Memory in Aging, Mild Cognitive impairment and AD

衰老、轻度认知障碍和 AD 中的记忆

• 批准号: 6943484
• 负责人: John M Olichney
• 金额: $ 26.88万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6943484
• 关键词: Alzheimer' s disease; aging; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; clinical research; cognition disorders; evoked potentials; functional magnetic resonance imaging; human old age (65+); human subject; longitudinal human study; memory; memory disorders; neural information processing; neuropsychological tests; semantics; time perception; time resolved data

The proposed studies, by a newly independent investigator, aim to further our understanding of the physiological bases of the memory impairments found with aging and in patients with memory disorders. We will use Event-Related Potentials (ERPs) and Functional-Magnetic Resonance Imaging (FMRI) to investigate verbal memory processes in aging, Mild Cognitive Impairment (MCI), and Alzheimer's disease (AD). The specific brain potentials of interest are the N400, a negativity which peaks near 400 msec post-stimulus, and the late positive component (LPC) which follows. The N400 amplitude is sensitive to the ease/difficulty with which the eliciting word is integrated with its semantic context. The LPC has been closely linked to memory processes. We have adapted our ERP word repetition paradigm, which utilizes repeating auditory context/visual target word pairs during a semantic categorization task, for use with FMRI. This paradigm provides electrophysiological measures of both implicit and explicit verbal memory processes, and may shed light on the neuroanatomical substrates of these processes. We have shown that amnesic patients have an abnormal reduced ERP repetition effect to "congruous" category-exemplar words (the "LPC repetition effect"). The degree of this reduction correlates well with severity of declarative memory impairment. We have recently found that patients with MCI also have a reduced LPC word repetition effect. Further, a severely reduced LPC repetition effect amplitude appears to increase the likelihood of subsequent conversion to AD. Our main specific aims are: 1) To quantify the decline in the ERP word repetition effects that occurs in normal aging. A reduced ERP word repetition effect may be a sensitive sign of memory impairment and pathological brain aging. 2) To test the sensitivity of our ERP and FMRI paradigms to mild AD and to "pre-clinical" AD. 3) To improve our understanding of which neural substrates generate the N400 and LPC in normal elderly and in patients with very early AD. Research design: Case-control and longitudinal studies and ERPs in conjunction with FMRI studies and selected behavioral measures. Methods: ERP and FMRI data will be obtained from normal, MCI, and AD subjects during semantic categorization. Repetition and congruity (degree of fit with a category) will be varied systematically to modulate the N400 and LPC. Comparisons of N400 and LPC characteristics will be made (between-and within- group) and related to memory and other cognitive abilities. Event-related FMRI BOLD response patterns will be used to constrain source dipole models for the neural generations of the N400 and LPC.

由一位新的独立研究者提出的研究旨在进一步了解随着年龄增长和记忆障碍患者的记忆障碍的生理基础。 我们将使用事件相关电位（ERPs）和功能磁共振成像（FMRI）来研究衰老、轻度认知障碍（MCI）和阿尔茨海默病（AD）中的言语记忆过程。 感兴趣的特定脑电位是N400，在刺激后400毫秒附近达到峰值的负性，以及随后的晚期正分量（LPC）。 N400波幅对引出词与其语义语境整合的难易程度敏感。 LPC与记忆过程密切相关。 我们已经调整了我们的ERP单词重复范式，它利用重复的听觉上下文/视觉目标词对在语义分类任务，与功能磁共振成像。 这种范式提供了内隐和外显言语记忆过程的电生理测量，并可能揭示这些过程的神经解剖学基础。 我们已经表明，健忘症患者有一个异常的减少ERP重复效应“一致”的类别范例的话（“LPC重复效应”）。 这种减少的程度与陈述性记忆障碍的严重程度密切相关。 我们最近发现，MCI患者也有减少LPC单词重复效应。 此外，严重降低的LPC重复效应幅度似乎增加了随后转换为AD的可能性。 我们的主要具体目标是：1）量化在正常老化中发生的ERP单词重复效应的下降。 ERP单词重复效应的降低可能是记忆障碍和病理性脑老化的敏感标志。 2)测试我们的ERP和功能磁共振成像范式的敏感性轻度AD和“临床前”AD。 3)提高我们对正常老年人和极早期AD患者中产生N400和LPC的神经基质的理解。研究设计：病例对照和纵向研究和ERP结合功能磁共振成像研究和选定的行为措施。 方法：采用ERP和FMRI技术对正常人、MCI和AD患者进行语义分类。重复和一致性（与类别的拟合程度）将系统地变化，以调节N400和LPC。 将进行N400和LPC特征的比较（组间和组内），并与记忆和其他认知能力相关。事件相关的功能磁共振成像BOLD响应模式将被用来约束源偶极子模型的N400和LPC的神经代。

项目成果

Phenotypes of hypofrontality in older female fragile X premutation carriers.

• DOI: 10.1002/ana.23933
• 发表时间: 2013-08
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Yang, Jin-Chen;Simon, Christa;Niu, Yu-Qiong;Bogost, Mark;Schneider, Andrea;Tassone, Flora;Seritan, Andreea;Grigsby, Jim;Hagerman, Paul J.;Hagerman, Randi J.;Olichney, John M.
• 通讯作者: Olichney, John M.

Abnormal N400 word repetition effects in fragile X-associated tremor/ataxia syndrome.

异常 N400 单词重复对脆性 X 相关震颤/共济失调综合征的影响。

• DOI: 10.1093/brain/awq077
• 发表时间: 2010
• 期刊: Brain : a journal of neurology
• 作者: Olichney,JohnM;Chan,Shiaohui;Wong,LingM;Schneider,Andrea;Seritan,Andreea;Niese,Adam;Yang,Jin-Chen;Laird,Kelsey;Teichholtz,Sara;Khan,Sara;Tassone,Flora;Hagerman,Randi
• 通讯作者: Hagerman,Randi

Abnormal semantic processing in females with fragile X-associated tremor/ataxia syndrome.

• DOI: 10.1111/gbb.12114
• 发表时间: 2014-02
• 期刊: Genes, brain, and behavior
• 作者: Yang JC;Simon C;Schneider A;Seritan AL;Hamilton L;Hagerman PJ;Hagerman RJ;Olichney JM
• 通讯作者: Olichney JM

From amnesia to dementia: ERP studies of memory and language.

• DOI: 10.1177/155005940703800106
• 发表时间: 2007-01-01
• 期刊: CLINICAL EEG AND NEUROSCIENCE
• 影响因子: 2
• 作者: Taylor, Jason R.;Olichney, John M.
• 通讯作者: Olichney, John M.

Test-retest reliability and stability of N400 effects: implications for the study of neuropsychiatric and cognitive disorders.

N400 效应的重测可靠性和稳定性：对神经精神和认知障碍研究的影响。

• DOI: 10.1016/j.clinph.2012.10.004
• 发表时间: 2013
• 期刊: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
• 作者: Olichney,John