Attention and Executive Functioning in Aging and Parkisonism

衰老和帕金森病中的注意力和执行功能

• 批准号: 8197776
• 负责人: JAY S SCHNEIDER
• 金额: $ 36.03万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197776
• 关键词: Acetylcholine; Adrenergic Agents; Affect; Age; Aging; Agonist; Anatomy; Animals; Attention; Behavioral; Biological Models; Brain region; Chronic; Clinical; Cognition; Cognitive; Cognitive deficits; Corpus striatum structure; Data; Disease; Doctor of Medicine; Dopamine; Dopaminergic Agents; Dose; Functional disorder; Glutamates; Health; Human; Impaired cognition; Intervention; Lead; Macaca mulatta; Memory; Memory impairment; Mental disorders; Modeling; Molecular Profiling; Monkeys; National Institute of Neurological Disorders and Stroke; Nature; Neurodegenerative Disorders; Neurologic; Neurons; Neurotoxins; Neurotransmitters; Nicotine; Nicotinic Agents; Nicotinic Receptors; Norepinephrine; Older Population; Opioid Peptide; Parkinson Disease; Parkinsonian Disorders; Pathology; Patients; Pharmaceutical Preparations; Pharmacotherapy; Process; Quality of life; Research; Resources; Risk Factors; Serotonin; Short-Term Memory; Staging; System; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Therapeutic Intervention; Translational Research; Treatment Efficacy; United States National Institutes of Health; Work; acetylcholine receptor agonist; age effect; age related; aged; aging population; brain behavior; cholinergic; clinically significant; cognitive function; drug discovery; drug efficacy; early onset; economic impact; effective therapy; endogenous opioids; executive function; gamma-Aminobutyric Acid; improved; insight; mature animal; nervous system disorder; neurobehavioral; neurochemistry; nonhuman primate; normal aging; older patient; pathological aging; receptor; receptor expression; relating to nervous system; response; restorative treatment; treatment strategy; young adult

DESCRIPTION (provided by applicant): Aging is a risk factor for cognitive impairment from a variety of causes and cognitive impairment is a well-recognized component of age-related neurodegenerative diseases such as Parkinson's disease (PD). While the effects of normal aging on memory have been studied in detail in non-human primates there have been few studies of the effects of age on attention and executive functioning, critical cognitive process for everyday functioning. No studies have examined cognitive status in a non-human primate model of parkinsonism in aged animals. This is important since aging is still the primary risk factor for developing PD and we need to better understand the impact of parkinsonian pathology on a baseline of age-related neurological changes. It is important to know, for example, the extent to which pharmacotherapies (such as nicotinic therapies) that are effective in ameliorating cognitive deficits in younger parkinsonian animals and in normal aged animals remain effective in aged parkinsonian animals with potentially different cognitive and nicotinic receptor profiles. The proposed research has the following specific aims: Specific Aim 1. Examine the effects of age and chronic low dose MPTP exposure on different components of attention and executive functioning (sustained attention, set shifting ability) and working memory (spatial working memory task with different loads on attention and memory) in rhesus macaques as they develop an early stage of parkinsonism; Specific Aim 2. Assess the potential therapeutic effects of sub-type selective nAChR agonists on attention, executive and memory dysfunctions described in Specific Aim 1; Specific Aim 3. Examine normal age-related and early Parkinson-related changes in neurochemistry and autoradiographic distribution of different nAChR subtypes in cortical and subcortical brain regions. The proposed studies will be the first to provide a detailed examination of the scope of the attention, executive function and memory deficits associated with aging and parkinsonism in non-human primates, relate these to alterations in nAChR subtype expression and distribution and test other potential ameliorative therapies. Work resulting from these studies will lead us toward developing improved therapies for age and PD-related cognitive dysfunctions and should help to minimize the effects of aging and PD on cognition, ultimately leading to an improved quality of life in the older population. Aging is a risk factor for cognitive impairment from a variety of causes and cognitive impairment is a well-recognized component of age-related neurodegenerative diseases such as Parkinson's disease (PD). While the effects of normal aging on memory have been studied in detail in non-human primates there have been few studies of the effects of age on other critical cognitive process for everyday functioning such as attention and executive functioning (or on potential therapeutic interventions) and no studies have examined cognitive status in a non-human primate model of parkinsonism in aged animals. Work resulting from the proposed studies will lead us toward developing improved therapies for age and PD-related cognitive dysfunctions and should help to minimize the effects of aging and PD on cognition, ultimately leading to an improved quality of life in the older population.

描述(申请人提供)：衰老是各种原因造成的认知障碍的风险因素，认知障碍是公认的与年龄相关的神经退行性疾病的组成部分，如帕金森氏病(PD)。虽然在非人类灵长类动物中详细研究了正常衰老对记忆的影响，但关于年龄对注意力和执行功能的影响的研究很少，而注意力和执行功能是日常功能的关键认知过程。还没有研究检验老年动物帕金森综合症的非人类灵长类动物模型的认知状态。这一点很重要，因为老龄化仍然是发展为帕金森病的主要危险因素，我们需要更好地了解帕金森病对与年龄相关的神经变化基线的影响。重要的是要知道，例如，在改善年轻帕金森病动物和正常老年动物的认知缺陷方面有效的药物疗法(如尼古丁疗法)在多大程度上仍然对认知和尼古丁受体特征可能不同的老年帕金森动物有效。建议的研究有以下特定目的：特定目的1.检测年龄和长期低剂量MPTP暴露对恒河猴早期帕金森病的注意力和执行功能(持续注意、定势转移能力)和工作记忆(不同负荷的空间工作记忆任务)的不同组成部分的影响；特定目的2.评估特定类型选择性nAChR激动剂对特定目标1所述的注意力、执行和记忆功能障碍的潜在治疗作用；特定目的3.检测正常年龄相关和早期帕金森相关的神经化学变化和不同nAChR亚型在皮质和皮质下脑区的放射自显影分布。这项拟议的研究将首次详细检查与衰老和帕金森症相关的非人类灵长类动物的注意力、执行功能和记忆缺陷的范围，将这些与nAChR亚型表达和分布的变化联系起来，并测试其他潜在的改善疗法。这些研究的结果将引导我们为年龄和PD相关的认知功能障碍开发更好的治疗方法，并应有助于将老龄化和PD对认知的影响降至最低，最终提高老年人的生活质量。衰老是各种原因导致认知障碍的危险因素，认知障碍是公认的与年龄相关的神经退行性疾病的组成部分，如帕金森氏病(PD)。虽然在非人类灵长类动物中详细研究了正常衰老对记忆的影响，但很少有关于年龄对日常功能的其他关键认知过程的影响的研究，如注意力和执行功能(或潜在的治疗干预)，也没有研究检验老年动物帕金森综合症的非人类灵长类动物模型的认知状态。拟议研究的工作将引导我们开发针对年龄和帕金森病相关认知功能障碍的改进治疗方法，并应有助于将衰老和帕金森病对认知的影响降至最低，最终提高老年人的生活质量。

项目成果

Attention, executive functioning and memory in normal aged rhesus monkeys.

正常老年恒河猴的注意力、执行功能和记忆力。

• DOI: 10.1016/j.bbr.2010.12.021
• 发表时间: 2011
• 期刊: Behavioural brain research
• 影响因子: 2.7
• 作者: Zeamer,Alyson;Decamp,Emmanuel;Clark,Kathryn;Schneider,JS
• 通讯作者: Schneider,JS