Effects of Hormone Replacement Therapy and Aging on Cognition: Evidence for Executive Dysfunction

ABSTRACT

The present study was designed to explore whether the frontal lobe hypothesis of cognitive aging may be extended to describe the cognitive effects associated with estrogen use in postmenopausal women. Postmenopausal estrogen-only users, estrogen + progesterone users, and non-users (60–80 years old), as well as young, regularly cycling women (18–30 years old) completed an item and source memory task. Since source memory is thought to rely more on executive processes than item memory, we hypothesized that aging and estrogen effects would be greater for source memory than for item memory. Neuropsychological tests explored whether the effects of aging and estrogen use were revealed on other tests of frontal lobe function. Results from the experimental task revealed greater aging and estrogen effects for source memory than for item memory, and neuropsychological results revealed aging and estrogen effects on a subset of tests of executive function. Women on estrogen + progesterone therapy did not outperform non-users, suggesting that the addition of progesterone to hormone therapy may mitigate the benefits induced by estrogen use alone. Overall, findings support the hypothesis that estrogen use may temper age-related cognitive decline by helping to maintain functions subserved by the frontal lobes.     

Do young and older adults rely on different processes in source memory tasks? A neuropsychological study

Source memory has consistently been associated with prefrontal function in both normal and clinical populations. Nevertheless, the exact contribution of this brain region to source memory remains uncertain, and evidence suggests that processes used by young and older adults may differ. The authors explored the extent to which scores on composite measures of neuropsychological tests of frontal and medial temporal function differentially predicted the performance of young and older adults on source memory tasks. Results indicated that a frontal composite measure, consistently associated with source memory performance in older adults, was unrelated to source memory in young adults, although it was sensitive to a demanding working memory task. The memory composite score, however, predicted performance in the young group. In addition, item and source memory were correlated in young but not older people. Findings are discussed in terms of age-related differences in working memory and executive functions, and differential binding processes necessary for item and source memory. The requirement to integrate item and source information at encoding appears to place greater demands on executive or working memory processes in older adults than in younger adults.     

Positive mood and executive function: evidence from stroop and fluency tasks

Contrasting predictions have been made about the effects of positive mood states on the performance of frontal lobe tests that tap executive functions such as inhibition, switching, and strategy use. It has been argued that positive mood is likely to improve some cognitive processes, particularly those dependent on the frontal cortex and anterior cingulate of the brain. However, there is some evidence that happy mood may impair executive functioning. The current experiments investigated the effects of positive mood on Stoop and fluency tests, which are frequently used to assess executive function. Positive mood impaired performance on a switching condition of the Stroop test, but improved performance on a creative uses test of fluency. The effect of positive mood on an executive task may therefore depend on whether a task is inherently motivating or is impaired by diffuse semantic activation.     

Executive functioning and processing speed in age-related differences in time estimation: a comparison of young,old, and very old adults

Age-related differences in time estimation were examined by comparing the temporal performance of young, young–old, and old–old adults, in relation to two major theories of cognitive aging: executive decline and cognitive slowing. We tested the hypothesis that processing speed and executive function are differentially involved in timing depending on the temporal task used. We also tested the assumption of greater age-related effects in time estimation in old–old participants. Participants performed two standard temporal tasks: duration production and duration reproduction. They also completed tests measuring executive function and processing speed. Findings supported the view that executive function is the best mediator of reproduction performance and inversely that processing speed is the best mediator of production performance. They also showed that young–old participants provide relatively accurate temporal judgments compared to old–old participants. These findings are discussed in terms of compensation mechanisms in aging.     

Does Estrogen Protect Against Cognitive Aging in Women?

ABSTRACT— Although there is evidence from randomized controlled trials that estrogen therapy protects against aspects of cognitive decline that occur with normal aging in women, findings from the Women's Health Initiative Memory Study and from some cross-sectional and longitudinal studies failed to find neuroprotective effects of estrogen in older women. There is growing empirical support for the critical-period hypothesis, formulated in the attempt to resolve these discrepancies. It holds that estrogen therapy has protective effects on verbal memory and on working memory only when it is initiated closely in time to menopause, whereas starting treatment many years following menopause does not protect and may even be harmful. Supporting evidence for this hypothesis from basic neuroscience and from animal and human studies is evaluated for its ability to explain the inconsistencies and to describe the conditions under which estrogen may protect cognitive function in aging women.     

Explaining neurocognitive aging: is one factor enough?

As an introduction to the special issue on neurocognitive factors underlying age effects, we discuss a number of recent developments in the literature on aging. The classic distinction between generalized and process-specific cognitive changes with old age has reappeared in the distinctions between the frontal lobe hypothesis and more differentiated views of neurocognitive aging. We argue that neurological decay in the frontal cortex has important implications for cognitive control, but that the frontal lobe hypothesis does not capture the plethora of changes that characterize aging and incorrectly suggests a unitary effect.     

The neural basis of updating: Distinguishing substitution processes from other concurrent processes

Sörqvist, P. & Sætrevik, B. (2010). The neural basis of updating: Distinguishing substitution processes from other concurrent processes. Scandinavian Journal of Psychology, 51, 357–362. Most previous studies of updating processes have not been able to contrast processes of substituting items in memory with other concurrent processes. In the present investigation, we used a new task called “number updating” and an fMRI protocol to contrast the activation of trials that require item substitution (adding a new item to the working memory representation and suppressing an old item) with trials that involve no substitution (discarding the new item). Trials that require item substitution activated the dorsolateral prefrontal cortex, the posterior medial frontal cortex and the parietal lobes, areas typically seen activated for working memory tasks in general. Trials that do not require substitution activated the anterior medial frontal cortex. Studies examining executive functions have associated this area with cognitive conflict, and may represent suppression of the substitution processes.     

Subtle cognitive deficits in severe alcohol addicts – Do they show a specific profile?

Although alcohol dependency is a burden to society, data on cognitive performance in therapy‐resistant patients after multiple withdrawals are poor. In this study, 22 patients without reported cognitive deficits and 20 control subjects performed extensive cognitive testing and a motor task assessing short‐term memory. Patients displayed subtle deficits (mainly in executive function), while memory functions were relatively unimpaired. Our results suggest that subtle frontal‐executive deficits may contribute to a poor prognosis, but could be missed by routine clinical tests.     

贫困对个体执行功能的影响

已有研究发现,贫困会对个体的执行功能产生消极的影响,这种影响贯穿于个体婴儿期、童年期以及成年期。贫困会影响与执行功能相关的前额叶的结构（如较小的灰质体积）。贫困个体与非贫困个体对额叶区域资源的调用方式不同,贫困个体需要使用额外的补偿资源来监测和抑制对干扰物的反应。贫困会通过压力、认知剥夺以及父母养育等因素直接或间接的影响个体的执行功能。今后该领域的研究应关注贫困影响执行功能的调节变量（如自我肯定、自我调节）,建立贫困影响执行功能的综合模型（如考虑贫困经历时间等）,立足执行功能的可塑性,通过认知干预提高贫困个体的执行功能。     

Age,working memory,and the Tower of London task

The current study explores the role of three components of working memory in age differences in an executive task, the Tower of London (TOL). The TOL task is sensitive to frontal lobe damage, and is widely used to measure planning ability. Dual tasks were used to test the involvement of the phonological loop (articulatory suppression), visuospatial buffer (pattern tapping), and central executive (random generation) in age effects on the TOL. Older adults showed greater reliance than young on domain-specific verbal and spatial memory components in performing the TOL. In terms of executive function, qualitatively different interference patterns were seen in young and old participants. However, the validity of using random generation tasks to assess executive function in older populations can be questioned. For older participants, performing the TOL loads all components of working memory, whereas for the younger participants the TOL more specifically loads executive functioning.     

2～3.5岁儿童执行功能发展特点及其言语能力的影响

2~3.5岁是婴儿成长到幼儿的重要发展转折期,也是儿童执行功能及言语能力的发展萌芽期。研究通过测查北京市81名2~3.5岁儿童在固定盒子任务、搭积木任务、A非B任务和皮博迪图片词汇测验上的表现,探究了该年龄段儿童执行功能的发展特点、各成分间的内部关系、以及言语能力对执行功能的影响。结果发现:(1)在2~3.5岁期间,除认知灵活性外,儿童的工作记忆与抑制控制均快速发展,其中,2.5岁前后是工作记忆与抑制控制的重要发展时期;(2)在2~3岁期间,认知灵活性与工作记忆之间相关密切,在3~3.5岁期间,认知灵活性与抑制控制的相关密切,3岁是儿童执行功能内部成分关系的重要发展转折期;(3)在2~3.5岁期间,儿童言语能力呈现快速发展,并且言语能力对该年龄段执行功能各成分间关系产生一定的影响,但不同言语能力的儿童在执行功能各成分的表现并没有显著差异。     

Frontal deficits in alcoholism: an ERP study

Alcoholism is a major health problem afflicting people all over the world. Understanding the neural substrates of this addictive disorder may provide the basis for effective interventions. So-called "executive processes" play a role in cognitive functions like attention and working memory, and appear to be disrupted in alcoholism (Noel et al., 2001). Event related potentials (ERPs) provide an excellent, minimally invasive technique for exploring these neural deficits. The current study used the P300 in number sequencing task (modified version of the Petries & Milner, 1982) requiring working memory to compare a group of patients with alcoholism and frontal lobe lesions to patients with subcortical lesions and normal controls to assess the relationship of alcoholism to frontal lobe damage. The ERP paradigm was a Number Sequencing task. Electrophysiological results indicate that the frontal lesion group had significant P300 amplitude reduction and a similar trend for alcohol dependent group but not the subcortical group compared to the normal controls.     

Effects of frontal lobe damage on interference effects in working memory

Working memory is hypothesized to comprise a collection of distinct components or processes, each of which may have a unique neural substrate. Recent neuroimaging studies have isolated a region of the left inferior frontal gyrus that appears to be related specifically to one such component: resolving interference from previous items in working memory. In the present study, we examined working memory in patients with unilateral frontal lobe lesions by using a modified version of an item recognition task in which interference from previous trials was manipulated. In particular, we focused on patient R.C., whose lesion uniquely impinged on the region identified in the neuroimaging studies of interference effects. We measured baseline working memory performance and interference effects in R.C. and other frontal patients and in age-matched control subjects and young control subjects. Comparisons of each of these groups supported the following conclusions. Normal aging is associated with changes to both working memory and interference effects. Patients with frontal damage exhibited further declines in working memory but normal interference effects, with the exception of R.C., who exhibited a pronounced interference effect on both response time and accuracy. We propose that the left inferior frontal gyrus subserves a general, nonmnemonic function of selecting relevant information in the face of competing alternatives and that this function may be required by some working memory tasks.     

Impact of executive dysfunctions on episodic memory abilities in patients with ruptured aneurysm of the anterior communicating artery

Executive and memory dysfunctions are among the most frequently reported deficits following a ruptured aneurysm of the anterior communicating artery (ACoA). In order to study the impact of the dysexecutive syndrome on episodic and semantic memory, the data obtained from 59 ACoA patients were examined retrospectively. All patients were assessed on a variety of episodic memory tests (Rey Auditory-Verbal Learning Test, Rey Complex Figure Test, Weschler Memory Scale), semantic memory (verbal fluency), and standardized tests of executive functions (Trail Making Test, Maze tests, Wisconsin Card Sorting Test). There was a strong positive correlation between executive dysfunction and retrieval difficulties in episodic and semantic memory tasks. Comparisons of subgroups of patients with high and low frontal lobe functioning on delayed recall and recognition revealed a significant group X condition interaction in addition to significant group and condition main effects. ACoAs patients with low frontal lobe functioning were particularly deficient in free recall (immediate and delayed) while recognition was equally well preserved in the two subgroups. Neither subgroup presented with an abnormal forgetting over time suggesting a retrieval deficit rather than a true retention impairment.     

不同情绪背景下来源记忆的ERPs研究*

使用事件相关电位(ERP)技术和测试来源记忆的多键范式,探讨不同情绪效价背景下来源提取的认知神经机制。学习阶段,同时呈现汉字和3种效价情绪图片(重叠);测验阶段,只呈现汉字,要求被试进行四键判断：旧字且背景为中性,旧字且背景为正性,旧字且背景为负性,新字。结果发现：在提取阶段,刺激呈现后300~500 ms,3种情绪背景下来源判断正确项目和来源判断错误项目都比新项目诱发了更正的ERPs(即都存在新旧效应),这一结果反映出刺激呈现后300~500 ms 是一个早期的项目提取阶段,它独立于来源提取。并且,在中性背景下,两种新旧效应没有差别;而在正性和负性背景下,来源判断正确项目的新旧效应显著大于来源判断错误项目。说明相比于中性背景,情绪背景下被试可能更早对来源信息产生熟悉感。在500~650 ms,3种情绪背景下都存在来源判断正确项目的新旧效应,在来源判断错误项目和新项目之间没有显著差异,来源正确与来源错误有显著的新旧效应差异,但二者在头皮分布上是类似的,这反映了晚期的来源提取过程。同时来源正确的新旧效应在这两个时段有显著不同的头皮分布,表明这两个时段有不同加工过程。另外,在500~650 ms,存在显著的情绪效应,正性背景下正确判断来源诱发的ERPs比中性和负性背景下的更正,而且来源判断错误条件下没有情绪效应。综上所述,来源正确和来源错误可能仅仅反映了大脑激活在量上的不同,并不能推断两者存在质的差异;大脑神经活动的早期不仅反映了对记忆项目的熟悉性,而且也受情绪效应的影响,500 ms之后大脑神经活动反映的是对记忆项目回想的过程,这一回想过程也与情绪效应有关,受到情绪效应的调节。     

编码任务对来源记忆的影响:一项事件相关电位研究

本研究采用ERPs技术,探讨编码任务对来源记忆的影响及其神经机制。在学习阶段,被试进行两种编码操作：匹配判断任务和大小判断任务;在测验阶段,让被试进行来源判断任务。行为结果发现：在编码阶段,匹配判断任务比大小判断任务需要更长的时间;在测验阶段,匹配判断任务在“项目旧/背景旧”和“部分旧”条件的正确率显著高于大小判断任务,匹配判断任务在“项目旧/背景旧”条件的反应时显著短于大小判断任务。测验阶段ERPs结果发现：两种编码任务的新旧效应在200~700ms均有较广泛的头皮分布,而在700~1100ms呈前额皮层最大化分布;匹配判断任务的新旧效应比大小判断任务更大,表现在600~700ms的FPz电极以及700~800ms的Pz、P4电极。由此可见,在来源记忆中,编码任务影响来源记忆,主要表现在后部顶区位置;晚期前额皮层新旧效应不受任务难度因素的影响。     

Age effects on different components of theory of mind

The effects of aging on the cognitive and affective dimensions of theory of mind (ToM), and on the latter’s links with other cognitive processes, such as information processing speed, executive functions and episodic memory, are still unclear. We therefore investigated these effects in young (n = 25), middle-aged (n = 20) and older adults (n = 25), using separate subjective and objective assessment tasks. Furthermore, a novel composite task probed participants’ abilities to infer both cognitive and affective mental states in an interpersonal context. Although age affected the objective ToM tests, results revealed a direct aging effect on the second-order ToM, but an indirect one on the first-order cognitive ToM, mediated mainly by age-related declines in executive functions. This study supports the notion of an age-related distinction between subjective and objective assessments of ToM, and confirms that ToM is a complex mental ability with several characteristics reliant to some extent on executive processes.     

Brain activation patterns in major depressive disorder and work stress-related long-term sick leave among Swedish females

Deficits in executive functioning and working memory associated with frontal lobe dysfunction are prominent in depression and work-related long-term sick leave (LTSL). This study used functional magnetic resonance imaging (fMRI) to investigate potential differences in brain activation patterns in these conditions. In addition, the function of the hypothalamic-pituitary-adrenal (HPA) axis was examined and compared between groups. Since there is a clear overrepresentation of women in these diagnostic groups, and to ensure a more homogenous sample population, only women were included. To examine the neural correlates of relevant cognitive processes in patients on sick leave >90 days due to work-related LTSL, recently diagnosed patients with major depression Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria, untreated), and healthy controls (n?=?10, each group), a 2-back working memory task and a visual long-term memory task were administered during fMRI scanning. HPA axis functioning was investigated using a diurnal curve of saliva cortisol and a dexamethasone suppression test. Task performance was comparable among the three groups. Multivariate image analysis revealed that both memory tasks engaged a similar brain network in all three groups, including the prefrontal and parietal cortex. During the 2-back task, LTSL patients had significant frontal hypoactivation compared to controls and patients with depression. Saliva cortisol measurements showed a flattening of the diurnal rythmicity in LTSL patients compared to patients with depression and healthy contols. Taken together, these findings indicate that work stress-related LTSL and major depression are dissociable in terms of frontal activation and diurnal cortisol rhythmicity.     

Les capacités d'inhibition : une fonction « frontale » ?

It has been strongly suggested that one important function related to frontal lobes is inhibition. However, a review of the literature on classical tests of inhibition (Stroop test, WCST, and AB-AC learning) suggests that this hypothesis is not well established. We further examined this hypothesis using short-term and long-term directed forgetting tasks (Reed, 1970, Zacks et al., 1996), the Stroop test and the Hayling test (Burgess and Shallice, 1996) in 13 patients with focal frontal lesions. The results revealed short-term and long-term memory deficits and a slowing down, but no inhibition deficit compared with control subjects. These results question the relevance of the hypothesis of the frontal lobe as the unique substrate of inhibitory mechanisms. More generally, they address the issue of executive functions: are these sustained by the frontal cortex or by a cortical and subcortical diffuse neural network?