心理科学进展, 2019, 27(1): 51-59 doi: 10.3724/SP.J.1042.2019.00051

研究前沿

主观记忆减退老年人情节记忆的行为表现及其脑机制

尹述飞,1, 李添1, 朱心怡2,3

1 湖北大学教育学院心理学系, 武汉 430062

2 中国科学院心理健康重点实验室(中国科学院心理研究所)老年心理研究中心, 北京 100101

3 中国科学院大学心理学系, 北京 100049);

Episodic memory performance and underlying brain mechanisms in elderly with subjective memory decline

YIN Shufei,1, LI Tian1, ZHU Xinyi2,3

1 Department of Psychology, Faculty of Education, Hubei University, Wuhan 430062, China

2 Center on Aging Psychology, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China

3 Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China

通讯作者: 尹述飞, E-mail: yinshufei121@163.com

收稿日期: 2017-12-22   网络出版日期: 2019-01-15

基金资助: * 国家自然科学基金青年基金.  31600904
湖北省教育厅人文社会科学研究青年基金.  18Q017
湖北省高校人文社科重点基地:湖北大学农村社区研究中心开放基金.  0440390108
湖北大学自然科学基金青年项目.  170016

Received: 2017-12-22   Online: 2019-01-15

摘要

情节记忆是个体对特定时间,特定地点所经历的特定事件的记忆.主观报告情节记忆下降是主观记忆减退老年人最典型的表现.与健康对照组老年人相比, 主观记忆减退老年人情节记忆下降的速率更快, 罹患老年性痴呆的风险更高, 但其情节记忆加工的脑机制尚不明确.前人研究提示, 主观记忆减退老年人在外在记忆行为尚未出现损伤的情况下, 其大脑情节记忆相关脑区的神经活动已经出现异常.探究主观记忆减退的记忆神经环路关键节点和路径的异常, 揭示神经环路在老年痴呆发生发展中的变化规律, 对深入理解老年痴呆的发病机制有重要的科学意义.同时, 主观记忆减退老年人作为特殊的记忆损伤群体, 对其神经环路的深入探究, 也必将为揭示人类记忆的神经机制做出独特的贡献.

关键词: 情节记忆 ; 主观记忆减退 ; 老年性痴呆 ; 脑机制 ; 老年人

Abstract

Episodic memory (EM) is the collection of past personal experiences that have occurred at a particular time and place. Subjective decline in EM is reported in the elderly with subjective memory decline (SMD). The elderly with SMD have a faster rate of EM decline and a higher risk of developing Alzheimer's disease (AD) than do healthy controls. However, the brain mechanisms of episodic memory impairment in SMD are unclear. Previous studies suggest that even when memory performance has no observable deficits, the brain structure and function associated with EM have been abnormal in SMD. Two further studies are of vital scientific significance for understanding the pathogenesis of AD. One is to explore the abnormal key nodes and paths of memory neural circuits in SMD. The other is to reveal the changes in the neural circuits in the progression of AD. In addition, considering that the elderly with SMD are a special group with memory impairment, an in-depth investigation into the neural circuits in this group, will make a unique contribution to revealing the neural mechanism of human memory.

Keywords: episodic memory ; subjective memory decline ; Alzheimer's disease ; brain mechanisms ; elderly

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本文引用格式

尹述飞, 李添, 朱心怡. (2019). 主观记忆减退老年人情节记忆的行为表现及其脑机制 . 心理科学进展, 27(1), 51-59

YIN Shufei, LI Tian, ZHU Xinyi. (2019). Episodic memory performance and underlying brain mechanisms in elderly with subjective memory decline. Advances in Psychological Science, 27(1), 51-59

1 前言

21世纪以来, 中国人口老龄化问题日益突出, 预计到2050年老年人口将超过4亿, 占总人口的30%.认知功能是老年人保持独立的生活能力以及提升生活质量的重要基础.随着年龄增长, 老年人的许多心理功能特别是认知功能出现衰退, 这也是正常老化的必然过程.然而, 与正常的认知功能衰退不同, 有部分老年人会出现快速且持续性的认知能力下降, 最终发展成为老年性痴呆(Alzheimer’s Disease, AD) (Burns & Iliffe, 2009).AD是一种神经退行性疾病, 其发生是一个连续的病理生理过程, 并且这个过程在AD病人未表现出认知障碍的时期就已经开始发生.在相对较长的一段时间之后, 部分病人才会表现出轻度的认知障碍(mild cognitive impairment, MCI).直到AD后期, 病人神经元开始大量凋亡, 随之发生的认知损伤也将不再可逆.AD病理发展的这一特点使得人们对该疾病的早期识别和干预陷入困境.然而, 近年来, 主观记忆减退(subjective memory decline, SMD)概念的出现为这一困难的解决提供了新的契机.

主观记忆减退是指部分老年人会自我报告记忆力下降, 但在客观认知测验上的成绩仍处于正常范围之内(Jessen et al., 2014).有研究表明, SMD老年人情节记忆等认知功能下降的速率快于健康对照组, 罹患AD的风险更高(Buckley et al., 2016; Fonseca et al., 2015; Hueluer, Hertzog, Pearman, & Gerstorf, 2015); 并且他们在外在记忆行为尚未出现损伤的情况下, 其大脑的记忆相关脑区的神经活动已经出现异常(Erk et al., 2011).这些发现引起了认知老化及痴呆领域研究者的广泛兴趣.Jessen等人(2014)发表在《Alzheimers & Dementia》杂志上的文章初步确立了主观记忆减退研究的理论框架.为了强调对主观记忆减退进行深入研究的意义, 《Journal of Alzheimers Disease》杂志更是于2015年专题报道了主观记忆减退期的研究进展, 指出主观记忆减退期是AD自然发病过程的最初始阶段(Rabin et al., 2015; Reisberg & Gauthier, 2008).

因此, 探究主观记忆减退的记忆神经环路关键节点和路径的异常, 对深入理解老年痴呆的发病机制有极为重要的科学指导意义.同时, 对SMD老年人记忆环路的深入探究, 也必将为揭示人类记忆的神经机制做出独特的贡献.

2 主观记忆减退是AD最早期症状

值得注意的是, SMD老年人将会以每年6.67%的速率发展为MCI; 而大约50%的MCI病人在5年内会发展成为AD (Gauthier et al., 2006); 与没有SMD的老年人相比, SMD老年人罹患MCI或AD的风险要高出4.5~6.5倍(Jessen et al., 2010; Reisberg, Shulman, Torossian, Leng, & Zhu, 2010).因而, SMD老年人是罹患老年性痴呆的高风险人群.

越来越多的影像学证据显示, 虽然目前SMD老年人在行为测验上的成绩还没表现出明显下降, 但是其大脑可能已经发生了病理性改变(Contreras et al., 2017; 韩璎 等, 2015).与正常对照组老年人相比, SMD老年人β样淀粉沉积(Perrotin et al., 2017)和τ蛋白指标异常(Colijn & Grossberg, 2015; Garcia-Ptacek et al., 2016; Snitz et al., 2015a), 全脑灰质(Hafkemeijer et al., 2013)和海马的体积减小(Scheef et al., 2012; Stewart et al., 2011),左侧内嗅皮层厚度降低(Meiberth et al., 2015).而且, 基线的主观记忆损伤能预测接下来的情节记忆相关脑区(海马)的萎缩(Stewart et al., 2011).最近, Ferreira等人(2017)通过综合临床诊断,认知测验,脑成像和基因相关数据提出了一种测量SMD严重程度的方法; 该研究也主张SMD作为健康和MCI的中间状态能够为AD的早期诊断提供重要依据.这些证据支持了主观记忆减退是AD最早期症状的观点, 同时也提示对主观记忆减退进行深入研究对于痴呆早期识别和干预的重要意义.

3 主观记忆减退老年人的情节记忆

情节记忆是与人们日常生活关系最密切,发展最高级,成熟最晚的记忆系统, 受到了研究者的大量关注.主观报告情节记忆下降是SMD老年人的最典型表现.有研究发现SMD老年人在外在记忆行为尚未出现损伤的情况下, 其大脑的记忆相关脑区的神经活动已经出现异常(Erk et al., 2011).

3.1 SMD老年人情节记忆的行为表现

情节记忆是人类发展最高级,成熟最晚的外显记忆, 且受生理老化影响最大, 因而备受认知老化领域和认知神经科学领域的关注(Tulving, 1995).根据“多重记忆系统”, 情节记忆是个体对特定时间,特定地点所经历的特定事件的记忆, 将各种特定细节绑定(binding)在一起是其核心特征(Sherry & Schacter, 1987).而联结记忆(associative memory)即是在传统的内容记忆基础上发展而成的一种直接考察绑定的情节记忆形式(Horn, Kennedy, & Rodrigu, 2018).

伴随着年龄增长, 情节记忆成绩会表现出下降趋势(Mitchell, Johnson, Raye, & D’Esposito, 2000; Old & Naveh-Benjamin, 2008).根据联结缺陷假说(Associative Deficit Hypothesis, Naveh- Benjamin, 2000), 老年人情节记忆下降的原因就在于老年人在产生和提取项目之间的联结能力存在缺陷.联结记忆能力下降不仅是正常老化的显著表现, 也是老年痴呆患者最早出现的认知障碍, 因此AD 也被称为“失连接综合征”.

主观报告情节记忆下降, 特别是需要将两个信息绑定的联结记忆存在问题, 是SMD老年人最典型的表现, 比如SMD老年人会抱怨自己经常忘记物体的摆放位置或不能回忆起某个好朋友的名字等(Lam, Lui, Tam, & Chiu, 2010).多个横向和纵向研究证据显示, 主观记忆成绩与客观认知状况显著相关(Amariglio, Townsend, Grodstein, Sperling, & Rentz, 2011; Cosentino, Devanand, & Gurland, 2018; Hülür, Willis, Hertzog, Schaie, & Gerstorf, 2018; Carrasco et al., 2017; Seo, Kim, Choi, Lee, & Choo, 2017); 而且, 虽然SMD老年人在情节记忆等认知测验上的成绩与健康对照组老年人没有显著差异, 但与健康对照组老年人相比, SMD老年人未来在情节记忆等认知功能上下降的速率更快, 罹患AD的风险更高(Fonseca et al., 2015; Hueluer et al., 2015; Horn et al., 2018; Rönnlund, Sundström, Adolfsson, & Nilsson, 2015; Scheef et al., 2012).比如, Koppara等人(2015)通过追踪调查比较了SMD老年人(N = 1337)和健康对照组老年人(N = 993)在8年间认知成绩的变化轨迹, 发现SMD老年人在即时和延时回忆任务上成绩下降的速率均要显著快于健康对照组老年人.最近的研究也表明, SMD能够预测老年人在单词配对和名字/面容配对任务中的表现(Horn et al., 2018); SMD老年人表现出更弱的情节记忆练习效应(practice effects, 即通过反复的练习, 测验成绩会相应提高), 在心理运动速度和语言的表现上也更差, 并且有更高比例发展为MCI和AD (Kielb, Rogalski, Weintraub, & Rademaker, 2017).

另外, 有证据显示, 情节记忆训练能够对SMD老年人的记忆状况有一定的改善作用(Boa et al., 2018; Cohen-Mansfield et al., 2015); 最近关于认知训练对SMD老年人认知状况提升效果的元分析研究也支持了这一结果(Smart et al., 2017), 说明SMD老年人的情节记忆具有一定的可塑性.然而, 也有研究发现, 相对于正常老年人来说, 情节记忆训练对SMD老年人的作用更小(Engvig et al., 2014; Pike, Amina, Ben, Sarah, & Kinsella, 2015).比如, Engvig等(2014)针对SMD和健康对照组老年人开展了情节记忆训练, 来考察SMD老年人脑功能的可塑性.结果发现, 经过8周的情节记忆训练, (1) SMD老年人和健康对照组老年人在情节记忆相关脑区的灰质体积上表现出相同程度的提高; (2) SMD老年人的海马区域体积在个体水平上的变化与更好的情节记忆成绩相关, 但是仅健康对照组老年人在海马区域体积有显著增加, SMD则没有.Pike等人(2015)通过口头配对任务(verbal paired associate learning task)对SMD老年人的记忆训练效果作出了评估.结果发现, 虽然SMD老年人和健康组老年人的任务成绩都有了显著提升, 但是健康组老年人的提升效果比SMD老年人的更好.因此, 虽然与健康对照组老年人相比, SMD老年人在客观认知测验上的表现没有显著下降, 但SMD老年人主观报告的记忆力更差, 在未来几年内其情节记忆能力下降的速率会更快, 从情节记忆训练中的获益会更小.

3.2 SMD老年人情节记忆加工的脑机制

情节记忆主要依赖于内侧颞叶(medial temporal lobe)系统(包括海马,海马旁回和内嗅皮层等脑区)以及前额叶,梭状回和后内侧顶叶等区域) (Simons & Spiers, 2003).海马是记忆功能的核心脑区(Eichenbaum & Fortin, 2003; Moscovitch, Cabeza, Winocur, & Nadel, 2016), 海马的绑定能力降低是情节记忆受损的内在机制(Mitchell et al., 2000).除了海马的参与外, 情节记忆同样依赖前额叶的激活(Fletcher, Shallice, & Dolan, 1998; Lepage, Ghaffar, Nyberg, & Tulving, 2000; Umeda et al., 2005).

虽然AD的病因和发病机制尚未明晰, 但其主要的神经病理特征为β样淀粉蛋白(Amyloid-β, Aβ)沉淀形成的细胞外老年斑和τ蛋白过度磷酸化形成的神经细胞神经原纤维缠结, 以及神经元丢失伴胶质细胞增生等(Hashimoto, Rockenstein, Crews, & Masliah, 2003; Hernández & Avila, 2007).随着SMD概念的出现, 研究者也开始将关注点放到SMD老年人记忆相关脑区的Aβ和τ蛋白相关指标的变化上.众多PET研究表明, 在认知测验表现正常的老年人中, 主观报告记忆减退越严重的老人, 其Aβ与τ蛋白沉积负担越高 (Amariglio et al., 2012, 2015; Perrotin, Mormino, Madison, Hayenga, & Jagust, 2012; Horn et al., 2018; Rowe et al., 2010; Snitz et al., 2015b; Swinford, Risacher, Charil, Schwarz, & Saykin, 2018).根据一项长达5年的追踪研究, 在55名SMD和94名MCI被试中, 72.4%被试(83%MCI和27%SCD)的Aβ与τ蛋白相关指标达到AD的标准, 这说明相对于正常老年人, 无论是SMD还是MCI老年人发展成为AD的风险更高(Sierra-rio et al., 2015).Buckley等(2016)等人更是通过纵向追踪数据表明, 相对于低Aβ蛋白沉积负担的低主观报告记忆减退的老年人, 高Aβ蛋白沉积负担的高主观报告记忆减退老年人的海马体积更小, 同时发展成为MCI和AD的几率更高.最近的一项研究也表明, 更多的SMD与内嗅皮层中越严重的τ和Aβ蛋白沉积负担相关(Buckley et al., 2017).

随着AD病程的发展, 大脑神经代谢产物的异常有可能导致结构上的变化.目前, 通过对大脑体积,皮层厚度和皮层表面等形态学上的测量, 研究者们也对SMD老年人的大脑结构上的变化进行了探查.大部分研究发现, SMD老年人在多个不同的脑区出现体积萎缩, 主要集中在内侧颞叶系统, 包括海马,海马旁回和内嗅皮层等脑区(Park et al., 2018; Striepens et al., 2010; Vannini et al., 2017).Jessen等人(2006)通过将AD患者,MCI和SMD老年人与正常老年人(NC)的海马和内嗅皮层的体积进行比较发现, 随着病程的发展, 内嗅皮层的体积逐渐减小(即NC > SMD > MCI > AD).虽然左侧海马体积的减小未达到显著水平, 但是仍然保持着逐渐减小的趋势.后来的研究也发现了相似的结果:Scheef等人(2012)发现SMD老年人的右侧海马体积要比正常老年人的小; 同样, Ryu等人(2017)结合MRI和DTI技术也发现, 相对于正常老年人来说, SMD老年人的内嗅皮层体积更低, 海马的白质结构也出现显著变化.当然, 也有少部分研究并没有发现SMD老年人和正常老年人在大脑结构上的显著差异(Tepest et al., 2008; Sluimer et al., 2008), 但是这些结果仍然提示SMD老年人的大脑结构表现出变化的趋势.一方面, 出现这些结果的原因可能是不同的研究采用的方法不同, 包括使用的成像技术,比较方法,测量指标上的差异; 另一方面, SMD老年人在AD病程发展中的个体差异可能为不一致的结果作出解释.

在SMD阶段, 大脑在结构上已经表现出一定变化, 那么大脑在功能上是否出现异常呢?通过任务态fMRI技术, 大量研究发现SMD老年人在情节记忆任务下的激活模式与健康对照组老人存在差异, 主要表现为SMD老人在记忆加工的不同阶段都可能表现出额外的激活增强; 但组间差异是否在某些加工阶段出现, 不同研究的结果存在差异(Erk et al., 2011; Hayes et al., 2017; Rami et al., 2012; Rodda, Dannhauser, Cutinha, Shergill, & Walker, 2009).比如, Rami等(2012)通过视觉记忆编码任务发现, 与健康对照组老年人相比, SMD老年人在编码期间楔前叶和后扣带皮层的激活更强.Rodda等人(2009)发现在情节记忆编码任务下, 虽然SMD老人和健康对照组老人都激活了左侧前额叶和小脑, 但主观记忆减退老人还额外激活了左内侧颞叶,顶枕皮层和内侧额叶, 而且SMD老人在左侧前额叶的激活增强与其在记忆任务上的成绩显著相关; 类似的, Erk等人(2011)也发现, 与健康组老年人相比, SMD老年人在情节记忆回忆(recall)过程中右侧海马活动减弱, 与此同时右侧背外侧前额叶激活增强, 这些结果提示了海马和前额叶等区域活动的功能性改变可能作为一种补偿机制促进了SMD老年人记忆成绩的保持.不过, 在该研究中, 两组老年人在编码和再认过程中脑激活模式没有显著差异.最近, Hayes等人(2017)通过比较SMD老年人(n = 23)和健康对照组老年人(n = 41)在相继记忆效应(subsequent memory effects, 即在编码任务中击中项目的激活比遗忘项目的激活更强)上的差异来考察SMD老年人在记忆编码加工中的脑激活.结果发现, 与对照组老年人相比, SMD老年人在枕叶,顶上小叶和后扣带回表现出更低的相继记忆效应; 而且在默认网络相关脑区(包括后扣带回,楔前叶和腹内侧前额叶)表现出更强的负性相继记忆效应.这一结果提示, SMD老年人编码成功要依赖于独特的神经机制, 这可能反映了其任务指向性注意的整体下降.因此, SMD老年人情节记忆的回忆过程可能与海马和前额叶活动的功能性改变有关; 而编码和再认等加工过程的神经机制尚且需要未来进一步研究探索.

4 研究小结与展望

4.1 小结

综上所述, 主观记忆减退期是AD自然发病过程的最初始阶段, 也是AD早期识别和干预最有效的阶段(Rabin et al., 2015; Reisberg & Gauthier, 2008; 尹述飞, 朱心怡, 李娟, 2016).主观报告情节记忆下降是SMD老年人的最典型表现.虽然SMD老年人在外在记忆行为尚未出现损伤的情况下, 其大脑记忆相关脑区的神经活动已经出现异常, 但目前关于SMD老年人情节记忆加工的脑机制尚不明确.

第一, 与正常老年人相比, SMD老年人在情节记忆上主要表现为自我报告的主观记忆成绩更差, 而主观记忆成绩与客观记忆测验成绩呈正相关; SMD老年人同时也表现出更弱的情节记忆练习效应和相继记忆效应; 在未来几年内记忆测验上的行为成绩下降速率更快, 并且有更高的比例发展为MCI和AD.

第二, 关于正常老年人和MCI/AD的研究提示前额叶和海马之间的功能性连接是情节记忆(特别是联结记忆)的神经环路.尽管有证据提示SMD老年人在情节记忆任务下发生了脑功能性补偿(前额叶激活增强和海马激活减弱), 但并未从功能整合的角度(前额叶-海马之间功能连接)去探讨其情节记忆加工的脑机制.如果采用任务下的激活脑区作为目标脑区, 先考察任务下的功能连接, 然后进一步验证这一功能连接是否在静息状态下仍然存在, 将能更直接客观地揭示SMD老年人情节记忆损伤的神经通路.因此, 未来研究可以进一步探索SMD老年人的情节记忆表现是否与其海马与前额叶之间的功能连接异常存在显著关联.

第三, 前人研究提示SMD老年人海马和前额叶等脑区活动异常主要影响情节记忆的提取过程(Erk et al., 2011).目前关于SMD老年人情节记忆编码等加工过程的研究结果还存在争议, 有研究认为SMD老年人在情节记忆编码过程中楔前叶和后扣带皮层的激活异常(Rami et al., 2012), 也有研究发现SMD老年人在情节记忆编码过程中的脑激活模式与健康组老年人没有差异(Erk et al., 2011).未来研究需要在收集SMD老年人在情节记忆编码,存储和提取等各加工阶段的影像学数据的基础上, 进一步深入分析其情节记忆加工过程的脑激活模式及功能连接模式的改变, 以便更深入地理解其情节记忆加工的脑机制.

4.2 研究展望

近年来, 研究者们不仅采用脑成像技术关注与退行性记忆损伤相关的脑激活异常, 也开始关注与这种损伤有关的脑区功能连接(functional connectivity)异常.功能连接技术是考察当活体在静息或进行任务操作时脑区之间的协同活动, 能够测量和比较不同脑区的神经生理活动之间的时间序列相关(Friston, Frith, & Frackowiak, 1993).对于退行性记忆损伤个体来说, 生理老化和病理性老化的双重影响会导致前额叶和海马均出现功能异常.这种功能异常可能体现在其本身的功能出现障碍, 更可能体现在与其他脑区之间的功能连接上, 特别是这二者之间的功能连接.

然而对介于正常老化和MCI患者之间的SMD老年人的脑区功能性连接的研究却非常缺乏.Hafkemeijer等人(2013)通过静息态影像数据的分析, 发现SMD老年人在默认网络(default mode network), 包括海马等区域的功能连接相对正常对照组老年人更强.而另一项静息态影像数据显示, 相比健康老年人, SMD老年人背内侧前额叶网络与右侧海马之间的功能连接水平显著下降(Hu, Harzem, Huang, Weber, & Jessen, 2016), 该研究提示这可能与SMD老年人情节记忆系统损伤有关.Contreras等人(2017)通过考察SMD,MCI和AD老人在静息态下脑功能连接模式发现, 被试在情节记忆任务上的成绩与额顶网络-默认网络功能连接强度呈正相关.

遗憾的是, 关于SMD老年人在情节记忆加工过程中脑区功能性连接的研究几近真空地带.目前已有研究尝试利用这种技术探讨与AD/MCI有关的脑区功能连接异常(Grady, Bernstein, Beig, & Siegenthaler, 2002; Greg et al., 2007; Wang et al., 2006).比如Grady等(2002)发现, 在面孔记忆任务中AD患者海马与前额叶皮层的功能性连接丧失.MCI在情节记忆提取任务中, 海马与前额叶等脑区的功能性连接减弱(Hampstead, Khoshnoodi, Yan, Deshpande, & Sathian, 2016), 而与更弥散区域的连接加强, 以补偿上述连接的减弱(Bai et al., 2009).这些结果支持了海马与前额叶功能性连接在退行性记忆损伤病人中受损的假设.

SMD老年人之所以在记忆相关的行为测验成绩上没有表现出明显下降, 很可能的原因在于他们更容易发生脑活动的功能性补偿(Jessen et al., 2014).Erk等人(2011)的研究虽然采用面孔-职业绑定的情节记忆任务初步发现了SMD老年人的神经性补偿机制, 但是该研究仅从前额叶和海马的激活变化的角度进行分析.而SMD老年人情节记忆损伤既可能与前额叶和海马自身功能相关, 也可能与这两个区域之间的功能连接有关.而且, 该研究在工作记忆任务下没有发现相应的补偿, 这也提示在情节记忆任务下去考察SMD老年人的脑区功能连接, 对于阐明情节记忆加工的脑机制及痴呆的早期识别意义重大.如果采用任务下的激活脑区作为目标脑区, 先考察任务下的功能连接, 然后进一步验证这一功能连接是否在静息状态下仍然存在, 将能更直接客观地揭示SMD老年人联结记忆损伤的神经通路机制.

主观记忆减退是老年痴呆的最初始阶段, 而SMD老年人最典型的表现就是主观报告情节记忆下降.探究主观记忆减退的记忆神经环路关键节点和路径的异常, 揭示神经环路在老年痴呆发生发展中的变化规律, 对深入理解老年痴呆的发病机制, 早期识别,并提供合适有效的干预方案, 从而降低老年痴呆的发病率,延缓老年痴呆发展的进程, 有及其重要的科学指导意义.同时, SMD老年人作为特殊的记忆损伤群体, 对其神经环路的深入探究, 也必将为揭示人类记忆的神经机制做出独特的贡献.

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Jama Neurology, 74(12), 1455-1463.

URL     PMID:28973551      [本文引用: 1]

The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β65=650.35; 95% CI, 0.19-.52; P65<65.001) and Aβ burden (β65=650.24; 95% CI, 0.08-.40; P65=65.005), but not inferior temporal tau burden (β65=650.10; 95% CI, -0.08 to 0.28; P65=65.27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β65=650.36; 95% CI, 0.15-.58; P65=65.001), and no interaction influenced SCD (β65=65-0.36; 95% CI, -0.34 to 0.09; P65=65.25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.

Buckley R. F., Maruff P., Ames D., Bourgeat P., Martins R. N., Masters C. L ., et al. Study, A. (2016).

Subjective memory decline predicts greater rates of clinical progression in preclinical Alzheimer's disease.

Alzheimer’s & Dementia, 12(7), 796-804.

URL     PMID:26852195      [本文引用: 1]

The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high β-amyloid burden (CN Aβ+). Fifty-eight CN Aβ+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed. In CN Aβ+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio02=025.1; 95% confidence interval, 1.4–20.0,P=02.02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume. High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Aβ+, more sensitive measures may be required to detect early subtle cognitive change.

Burns A., & Iliffe S. (2009).

Alzheimer's disease.

British Medical Journal, 338(7692), 158.

[本文引用: 1]

Carrasco P. M., Montenegro-Peña M., López-Higes R., Estrada E., Crespo D. P., & Rubio C. M ., et al. Azorín, D. G. (2017).

Subjective memory complaints in healthy older adults: Fewer complaints associated with depression and perceived health, more complaints also associated with lower memory performance.

Archives of Gerontology and Geriatrics, 70, 28-37.

URL     PMID:28039781      [本文引用: 1]

Abstract OBJECTIVES: (i) To analyze if general cognitive performance, perceived health and depression are predictors of Subjective Memory Complaints (SMC) contrasting their effect sizes; (ii) to analyze the relationship between SMC and objective memory by comparing a test that measures memory in daily life and a classical test of associated pairs; (iii) to examine if different subgroups, formed according to the MFE score, might have different behaviors regarding the studied variables. METHODS: Sample: 3921 community-dwelling people (mean age 70.41卤4.70) without cognitive impairment. Consecutive non-probabilistic recruitment. ASSESSMENT: Mini Cognitive Exam (MCE), daily memory Rivermead Behavioural Memory Test (RBMT), Paired Associates Learning (PAL), Geriatric Depression Scale (GDS), Nottingham Health Profile (NHP). Dependent variable: Memory Failures Everyday Questionnaire (MFE). RESULTS: Two different dimensions to explain SMC were found: One subjective (MFE, GDS, NHP) and other objective (RBMT, PAL, MCE), the first more strongly associated with SMC. SMC predictors were NHP, GDS, RBMT and PAL, in this order according to effect size. Considering MFE scores we subdivided the sample into three groups (low, medium, higher scores): low MFE group was associated with GDS; medium, with GDS, NPH and RBMT, and higher, with age as well. Effect size for every variable tended to grow as the MFE score was higher. CONCLUSION: SMC were associated with both health profile and depressive symptoms and, in a lesser degree, with memory and overall cognitive performance. In people with fewer SMC, these are only associated with depressive symptomatology. More SMC are associated with depression, poor health perception and lower memory. Copyright 2016 Elsevier Ireland Ltd. All rights reserved.

Cohen-Mansfield J., Cohen R., Buettner L., Eyal N., Jakobovits H., Rebok G ., et al. Sternberg, S. (2015).

Interventions for older persons reporting memory difficulties: A randomized controlled pilot study.

International Journal of Geriatric Psychiatry, 30(5), 478-486.

URL     PMID:25043482      [本文引用: 1]

The objective of this study is to compare three different interventions for persons who report memory difficulties: health promotion, cognitive training, and a participation-centered course, using a single-blind, randomized controlled design.Participants were 44 Israeli adults with memory complaints, aged 65 years or older. The main outcome variable was the Global Cognitive Score assessed using the MindStreams(庐) mild cognitive impairment assessment, a computerized cognitive assessment. The Mini-Mental State Examination and the self-report of memory difficulties were also utilized. To assess well-being, the UCLA Loneliness Scale-8 was used. Health was evaluated by self-report instruments.All three interventions resulted in significant improvement in cognitive function as measured by the computerized cognitive assessment. All approaches seemed to decrease loneliness. The only variable which showed a significant difference among the groups is the self-report of memory difficulties, in which the cognitive training group participants reported greater improvement than the other groups.Multiple approaches should be offered to older persons with memory complaints. The availability of diverse options would help fit the needs of a heterogeneous population. An educational media effort to promote the public's understanding of the efficacy of these multiple approaches is needed.

Colijn M.A., &Grossberg G.T . (2015).

Amyloid and tau biomarkers in subjective cognitive impairment.

Journal of Alzheimer’s Disease, 47(1), 1-8.

URL     [本文引用: 1]

Subjective (SCI) refers to concerns regarding one's cognitive functioning in the absence of objective evidence of impairment, and may represent an early stage of . However, as not all individuals with SCI cognitively decline, there is growing interest in the early identification of those individuals with SCI who are most at risk of developing . One promising method of early identification involves the use of biomarkers that are known to be associated with the pathophysiology of the disease; in particular, markers of amyloid and tau accumulation. While there has been substantial research on amyloid and tau biomarkers in the context of (), only recently has attention shifted to SCI, which may represent an even earlier stage in the disease course. The purpose of this paper is to qualitatively review the literature on amyloid and tau biomarkers in SCI. A brief discussion of non-amyloid/tau biomarkers is also included. Not surprisingly, we found that amyloid and tau biomarker profiles become increasingly abnormal from SCI, to , to . Additionally, although amyloid and tau biomarkers appear to be unable to differentiate between SCI and healthy controls, there is some evidence to suggest that they may be able to differentiate between those individuals with SCI who cognitively decline over time and those who do not. While this finding has potential clinical implications, achieving optimal predictive value will likely require further research into the use of numerous biomarkers in combination.

Contreras J. A., Goñi J., Risacher S. L., Amico E., Yoder K., Dzemidzic M ., et al. Saykin, A. J. (2017).

Cognitive complaints in older adults at risk for Alzheimer's disease are associated with altered resting-state networks.

Alzheimers & Dementia: Diagnosis, Assessment & Disease Monitoring, 6, 40-49.

URL     PMID:5266473      [本文引用: 1]

Pathophysiological changes that accompany early clinical symptoms in prodromal Alzheimer's disease (AD) may have a disruptive influence on brain networks. We investigated resting-state functional magnetic resonance imaging (rsfMRI), combined with brain connectomics, to assess changes in whole-brain functional connectivity (FC) in relation to neurocognitive variables. Participants included 58 older adults who underwent rsfMRI. Individual FC matrices were computed based on a 278-region parcellation. FastICA decomposition was performed on a matrix combining all subjects' FC. Each FC pattern was then used as a response in a multilinear regression model including neurocognitive variables associated with AD (cognitive complaint index [CCI] scores from self and informant, an episodic memory score, and an executive function score). Three connectivity independent component analysis (connICA) components (RSN, VIS, and FP-DMN FC patterns) associated with neurocognitive variables were identified based on prespecified criteria. RSN-pattern, characterized by increased FC within all resting-state networks, was negatively associated with self CCI. VIS-pattern, characterized by an increase in visual resting-state network, was negatively associated with CCI self or informant scores. FP-DMN-pattern, characterized by an increased interaction of frontoparietal and default mode networks (DMN), was positively associated with verbal episodic memory. Specific patterns of FC were differently associated with neurocognitive variables thought to change early in the course of AD. An integrative connectomics approach relating cognition to changes in FC may help identify preclinical and early prodromal stages of AD and help elucidate the complex relationship between subjective and objective indices of cognitive decline and differences in brain functional organization.

Cosentino S., Devanand D., & Gurland B . (2018).

A link between subjective perceptions of memory and physical function: Implications for subjective cognitive decline.

Journal of Alzheimer’s Disease, 61(4), 1387-1398.

URL     PMID:29376850      [本文引用: 1]

Background: Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Methods: Cognitively normal elderly participants of the German Study on Ageing, Cognition, and... [Show full abstract]

Eichenbaum H., & Fortin N. (2003).

Episodic memory and the hippocampus.

Current Directions in Psychological Science, 12(2), 53-57.

URL     [本文引用: 1]

What did you have for breakfast yesterday? Who went with you to the movies? Who did you see at work today? It is likely that you can answer all questions of this sort. Moreover, if you continue to focus on retrieving information relevant to one or more of these questions, you will recover an amazing amount of contextual detail that surrounded the personal experience. Now answer another question: Did you intend to remember any of these experiences? The likely answer in most cases will be no. Thus, this small exercise reveals that your brain contains a memory system that automatically captures the content of your daily life and stores it in a manner that permits you to intentionally retrieve and replay it.

Engvig A., Fjell A. M., Westlye L. T., Skaane N. V., Dale A. M., Holland D ., et al. Kristine, W. (2014).

Effects of cognitive training on gray matter volumes in memory clinic patients with subjective memory impairment.

Journal of Alzheimer’s Disease, 41(3), 779-791.

URL     PMID:24685630      [本文引用: 1]

Abstract Subjective memory impairment (SMI) is a common risk factor for Alzheimer's disease, with few established options for treatment. Here we investigate the effects of two months episodic memory training on regional brain atrophy in 19 memory clinic patients with SMI. We used a sensitive longitudinal magnetic resonance imaging protocol and compared the patients with 42 matched healthy volunteers randomly assigned to a group performing the same training, or a no-training control group. Following intervention, the SMI sample exhibited structural gray matter volume increases in brain regions encompassing the episodic memory network, with cortical volume expansion of comparable extent as healthy training participants. Further, we found significant hippocampal volume increases in the healthy training group but not in the SMI group. Still, individual differences in left hippocampal volume change in the patient group were related to verbal recall improvement following training. The present results reinforce earlier studies indicating intact brain plasticity in aging, and further suggest that training-related brain changes can be evident also in the earliest form of cognitive impairment.

Erk S., Spottke A., Meisen A., Wagner M., Walter H., & Jessen F . (2011).

Evidence of neuronal compensation during episodic memory in subjective memory impairment.

Archives of General Psychiatry, 68(8), 845-852.

URL     PMID:21810648      [本文引用: 5]

Accumulating evidence suggests that the mere subjective feeling of memory impairment in the absence of objective cognitive deficits may precede mild cognitive impairment in the continuum of Alzheimer disease manifestation. Brain imaging studies have provided insights into structural and functional alterations at the clinical stages of dementia and mild cognitive impairment, but the functional characteristics of subjective memory impairment (SMI) are largely unstudied.

Ferreira D., Falahati F., Linden C., Buckley R. F., Ellis K. A., Savage G ., et al. Westman, E. (2017).

A 'disease severity index' to identify individuals with subjective memory decline who will progress to mild cognitive impairment or dementia.

Scientific Reports, 7, 44368.

URL     PMID:5347012     

Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer’s disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions.

Fletcher P. C., Shallice T., & Dolan R. J . (1998).

The functional roles of prefrontal cortex in episodic memory.

Brain, 121(7), 1239-1248.

URL     PMID:9679776      [本文引用: 1]

Functional neuroimaging studies of retrieval show consistent activation of the right prefrontal and superior parietal cortex. We examined the specific role of the prefrontal cortex during retrieval with the hypothesis that this region mediates monitoring processes necessary for optimal recall. During functional neuroimaging with PET, subjects retrieved verbal material under two conditions. In the first, an organizational structure had been provided, prior to scanning, and this formed the basis for a monitored search while the scan took place. A comparison condition did not require a monitored search because recall was externally cued. In both conditions, when compared with baseline tasks prefrontal cortex and medial parietal activation was observed. Within the right prefrontal cortex activation an anatomical dissociation was seen between the dorsal and ventral prefrontal cortex. The dorsal region showed greater activation when monitoring demands were emphasized, while the ventral region showed greater activation when external cueing was emphasized. An unpredicted dissociation within the superior parietal activation was also observed, a dorsal region showing activation during the monitored search task and a more ventral region showing activation under the externally cued condition. The results provide evidence for functional specialization of the right prefrontal cortex for discrete cognitive processes during episodic retrieval.

Fonseca J. A. S., Ducksbury R., Rodda J., Whitfield T., Nagaraj C., Suresh K ., et al. Walker, Z. (2015).

Factors that predict cognitive decline in patients with subjective cognitive impairment.

International Psychogeriatrics, 27(10), 1671-1677.

URL     PMID:25812703      [本文引用: 2]

Current evidence supports the concept of a preclinical phase of Alzheimer's disease (AD) where pathological and imaging changes are present in asymptomatic individuals. Subjective cognitive impairment (SCI) may represent the earliest point on the continuum of AD. A better understanding of the baseline characteristics of this group of patients that later decline in cognition will enhance our knowledge of the very early disease processes, facilitate preventive strategies, early diagnosis, timely follow-up and treatment. An observational exploratory study which followed up 62 consecutive patients with SCI presenting to a memory clinic and compared baseline characteristics of SCI patients who declined cognitively with those who did not. Cognitive decline was defined as a progression to a diagnosis of amnestic mild cognitive impairment (aMCI) or dementia at follow-up. Patients were followed up for a mean of 44 months (range 12-112 months). At the time of follow up, 24% of patients had declined. Patients that declined were significantly older at onset of symptoms and first presentation to memory clinic, and took significantly more medications for physical illnesses. Patients that declined also performed significantly worse on Trail Making Test (TMT) B and Cambridge Cognitive Examination Revised (CAMCOG-R) at baseline. Survival analysis identified key variables that predicted decline (later age of onset and later age at first assessment). Patients who present with subjective memory complaints and are over the age of 61 years are at high risk of cognitive decline and warrant an in-depth assessment and follow-up.

Friston K. J., Frith C. D ., & Frackowiak, R. S. J. (1993).

Time-dependent changes in effective connectivity measured with PET.

Human Brain Mapping, 1(1), 69-79.

URL     [本文引用: 1]

A voxel-based method of measuring the effective connectivity between brain regions is presented. The approach is based on electrophysiological concepts and is applied to neurophysiological data obtained with (positron emission tomography (PET)) functional imaging. Time-dependent changes in effective connectivity were assessed during a verbal fluency activation paradigm using 12 consecutive measurements of regional cerebral blood flow (rCBF). The changes observed were predicted by an associative (Hebbian) model of plasticity, applied to cortical activity, measured in terms of rCBF. The main finding was, in most regions, a selective enhancement of effective connections from the distributed brain regions exhibiting the dominant pattern of correlated activity.

Garcia-Ptacek S., Eriksdotter M., Jelic V., Porta-Etessam J., Kåreholt I., & Manzano Palomo S . (2016).

Subjective cognitive impairment: Towards early identification of Alzheimer disease.

Neurología (English Edition), 31(8), 562-571.

URL     PMID:23601758      [本文引用: 1]

Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies. Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (A42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD.

Gauthier S., Reisberg B., Zaudig M., Petersen R. C., Ritchie K., Broich K ., et al. Winblad, B. (2006).

Mild cognitive impairment.

The Lancet, 367(9518), 1262-1270.

[本文引用: 1]

Grady C. L., Bernstein L. J., Beig S., & Siegenthaler A. L . (2002).

The effects of encoding task on age-related differences in the functional neuroanatomy of face memory.

Psychology and Aging, 17(1), 7-23.

URL     PMID:11931288      [本文引用: 1]

Abstract Age-related differences in brain activity mediating face recognition were examined using positron emission tomography. Participants encoded faces using a pleasant-unpleasant judgment, a right-left orientation task, and intentional learning. Scans also were obtained during recognition. Both young and old groups showed signficant effects of encoding task on recognition accuracy, but older adults showed reduced accuracy overall. Increased brain activity in older adults was similar to that seen in young adults during conditions associated with deeper processing, but was reduced during the shallow encoding and recognition conditions. Left prefrontal activity was less in older adults during encoding, but greater during recognition. Differential correlations of brain activity and behavior were found that suggest older adults use unique neural systems to facilitate face memory.

Greg A., Holly B., Roderick M. C., Hester A. L., Fields J. A., Weiner M. F ., et al. Cullum, C. M. (2007).

Reduced hippocampal functional connectivity in Alzheimer disease.

Archives of Neurology, 64(10), 1482-1487.

URL     PMID:17923631      [本文引用: 1]

ObjectiveTo determine if functional connectivity of the hippocampus is reduced in patients with Alzheimer disease.DesignFunctional connectivity magnetic resonance imaging was used to investigate coherence in the magnetic resonance signal between the hippocampus and all other regions of the brain.ParticipantsEight patients with probable Alzheimer disease and 8 healthy volunteers.ResultsControl subjects showed hippocampal functional connectivity with diffuse cortical, subcortical, and cerebellar sites, while patients demonstrated markedly reduced functional connectivity, including an absence of connectivity with the frontal lobes.ConclusionThese findings suggest a functional disconnection between the hippocampus and other brain regions in patients with Alzheimer disease.

Hafkemeijer A., Altmann-schneider I., Oleksik A. M., van de Wiel L., Middelkoop H. A. M ., & van Buchem, M. A., , et al. Rombouts, S. A. R. B. (2013).

Increased functional connectivity and brain atrophy in elderly with subjective memory complaints.

Brain Connectivity, 3(4), 353-362.

[本文引用: 1]

Hampstead B. M., Khoshnoodi M., Yan W., Deshpande G., & Sathian K . (2016).

Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults.

NeuroImage, 124(Pt A), 997-1008.

URL     PMID:26458520      [本文引用: 1]

Previous research has shown that there is considerable overlap in the neural networks mediating successful memory encoding and retrieval. However, little is known about how the relevant human brain regions interact during these distinct phases of memory or how such interactions are affected by memory deficits that characterize mild cognitive impairment (MCI), a condition that often precedes dementia due to Alzheimer's disease. Here we employed multivariate Granger causality analysis using autoregressive modeling of inferred neuronal time series obtained by deconvolving the hemodynamic response function from measured blood oxygenation level-dependent (BOLD) time series data, in order to examine the effective connectivity between brain regions during successful encoding and/or retrieval of object location associations in MCI patients and comparable healthy older adults. During encoding, healthy older adults demonstrated a left hemisphere dominant pattern where the inferior frontal junction, anterior intraparietal sulcus (likely involving the parietal eye fields), and posterior cingulate cortex drove activation in most left hemisphere regions and virtually every right hemisphere region tested. These regions are part of a frontoparietal network that mediates top-down cognitive control and is implicated in successful memory formation. In contrast, in the MCI patients, the right frontal eye field drove activation in every left hemisphere region examined, suggesting reliance on more basic visual search processes. Retrieval in the healthy older adults was primarily driven by the right hippocampus with lesser contributions of the right anterior thalamic nuclei and right inferior frontal sulcus, consistent with theoretical models holding the hippocampus as critical for the successful retrieval of memories. The pattern differed in MCI patients, in whom the right inferior frontal junction and right anterior thalamus drove successful memory retrieval, reflecting the characteristic hippocampal dysfunction of these patients. These findings demonstrate that neural network interactions differ markedly between MCI patients and healthy older adults. Future efforts will investigate the impact of cognitive rehabilitation of memory on these connectivity patterns.

Hashimoto M., Rockenstein E., Crews L., & Masliah E . (2003).

Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases.

Neuromolecular Medicine, 4(1-2), 21-35.

[本文引用: 1]

Hayes J. M., Tang L., Viviano R. P., van Rooden S., Ofen N., & Damoiseaux J. S . (2017).

Subjective memory complaints are associated with brain activation supporting successful memory encoding.

Neurobiology of Aging, 60(7), 71-80.

URL     PMID:28923533      [本文引用: 1]

react-text: 127 It is commonly assumed that functional brain connectivity reflects structural brain connectivity. The exact relationship between structure and function, however, might not be straightforward. In this review we aim to examine how our understanding of the relationship between structure and function in the 'resting' brain has advanced over the last several years. We discuss eight articles that... /react-text react-text: 128 /react-text [Show full abstract]

Hernández F., & Avila J. (2007).

Tauopathies.

Cellular and Molecular Life Sciences, 64(17), 2219-2233.

[本文引用: 1]

Horn M. M., Kennedy K. M., & Rodrigue K. M . (2018).

Association between subjective memory assessment and associative memory performance: Role of AD risk factors.

Psychology and Aging, 33(1), 109-118.

URL     PMID:29494182      [本文引用: 5]

Decline in associative memory abilities is a common cognitive complaint among older adults and is detectable in both normal aging and in prodromal Alzheimer’s disease (AD). Subjective memory (SM) complaints may serve as an earlier marker of these mnemonic changes; however, previous research examining the predictive utility of SM to observed memory performance yielded inconsistent results. This inconsistency is likely due to other sources of variance that occur with memory decline such as mood/depression issues, presence of apolipoprotein E (APOE ε4) genotype, or beta-amyloid deposition. Here we examine the relationship between SM and associative memory ability in the context of factors that increase susceptibility to AD in 195 healthy adults (79 men) aged 20–94 years. Participants completed an SM questionnaire, a mood/depression scale, two associative memory tests (a word-pair and a name-face test), and were genotyped for APOE ε4. PET-amyloid imaging data were collected for a subset of those over 50 years of age (N = 74). We found that SM predicted performance on both associative memory tests even after covarying for age, sex, mood, and APOE ε4 status. Interestingly, for the name-face associative task, increased SM concerns predicted memory performance selectively in participants over the age of 60, with the APOEε4 risk group showing the strongest effect. Finally, men with higher beta-amyloid deposition reported more memory complaints. Our findings suggest that SM reliably tracks memory performance, even in cognitively healthy adults, and may reflect an increased risk for AD. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Hu X., Harzem J., Huang B., Weber B., & Jessen F . (2016).

Abnormal functional connectivity within default mode network in persons with subjective cognitive decline: Self-reflection of own memory deficits?

Alzheimers & Dementia, 12(7), 39.

URL     [本文引用: 1]

Hueluer G., Hertzog C., Pearman A. M., & Gerstorf D . (2015).

Correlates and moderators of change in subjective memory and memory performance: Findings from the health and retirement study.

Gerontology, 61(3), 232-240.

URL     PMID:25790970      [本文引用: 2]

Abstract Aging researchers have long been interested in understanding individuals' subjective perceptions of their own memory functioning. Previous research has shown that subjective memory ratings are partly based on memory performance but also reflect the influence of other factors, such as depressive symptoms. The aim of the present study was to examine (1) longitudinal associations between trajectories of subjective memory and memory performance, (2) variables that predict levels of and changes in subjective memory and memory performance, and (3) variables that moderate associations between these constructs. We applied a latent growth curve model to four occasions of data from 15,824 participants of the Health and Retirement Study (HRS; mean age at baseline=64.27 years, SD=9.90; 58% women). Results revealed that latent changes in subjective memory were correlated with latent changes in memory performance (0.49), indicating that participants who reported steeper declines of subjective memory indeed showed steeper declines of memory performance over time. Three major patterns of associations emerged with respect to predictors of subjective memory and subjective memory change. First, the level of memory performance showed stronger associations with age, gender, and education, whereas subjective memory was more strongly associated with subjective age and personality traits. For example, women performed better than men on the episodic memory test, but there were no gender differences in subjective memory. Also, older age was associated with steeper declines of memory performance but with less decline of subjective memory. Second, personality traits that predicted subjective memory intercepts did not predict subjective memory slopes. Third, the strength of associations between levels and slopes of subjective memory and memory performance varied as a function of gender, education, depressive symptoms, and personality traits. Conscientiousness moderated the relationship of the level of subjective memory to the level of memory performance, consistent with the hypothesis that persons high in conscientiousness more accurately monitor memory successes and failures. The results reinforce the importance of depressive symptoms as a predictor of subjective memory but also indicate that a broader perspective on the reasons why memory complaints have modest correlations with memory itself is needed. 2015 S. Karger AG, Basel

Hülür G., Willis S. L., Hertzog C., Schaie K. W., & Gerstorf D . (2018).

Is subjective memory specific for memory performance or general across cognitive domains? Findings from the Seattle longitudinal study.

Psychology and Aging, 33(3), 448-460.

URL     PMID:29756802     

A growing body of research has examined whether people’s judgments of their own memory functioning accurately reflect their memory performance at cross-section and over time. Relatively less is known about whether these judgments are specifically based on memory performance, or reflect general cognitive change. The aim of the present study was to examine longitudinal associations of subjective memory with performance in tests of episodic memory and a wide range of other cognitive tests, including the Wechsler Adult Intelligence Scale—Revised (WAIS–R) Block Design, Comprehension, Digit Span, Digit Symbol, and Vocabulary subtests. We applied latent growth curve models to five occasions over up to 16 years of neuropsychological assessments from 956 participants of the Seattle Longitudinal Study (SLS; 57% women; age at baseline: M = 65.1, SD = 11.4, 38 – 96 years). Results revealed that lower self-reported Frequency of Forgetting was significantly associated with better performance in all cognitive domains at baseline. The baseline correlation of Frequency of Forgetting with memory performance was stronger than its correlations with performance in other cognitive tests. Furthermore, additional analyses with baseline data showed that a latent memory performance factor reliably predicted Frequency of Forgetting after controlling for a general cognitive factor. Over time, steeper increases in Frequency of Forgetting were associated with steeper declines in tests of memory performance and in the Block Design and Digit Symbol subtests. Taken together, these findings suggest that although self-reported Frequency of Forgetting reflects performance in a broad range of other cognitive domains, it also shows some specificity for memory performance. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Jessen F., Amariglio R. E., van Boxtel M., Breteler M., Ceccaldi M., & Chételat G ., et al. Wagner, M. (2014).

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease.

Alzheimers & Dementia, 10(6), 844-852.

URL     PMID:4317324      [本文引用: 2]

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCDplus.

Jessen F., Feyen L., Freymann K., Tepest R., Maier W., & Heun R ., et al. Scheef, L. (2006).

Volume reduction of the entorhinal cortex in subjective memory impairment.

Neurobiology of Aging, 27(12), 1751-1756.

URL     PMID:16309795     

To examine the biological basis of subjective memory impairment (SMI), defined as the feeling of memory worsening with normal memory performance, we measured the volume of the entorhinal cortex (EC) and the hippocampus in SMI subjects, patients with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) and healthy controls (CO). Compared with controls, the EC was smaller in the SMI group (left: p = 0.060; right: p = 0.045) and in the other two groups in the following order: CO > SMI > MCI > AD. The same sequence was observed with regard to hippocampal volumes, but the volume reduction of the left hippocampus in the SMI group only reached a trend towards significance ( p = 0.072) and the right was not significantly smaller compared with controls ( p = 0.37). Compared with controls the average (left/right) volume reduction of the EC was 18% (SMI), 26% (MCI) and 44% (AD). The mean volume reduction of the hippocampus was 6% (SMI), 16% (MCI) and 19% (AD). Our results mirror the temporal sequence of neurodegeneration in AD and support the concept of SMI as the first clinical manifestation of dementia.

Jessen F., Wiese B., Bachmann C., Eifflaender-Gorfer S., Haller F., Kölsch H ., et al. Rickel, H. (2010).

Prediction of dementia by subjective memory impairment: Effects of severity and temporal association with cognitive impairment.

Archives of General Psychiatry, 67(4), 414-422.

URL     PMID:20368517      [本文引用: 1]

Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. Longitudinal cohort study with follow-up examinations at 1(1/2) and 3 years after baseline. Primary care medical record registry sample. A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.

Kielb S., Rogalski E., Weintraub S., & Rademaker A . (2017).

Objective features of subjective cognitive decline in a United States national database.

Alzheimer’s & Dementia, 13(12), 1337-1344.

URL     PMID:28586648      [本文引用: 1]

Abstract INTRODUCTION: Functional and cognitive features of subjective cognitive decline (SCD) were identified in a longitudinal database from the National Alzheimer's Coordinating Center. METHODS: Cognitively normal older adults with (SCD+) and without (SCD-) self-reported memory complaints (N0002=00023915) were compared on (1) baseline Functional Assessment Questionnaire ratings, (2) baseline scores and longitudinal rate of change estimates from nine neuropsychological tests, and (3) final clinical diagnoses. RESULTS: SCD+0002had higher baseline ratings of functional impairment, reduced episodic memory practice effects and poorer performance on neuropsychological tests of psychomotor speed and language, and higher frequencies of mild cognitive impairment and dementia diagnoses at the end of follow-up compared with the SCD-group. DISCUSSION: Subtle clinical features of SCD identified in this large cohort are difficult to detect at the individual level. More sensitive tests are needed to identify those with SCD who are vulnerable to cognitive decline and dementia. Copyright 0008 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Koppara A., Wagner M., Lange C., Ernst A., Wiese B., & König H-H ., et al. Jessen, F. (2015).

Cognitive performance before and after the onset of subjective cognitive decline in old age.

Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 1(2), 194-205.

URL     PMID:27239504     

Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Cognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N = 2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. Baseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. SCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.

Lam L. C. W., Lui V. W. C., Tam C. W. C ., & Chiu, H. F. K. (2010).

Subjective memory complaints in Chinese subjects with mild cognitive impairment and early Alzheimer's disease.

International Journal of Geriatric Psychiatry, 20(9), 876-882.

URL     PMID:16116581      [本文引用: 1]

The findings suggested that a short memory questionnaire is useful in the screening of MCI, particularly in subjects who already present with subtle functioning disturbances. Subjective memory complaints were significant correlated with objective performance of memory functions, reflecting the usefulness of memory complaints in the assessment of MCI. Copyright 2005 John Wiley & Sons, Ltd.

Lepage M., Ghaffar O., Nyberg L., & Tulving E . (2000).

Prefrontal cortex and episodic memory retrieval mode.

Proceedings of the National Academy of Sciences of the United States of America, 97(1), 506-511.

URL     PMID:10618448      [本文引用: 1]

A multistudy analysis of positron emission tomography data identified three right prefrontal and two left prefrontal cortical sites, as well as a region in the anterior cingulate gyrus, where neuronal activity is correlated with the maintenance of episodic memory retrieval mode (REMO), a basic and necessary condition of remembering past experiences. The right prefrontal sites were near the frontal pole [Brodmann's area (BA) 10], frontal operculum (BA 47/45), and lateral dorsal area (BA 8/9). The two left prefrontal sites were homotopical with the right frontal pole and opercular sites. The same kinds of REMO sites were not observed in any other cerebral region. Many previous functional neuroimaging studies of episodic memory retrieval have reported activations near the frontal REMO sites identified here, although their function has not been clear. Many of these, too, probably have signaled their involvement in REMO. We propose that REMO activations largely if not entirely account for the frontal hemispheric asymmetry of retrieval as described by the original hemispheric encoding retrieval asymmetry model.

Meiberth D., Scheef L., Wolfsgruber S., Boecker H., Block W., Träber F ., et al. Jessen, F. (2015).

Cortical thinning in individuals with subjective memory impairment.

Journal of Alzheimer’s Disease, 45(1), 139-146.

URL     PMID:25471190      [本文引用: 1]

Elderly individuals with subjective impairment (SMI) report decline, but perform within the age-, gender-, and education- adjusted normal range on neuropsychological tests. Longitudinal studies indicate SMI as a risk factor or early sign of (AD). There is increasing evidence from neuroimaging that at the group level, subjects with SMI display evidence of AD related pathology. This study aimed to determine differences in cortical thickness between individuals with SMI and healthy control subjects (CO) using the FreeSurfer environment. 110 participants (41 SMI/69 CO) underwent structural 3D-T1 MR imaging. Cortical thickness values were compared between groups in predefined AD-related brain regions of the medial temporal lobe, namely the bilateral entorhinal cortex and bilateral parahippocampal cortex. Cortical thickness reduction was observed in the SMI group compared to controls in the left entorhinal cortex (p = 0.003). We interpret our findings as evidence of early AD-related brain changes in persons with SMI.

Mitchell K. J., Johnson M. K., Raye C. L., & D’Esposito M . (2000).

fMRI evidence of age-related hippocampal dysfunction in feature binding in working memory.

Cognitive Brain Research, 10(1-2), 197-206.

URL     PMID:10978709      [本文引用: 2]

Richly detailed memories for particular events depend on processes that bind individual features of experience together. Previous cognitive behavioral research indicates that older adults have more difficulty than young adults in conditions requiring feature binding. We used functional magnetic resonance imaging (fMRI) during a working memory task to identify neural substrates of this age-related deficit in feature binding. For young, but not older, adults there was greater activation in left anterior hippocampus on combination trials (remember objects together with their locations) than on trials in which participants were told to remember only which objects or only which locations occurred. The results provide neuroimaging evidence for an age-related hippocampal dysfunction in feature binding in working memory.

Moscovitch M., Cabeza R., Winocur G., & Nadel L . (2016).

Episodic memory and beyond: The hippocampus and neocortex in transformation.

Annual Review of Psychology, 67(1), 105-134.

[本文引用: 1]

Naveh-Benjamin M. . (2000).

Adult age differences in memory performance: Tests of an associative deficit hypothesis.

Journal of Experimental Psychology Learning Memory and Cognition, 26(5), 1170-1187.

URL     PMID:11009251      [本文引用: 1]

Abstract An associative hypothesis to explain and predict older adults' deficient explicit episodic memory performance was outlined and tested. The hypothesis attributes a substantial part of older adults' deficient memory performance to their difficulty in merging unrelated attributes-units of an episode into a cohesive unit. Although each of the components can be memorized to a reasonable degree, the associations that tie the attributes-units to each other grow weaker in old age. Four experiments are reported that provide (a) a converging validity to the hypothesis by demonstrating this associative deficit for both interitem relationships and intraitem relationships and (b) a discriminant validity to the hypothesis by contrasting and testing competing predictions made by the associative hypothesis and by alternative hypotheses. The implications of these results to older adults' episodic memory performance are discussed.

Old S.R., & Naveh-Benjamin M. (2008).

Memory for people and their actions: Further evidence for an age-related associative deficit.

Psychology and Aging, 23(2), 467-472.

URL     PMID:18573021      [本文引用: 1]

The associative deficit hypothesis (M. Naveh-Benjamin, 2000) attributes age-related memory deficits to the inability to encode and retrieve bound units of information. The present experiment extended this deficit to a new form of stimuli, dynamic displays of people and their performance of everyday actions. Older and younger adults viewed a series of brief video clips, each showing a different person performing a different action, and were tested over memory for individual people, individual actions, and the person-action combinations. Older adults did exhibit an associative deficit, and this was related to an increased proportion of false alarms on the associative test.

Park S., Ryu S. H., Yoo Y., Yang J. J., Kwon H., & Youn J. H ., et al. (2018).

Neural predictors of cognitive improvement by multi-strategic memory training based on metamemory in older adults with subjective memory complaints.

Scientific Reports, 8(1), 1095.

URL     PMID:29348440      [本文引用: 1]

Previous studies have indicated that memory training may help older people improve cognition. However, evidence regarding who will benefit from such memory trainings has not been fully discovered yet. Understanding the clinical and neural inter-individual differences for predicting cognitive improvement is important for maximizing the training efficacy of memory-training programs. The purpose of this study was to find the individual characteristics and brain morphological characteristics that predict cognitive improvement after a multi-strategic memory training based on metamemory concept. Among a total of 49 older adults, 39 participated in the memory-training program and 10 did not. All of them underwent brain MRIs at the entry of the training and received the neuropsychological tests twice, before and after the training. Stepwise regression analysis showed that lower years of education predicted cognitive improvement in the training group. In MRI, thinner cortices of precuneus, cuneus and posterior cingulate gyrus and higher white matter anisotropy of the splenium of corpus callosum predicted cognitive improvement in the training group. Old age, lower education level and individual differences in cortical thickness and white matter microstructure of the episodic memory network may predict outcomes following multi-strategic training.

Perrotin A., La Joie R., de La Sayette V., Barré L., Mézenge F., Mutlu J ., et al. Chételat, G. (2017).

Subjective cognitive decline in cognitively normal elders from the community or from a memory clinic: Differential affective and imaging correlates.

Alzheimer’s & Dementia, 13(5), 550-560.

URL     PMID:27693187      [本文引用: 1]

Subjective cognitive decline (SCD) could indicate preclinical Alzheimer disease but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic. We compared 28 patients from a memory clinic with isolated SCD, 35 community-recruited elders with similarly high levels of self-reported cognitive difficulties and 35 community-recruited controls with low self-reported cognitive difficulties. Increased anxiety and 尾-amyloid deposition were observed in both groups with high self-reported difficulties while subclinical depression and (hippocampal) atrophy were specifically associated with medical help seeking. Cognitive tests showed no group differences. These results further validate the concept of SCD in both community and clinic-based groups. Yet, recruitment methods influence associated biomarkers and affective symptomatology, highlighting the heterogeneous nature of SCD depending on study characteristics.

Perrotin A., Mormino E. C., Madison C. M., Hayenga A. O., & Jagust W. J . (2012).

Subjective cognition and amyloid deposition imaging: A pittsburgh compound b positron emission tomography study in normal elderly individuals.

Archives of Neurology, 69(2), 223-229.

URL     PMID:22332189      Magsci     [本文引用: 1]

OBJECTIVE: To study the relationship between subjective cognition and the neuropathological hallmark of Alzheimer disease (AD), amyloid-尾 (A尾) deposition, using carbon 11-labeled Pittsburgh Compound B (PiB) positron emission tomography in normal elderly individuals. DESIGN: Cross-sectional analysis. SUBJECTS: Forty-eight cognitively normal elderly subjects (11 with high PiB uptake and 28 with low PiB uptake) were included. All underwent clinical and neuropsychological evaluations, magnetic resonance imaging, and positron emission tomography. SETTING: Berkeley Aging Cohort Study. MAIN OUTCOME MEASURE: Relationship between PiB uptake and subjective cognition measures. RESULTS: Subjects with high PiB uptake showed significantly lower performance than those with low PiB uptake on an episodic memory measure and were less confident about their general memory abilities when required to evaluate themselves relative to other people of the same age. High and low PiB uptake groups did not differ on the accuracy of their cognitive self-reports compared with objective cognitive performance. General memory self-reports from the whole group were significantly correlated with regional PiB uptake in the right medial prefrontal cortex and anterior cingulate cortex and in the right precuneus and posterior cingulate cortex. Reduced confidence about memory abilities was associated with greater PiB uptake in these brain regions. All results were independent of demographic variables and depressive affects. CONCLUSIONS: A decrease of self-confidence about memory abilities in cognitively normal elderly subjects may be related to the neuropathological hallmark of AD measured with PiB-positron emission tomography. Subjective cognitive impairment may represent a very early clinical manifestation of AD.

Pike K. E., Amina Z., Ben O., Sarah P., & Kinsella G. J . (2015).

Reduced benefit of memory elaboration in older adults with subjective memory decline.

Journal of Alzheimer’s Disease, 47(3), 705-713.

URL     PMID:26401705      [本文引用: 1]

Cognitive interventions for neurodegenerative diseases, such as Alzheimer's disease (AD), are best targeted at the preclinical stages, and subjective memory decline (SMD) without objective memory impairment on standard tests in older adults may represent a very early preclinical stage. Elaborated encoding effectively enhances memory performance for healthy older adults (HOAs), but has not been examined in people with SMD.To examine elaborated encoding in people with SMD, compared with HOAs.Participants were 32 HOAs and 22 people with SMD, defined using the Memory Complaint Questionnaire. Participants completed a verbal paired associate learning (PAL) task with delayed recall under elaborated and non-elaborated encoding conditions, as well as the California Verbal Learning Test-II.On the PAL learning trials, with age controlled, a significant interaction of group X encoding condition emerged, F(1, 51)66= 666.47, MSE66=666.54, p66=660.014, ηp266=660.11. Simple main effects revealed no differences between groups in the non-elaborated condition, but in the elaborated condition HOAs recalled more pairs than SMD, although both groups benefited from elaboration. At delayed recall, HOA recalled more pairs than SMD, F(1, 51)66= 664.59, p66=660.037, ηp266=660.08, and both groups benefited from elaboration, F(1, 52)66= 6619.25, p66< 660.001, ηp266=660.27.People with SMD benefit from elaborated encoding, although not to the same extent as HOAs. This objective difference in complex learning and memory suggests neural changes in SMD that may represent preclinical AD. Elaborated encoding is a promising technique to help maintain memory and decrease anxiety in this at-risk population.

Rabin L. A., Smart C. M., Crane P. K., Amariglio R. E., Berman L. M., & Boada M ., et al. Sikkes, S. A. M. (2015).

Subjective cognitive decline in older adults: An overview of self-report measures used across 19 international research studies.

Journal of Alzheimer’s Disease, 48(s1), 63-86.

URL     PMID:26402085      [本文引用: 2]

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.

Rami L., Sala-llonch R., Solé-padullés C., Fortea J., Olives J., Lladó A ., et al. Molinuevo, J. L. (2012).

Distinct functional activity of the precuneus and posterior cingulate cortex during encoding in the preclinical stage of Alzheimer's disease.

Journal of Alzheimers Disease, 31(3), 517-526.

Magsci     [本文引用: 2]

In this study functional magnetic resonance imaging (fMRI) is used to investigate the functional brain activation pattern in the preclinical stage of AD (pre-AD) subjects during a visual encoding memory task. Thirty subjects, eleven in the pre-AD stage, with decreased cerebrospinal fluid levels of A beta(42) (<500 pg/ml), and 19 controls with normal A beta(42) levels (CTR) were included. fMRI was acquired during a visual encoding task. Data were analyzed through an Independent Component Analysis (ICA) and region-of-interest-based univariate analysis of task-related BOLD signal change. From the ICA decomposition, we identified the main task-related component, which included the activation of visual associative areas and prefrontal executive regions, and the deactivation of the default-mode network. The activation was positively correlated with task performance in the CTR group (p < 0.0054). Within this pattern, subjects in the pre-AD stage had significantly greater activation of the precuneus and posterior cingulate cortex during encoding. Subjects in the pre-AD stage present distinct functional neural activity before the appearance of clinical symptomatology. These findings may represent that subtle changes in functional brain activity precede clinical and cognitive symptoms in the AD continuum. Present findings provide evidence suggesting that fMRI may be a suitable biomarker of preclinical AD.

Reisberg B., & Gauthier S. (2008).

Current evidence for subjective cognitive impairment (SCI) as the pre-mild cognitive impairment (MCI) stage of subsequently manifest Alzheimer's disease.

International Psychogeriatrics, 20(1), 1-16.

URL     PMID:18072981      [本文引用: 2]

At the present time, there is increasing recognition and understanding of the mild cognitive impairment (MCI) entity as a stage which is a frequent precursor and harbinger of subsequently manifest Alzheimer's disease (AD) and, perhaps, other related conditions, such as vascular dementia (Gauthieret al., 2006). MCI has been defined in two disparate but generally compatible ways in the current literature (see Reisberget al., 2008 (this issue), for a more complete historical overview of MCI). These two definitional approaches might be termed: (a) the clinical approach to MCI, and (b) the clinical plus psychometric approach to MCI.

Reisberg B., Shulman M. B., Torossian C., Leng L., & Zhu W . (2010).

Outcome over seven years of healthy adults with and without subjective cognitive impairment.

Alzheimer’s & Dementia, 6(1), 11-24.

URL     PMID:3873197      [本文引用: 1]

Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects. A consecutive series of healthy subjects, aged ≥40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14-year interval, were studied and followed up during an 18-year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 ± 9.1 years, was well-educated (mean, 15.5 ± 2.7 years), and cognitively normal (Mini-Mental State Examination, 29.1 ± 1.2). A total of 213 subjects (81.9% of the study population) were followed up. Follow-up occurred during a mean period of 6.8 ± 3.4 years, and subjects had a mean of 2.9 ± 1.6 follow-up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined ( P < .0001). Of NCI decliners, five declined to MCI and two to probable Alzheimer's disease. Of SCI decliners, 71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline demographic variables and follow-up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence interval, 1.9–10.3), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45–0.80). Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects ( P = .0003). These results indicate that SCI in subjects with normal cognition is a harbinger of further decline in most subjects during a 7-year mean follow-up interval. Relevance for community populations should be investigated, and prevention studies in this at-risk population should be explored.

Rodda J. E., Dannhauser T. M., Cutinha D. J., Shergill S. S., & Walker Z . (2009).

Subjective cognitive impairment: Increased prefrontal cortex activation compared to controls during an encoding task.

International Journal of Geriatric Psychiatry, 24(8), 865-874.

URL     PMID:19259973      [本文引用: 1]

The activation differences reported in this study may reflect the employment of compensatory strategies in the face of early AD pathology, although a number of alternative explanations need to be considered. Further studies with larger samples may help to determine whether the observed activation changes are likely to be associated with early neuropathological processes or with other unrelated factors. Copyright 2009 John Wiley & Sons, Ltd.

Rönnlund M., Sundström A., Adolfsson R., & Nilsson L.-G . (2015).

Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance: Evidence from the Betula prospective cohort study.

Alzheimer’s & Dementia, 11(11), 1385-1392.

URL     PMID:25667997      [本文引用: 1]

The objective was to examine whether subjective memory impairment (SMI) predicts all-cause dementia or Alzheimer's disease (AD) in a population-based study with long-term follow-up (median02=021002years). A total of 2043 initially dementia-free participants (≥ 6002years) made three memory ratings (“compared with others”, “compared with five years ago”, and “complaints from family/friends”) at baseline. During follow-up, 372 participants developed dementia (208 with AD). Cox regression revealed that subjective memory impairment ratings predicted all-cause dementia in models adjusting for age and sex (hazard ratio or HR from 2.04 to 3.94), with even higher values for AD (HR from 2.29 to 5.74). The result persisted in models including other covariates, including baseline episodic memory performance, and in analyses restricted to participants with long time to dementia diagnosis (≥ 502years). The findings underscore the usefulness of subjective memory assessment in combination with other factors in identifying individuals at risk for developing dementia.

Rowe C. C., Ellis K. A., Rimajova M., Bourgeat P., Pike K. E., Jones G ., et al. Villemagne, V. L. (2010).

Amyloid imaging results from the Australian imaging, biomarkers and lifestyle (AIBL) study of aging.

Neurobiology of Aging, 31(8), 1275-1283.

Magsci     [本文引用: 1]

<h2 class="secHeading" id="section_abstract">Abstract</h2><p id="simple-para0060">The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimer's Disease Neuroimaging Initiative (ADNI), performed <sup>11</sup>C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimer's disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-ε4 carriers vs 21% in noncarriers) and increased with age, most strongly in ε4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in ε4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Aβ) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline.</p>

Ryu S. Y., Lim E. Y., Na S., Shim Y. S., Cho J. H., Yoon B ., et al. Yang, D. W. (2017).

Hippocampal and entorhinal structures in subjective memory impairment: A combined MRI volumetric and DTI study.

International Psychogeriatrics, 29(5), 785-792.

URL     PMID:28067183     

Background: Subjective memory impairment (SMI) is common among older adults. Increasing evidence suggests that SMI is a risk factor for future cognitive decline, as well as for mild cognitive impairment and dementia. Medial temporal lobe structures, including the hippocampus and entorhinal cortex, are affected in the early stages of Alzheimer's disease. The current study examined the gray matter (GM) volume and microstructural changes of hippocampal and entorhinal regions in individuals with SMI, compared with elderly control participants without memory complaints. Methods: A total of 45 participants (mean age: 70.31 6.07 years) took part in the study, including 18 participants with SMI and 27 elderly controls without memory complaints. We compared the GM volume and diffusion tensor imaging (DTI) measures in the hippocampal and entorhinal regions between SMI and control groups. Results: Individuals with SMI had lower entorhinal cortical volumes than control participants, but no differences in hippocampal volume were found between groups. In addition, SMI patients exhibited DTI changes (lower fractional anisotropy (FA) and higher mean diffusivity in SMI) in the hippocampal body and entorhinal white matter compared with controls. Combining entorhinal cortical volume and FA in the hippocampal body improved the accuracy of classification between SMI and control groups. Conclusions: These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.

Scheef L., Spottke A., Daerr M., Joe A., Striepens N., Kölsch H ., et al. Jessen, F. (2012).

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

Neurology, 79(13), 1332-1339.

URL     PMID:22914828      Magsci     [本文引用: 2]

To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects.[]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested.The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline.The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Seo E. H., Kim H., Choi K. Y., Lee K. H., & Choo I. H . (2017).

Association of subjective memory complaint and depressive symptoms with objective cognitive functions in prodromal Alzheimer's disease including pre-mild cognitive impairment.

Journal of Affective Disorders, 217, 24-28.

URL     PMID:28380342      [本文引用: 1]

Abstract Background: Subjective memory complaints (SMC) and depressive symptoms (SDS) are common in the elderly population. However, the relationship among SMC, SDS, and cognitive function remains unclear. We investigated these associations in the elderly from cognitively normal (CN), pre-mild cognitive impairment (MCI), and amnestic MCI (aMCI) groups. Methods: Participants (CN, 299; pre-MCI, 106; aMCI, 267) underwent comprehensive clinical and neuropsychological assessment. and self-report SMC and SDS questionnaires. SMC and SDS were administered in a self-report format. For each neuropsychological test z-score, stepwise multiple linear regressions were performed to assess the relative contribution of SMC, SDS, and their interactions. Results: SMC are associated with lower objective memory, while SDS are associated with lower psychomotor speed. Interactions between SMC and SDS were significant for tests of memory, executive function, psychomotor speed, and global cognition. Additional analyses revealed that SDS moderated the SMC-cognition relationship such that only individuals with higher SDS showed significant SMC-cognition associations. Limitations: Due to the cross-sectional design, associations among SMC, SDS, and cognitive function was rather weak, albeit significant. Additionally, future biomarker studies, such as those assessing amyloid burden, are needed to explore the mechanisms underlying the relationship among SMC, SDS, and cognitive function. Conclusion: Early identification of individuals at risk for developing abnormal cognitive changes is critical. Our findings from the study involving a large sample of carefully selected participants suggest that SMC and SDS could be used as early detection markers of Alzheimer's disease.

Sherry D.F., &Schacter D.L . (1987).

The evolution of multiple memory systems.

Psychological Review, 94(4), 439-454.

[本文引用: 1]

Sierra-rio A., Balasa M., Olives J., Antonell A., Iranzo A., Castellví M ., et al. Molinuevo, J. L. (2015).

Cerebrospinal fluid biomarkers predict clinical evolution in patients with subjective cognitive decline and mild cognitive impairment.

Neurodegenerative Diseases, 16(1-2), 69-76.

[本文引用: 1]

Simons J.S., &Spiers H.J . (2003).

Prefrontal and medial temporal lobe interactions in long-term memory.

Nature Reviews Neuroscience, 4(8), 637-648.

URL     PMID:12894239      [本文引用: 1]

Cognitive neuroscience has made considerable progress in understanding the involvement of the medial temporal and frontal lobes in long-term memory. Whereas the medial temporal lobe has traditionally been associated with the encoding, storage and retrieval of long-term memories, the prefrontal cortex has been linked with cognitive control processes such as selection, engagement, monitoring and inhibition. However, there has been little attempt to understand how these regions might interact during encoding and retrieval, and little consideration of the anatomical connections between them. Recent advances in functional neuroimaging, neurophysiology, crossed-lesion neuropsychology and computational modeling highlight the importance of understanding how the medial temporal and frontal lobes interact to allow successful remembering, and provide an opportunity to explore these interactions.

Sluimer J. D., van der Flier, W. m., Karas G. B., Fox N. C., Scheltens P., & Barkhof F., & Vrenken H . (2008).

Whole-brain atrophy rate and cognitive decline: Longitudinal MR study of memory clinic patients.

Radiology, 248(2), 590-598.

URL     PMID:18574133      [本文引用: 1]

PURPOSE: To prospectively determine whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer disease (AD) and its association with cognitive decline, and investigate the risk of progression to dementia in initially nondemented patients given baseline brain volume and whole-brain atrophy rate. MATERIALS AND METHODS: This study was IRB approved; written informed consent was obtained; and included 65 AD patients (38 women, 27 men; age, 52-81 years), 45 MCI patients (22 women, 23 men; age, 56-80 years), 27 patients with subjective complaints (12 women, 15 men; age, 50-87 years), and 10 healthy controls (six women, four men; age, 53-80 years). Two magnetic resonance (MR) images were acquired at average interval of 1.8 years +/- 0.7 (standard deviation). Baseline brain volume and whole-brain atrophy rates were measured on three-dimensional T1-weighted MR images (1.0 T; single slab, 168 sections; matrix size, 256 x 256; field of view, 250 mm; voxel size, 1 x 1 x 1.5 mm; repetition time msec/echo time msec/inversion time msec, 15/7/300; and flip angle, 15 degrees ). Associations were assessed by using partial-correlations. Cox proportional hazards models were used to estimate risk of developing dementia. RESULTS: Baseline brain volume was lowest in AD but did not differ significantly between MCI, subjective complaints, and control groups (P > .38). Whole-brain atrophy rates were higher in AD (-1.9% per year +/- 0.9) than MCI (-1.2% per year +/- 0.9, P = .003) patients, who had higher whole-brain atrophy rates than patients with subjective complaints (-0.7% per year +/- 0.7, P = .03) and controls (-0.5% per year +/- 0.5, P = .05). Whole-brain atrophy rate correlated with annualized Mini-Mental State Examination (MMSE) change (r = 0.48, P < .001), while baseline volume did not (r = 0.11, P = .22). Cox models showed that-after correction for age, sex, and baseline MMSE-a higher whole-brain atrophy rate was associated with an increased risk of pro

Smart C. M., Karr J. E., Areshenkoff C. N., Rabin L. A., Hudon C., Gates N ., et al. Wesselman, L. (2017).

Non-pharmacologic interventions for older adults with subjective cognitive decline: Systematic review, meta- analysis, and preliminary recommendations.

Neuropsychology Review, 27(3), 245-257.

URL     PMID:28271346      [本文引用: 1]

Abstract In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

Snitz B. E., Lopez O. L., McDade E., Becker J. T., Cohen A. D., Price J. C ., et al. Klunk, W. E. (2015

a). Amyloid-β imaging in older adults presenting to a memory clinic with subjective cognitive decline: A pilot study.

Journal of Alzheimer’s Disease, 48(1), 151-159.

URL     PMID:26402082      [本文引用: 1]

Subjective cognitive decline (SCD) in otherwise normal aging may be identified via symptom inventories in a research setting ('questionnaire-discovered complaints') or via patients seeking evaluation/services in a clinical setting ('presenting complainers'). Most studies of SCD and amyloid-β (Aβ) imaging to date have used the former approach, with inconsistent results. To test whether 'presenting SCD' participants in an academic memory clinic setting show increased brain Aβ deposition on imaging. Fourteen patients (mean age 68.1, SD 4.0 years) diagnosed with subjective cognitive complaints with normal neuropsychological testing were recruited into a Pittsburgh compound B (PiB)-PET study. Detailed self-report inventories and additional cognitive tests were administered. Results were compared to a reference cohort of cognitively normal volunteers (NC) from an independent neuroimaging study (mean age 73.6, SD 5.8 years). 57% (8/14) of SCD participants were PiB-positive by a sensitive, regionally-based definition, compared to 31% (26/84) of the NC cohort. SCD participants had significantly higher PiB retention (SUVR) than NC in three of six regions of interest: frontal cortex (p66=660.02), lateral temporal cortex (p66=660.02), and parietal cortex (p66=660.04). SCD participants showed measurable deviations on questionnaires reflecting high negative affect (i.e., depressive symptoms and neuroticism). Findings were suggestive that deficits on verbal associative binding may be specific to Aβ-positive versus Aβ-negative SCD. Older participants with SCD presenting to a memory clinic in this pilot study sample have higher brain Aβ deposition compared to normal aging study volunteers unselected on complaints. Further study of presenting SCD are warranted to determine the prognostic significance of Aβ deposition in this context.

Snitz B. E., Weissfeld L. A., Cohen A. D., Lopez O. L., Nebes R. D., Aizenstein H. J ., et al. Klunk, W. E. (2015

b). Subjective cognitive complaints, personality and brain amyloid-beta in cognitively normal older adults.

American Journal of Geriatric Psychiatry, 23(9), 985-993.

URL     PMID:25746485      [本文引用: 1]

Subjective cognitive complaints in otherwise normal aging are common but may be associated with preclinical Alzheimer disease in some individuals. Little is known about who is mostly likely to show associations between cognitive complaints and preclinical Alzheimer pathology. We sought to demonstrate associations between subjective complaints and brain amyloid-β in cognitively normal older adults; and to explore personality factors as potential moderators of this association. Cross-sectional observational study. Clinical neuroimaging research center. Community volunteer sample of 92 healthy older adults, screened for normal cognition with comprehensive neuropsychological evaluation. Subjective cognitive self-report measures included the Memory Functioning Questionnaire (MFQ), Cognitive Failures Questionnaire, and the Subjective Cognitive Complaint Scale. Personality was measured with the NEO Five Factor Inventory. Brain amyloid-β deposition was assessed with Pittsburgh compound B (PiB)-PET imaging. One of three cognitive complaint measures, the MFQ, was associated with global PiB retention (standardized beta02=02610.230, p02= 0.046, adjusting for age, sex and depressive symptoms). Neuroticism moderated this association such that only high neuroticism individuals showed the predicted pattern of high complaint–high amyloid-β association. Evidence for association between subjective cognition and brain amyloid-β deposition in healthy older adults is demonstrable but measure-specific. Neuroticism may moderate the MFQ–amyloid-β association such that it is observed in the context of higher trait neuroticism. Subjective cognitive complaints and neuroticism may reflect a common susceptibility toward psychological distress and negative affect, which are in turn risk factors for cognitive decline in aging and incident Alzheimer disease.

Stewart R., Godin O., Crivello F., Maillard P., Mazoyer B., Tzourio C., & Dufouil C . (2011).

Longitudinal neuroimaging correlates of subjective memory impairment: 4-year prospective community study.

British Journal of Psychiatry, 198(3), 199-205.

URL     PMID:21357878      Magsci     [本文引用: 2]

Complaints about memory are common in older people but their relationship with underlying brain changes is controversial. To investigate the relationship between subjective memory impairment and previous or subsequent changes in white matter lesions and brain volumes. In a community cohort study of 1336 people without dementia, 4-year changes in brain magnetic resonance imaging measures were investigated as correlates of subjective memory impairment at baseline and follow-up. Subjective memory impairment at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampal, cerebrospinal fluid and grey matter volume and with subcortical white matter lesion increases. All associations with volume changes were U-shaped with significant quadratic terms - associations between least decline and subjective memory impairment were potentially explained by lower baseline hippocampal volumes in the groups with least volume change. Associations between hippocampal volume change and subjective memory impairment at follow-up were independent of cognitive decline and depressive symptoms, they were stronger in participants with the apolipoprotein E (APOE) 4 allele and in those without baseline subjective memory impairment. Complaints of poor memory by older people, particularly when new, may be a realistic subjective appraisal of recent brain changes independent of observed cognitive decline.

Striepens N., Scheef L., Wind A., Popp J., Spottke A., Cooper-Mahkorn D ., et al. Jessen, F. (2010).

Volume loss of the medial temporal lobe structures in subjective memory impairment.

Dementia and Geriatric Cognitive Disorders, 29(1), 75-81.

URL     PMID:20110703      [本文引用: 1]

Background/Aims: Subjective memory impairment (SMI) has been suggested as a manifestation of Alzheimer&#x2019;s Disease (AD) preceding mild cognitive impairment (MCI). In this study, we determined the volumes of the hippocampus, the entorhinal cortex (EC) and the amygdala to provide biological evidence for AD in SMI. Methods: Regional volumetric measures were manually traced on 3-Tesla MRI scans. Results: Total brain volume did not differ between the groups. Individuals with SMI had reduced volumes of the hippocampus bilaterally (right p = 0.001; left p &#x003C; 0.001), the bilateral EC (right p = 0.031, left p = 0.006) and the right amygdala (p = 0.01) compared to the control group. Conclusion: Volume reduction of bilateral hippocampus, bilateral EC and right amygdala supports the concept of SMI as a very early manifestation of AD prior to MCI. SMI may indicate awareness of a degenerative process that can still be functionally compensated.

Swinford C. G., Risacher S. L., Charil A., Schwarz A. J., & Saykin A. J . (2018).

Memory concerns in the early Alzheimer's disease prodrome: Regional association with tau deposition.

Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 10, 322-331.

URL     PMID:29780876      [本文引用: 1]

Quantitative assessment of perceived memory functioning may be useful for screening older adults at risk for Alzheimer's disease. Individuals and their informants may provide complementary information relating to the anatomical distribution of tau.

Tepest R., Wang L., Csernansky J. G., Neubert P., Heun R., Scheef L., & Jessen F . (2008).

Hippocampal surface analysis in subjective memory impairment, mild cognitive impairment and Alzheimer's dementia.

Dementia and Geriatric Cognitive Disorders, 26(4), 323-329.

[本文引用: 1]

Tulving E. . (1995).

Organization of memory: Quo vadis?

Journal of Cognitive Neuroscience, 8(3), 839-853.

URL     [本文引用: 1]

research in cognitive psychology and neuropsychology of memory has produced a wealth of data that can be meaningfully ordered with the help of 2 general classes of concepts—memory processes and memory systems / proposes a simple model of organization of memory in which cognitive memory systems are related to one another in terms of the principal processes of encoding, storage, and retrieval / the central assumption of this SPI model—serial, parallel, independent—is that the relations among systems are process specific: information is encoded into systems serially, and encoding in 1 system is contingent on the successful processing of the information in another system; information is stored in different systems in parallel; and information from each system can be retrieved independently of information in other systems (PsycINFO Database Record (c) 2015 APA, all rights reserved)

Umeda S., Akine Y., Kato M., Muramatsu T., Mimura M., Kandatsu S ., et al. Suhara, T. (2005).

Functional network in the prefrontal cortex during episodic memory retrieval.

NeuroImage, 26(3), 932-940.

URL     PMID:15955503      [本文引用: 1]

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.

Vannini P., Hanseeuw B., Munro C. E., Amariglio R. E., Marshall G. A., Rentz D. M ., et al. Sperling, R. A. (2017).

Hippocampal hypometabolism in older adults with memory complaints and increased amyloid burden.

Neurology, 88(18), 1759-1767.

URL     PMID:28381517      [本文引用: 1]

Abstract Objective: To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults. Methods: Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET β-amyloid (Aβ) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Aβ burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Aβ(+) vs Aβ(-)), and the interaction between SMCs and Aβ status as predictors of metabolism. Region-of-interest (ROI) analyses were performed to confirm the whole-brain analyses and to test for additional covariates. Results: Greater SMCs correlated with decreased FDG metabolism in the bilateral precuneus, bilateral inferior parietal lobes, right inferior temporal lobe, right medial frontal gyrus, and right orbitofrontal gyrus. A significant interaction effect between SMCs and amyloid burden was found such that Aβ(+) individuals with increased complaints had decreased FDG metabolism in the bilateral medial temporal lobes. ROI analyses confirmed the voxel-wise analyses result in that decreased precuneus metabolism was associated with greater SMCs regardless of Aβ status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Aβ, even after adjustment for age, hippocampal volume, or depressive symptoms. Conclusions: These data show the relevant role of posterior and anterior midline regions in SMCs in older individuals. Decreased hippocampal metabolism may be a specific marker of subclinical changes in cognition due to amyloid pathology. However, longitudinal studies are needed to determine whether our findings foreshadow clinical decline.

Wang L., Zang Y. F., He Y., Liang M., Zhang X. Q., Tian L. X ., et al. Li, K. C. (2006).

Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI.

NeuroImage, 31(2), 496-504.

URL     PMID:16473024      [本文引用: 1]

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in 鈥渄efault mode network previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.

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