation; insight; interest; longitudinal design; mild cognitive impairment; motor disorder; multisensory; neural; neural correlate; neural network; novel; novel marker; pre-clinical; prevent; recruit; response; sensory input; sensory integration; somatosensory; therapy design

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

摘要 识别阿尔茨海默病的新的、非认知的(即，感觉或运动)、非侵入性标记和 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联系区域，而不是出现在神经区域 参与记忆功能。之前的调查未能检查出 感觉、认知和运动功能障碍对阿尔茨海默病进展的影响。取得成功的能力 跨多个感觉模式整合多感觉信息是功能和移动性的重要方面 在真实的世界见面。我们的研究表明，多感觉整合可以作为一种新的标记物。 临床前阿尔茨海默病已报道的视觉-躯体感觉强度之间的关联 整合和重要的认知(注意力)和运动(平衡、步态和跌倒)结果。我们已经强调了 痴呆症和轻度认知障碍对这些关系的不利影响，但潜在的 功能和神经解剖网络仍未被发现。这些功能网络的标识是 对指导未来基于多感觉的干预措施的发展至关重要，以防止非认知结果 在认知受损的人身上也是如此。因此，我们建议招募208名社区居住的老年人 有无临床前阿尔茨海默病(定义为神经心理上的认知功能受损 进行了为期三年的纵向观察研究。我们的中心假设 临床前阿尔茨海默病与皮质下和皮质区的神经紊乱有关 同时调节多感觉、认知和运动功能，导致行动能力下降。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物。它还提供了一个机会来研究 个体感觉、运动和认知过程的综合时间进程和相互作用(及其相互作用 相互作用)在临床前阿尔茨海默病中。拟议的项目涉及国家卫生研究院的优先事项，以及 NIA的特别利益通知[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，并将指导未来旨在减轻残疾的基于多感官的干预研究 并在患有和不患有临床前阿尔茨海默病的老年人中保持独立性。 2.