Apolipoprotein E and cognitive performance: a meta-analysis

The epsilon4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer's disease and may also affect cognitive performance in normal aging. Evidence of the presence and magnitude of epsilon4-related cognitive deficits was examined with a meta-analysis of the available literature. Thirty-eight studies were included, and cognitive performance was collapsed into 8 domains. Results indicated significant APOE-epsilon4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-epsilon4 carriers. In addition, older age and APOE-epsilon4 heterozygosity was associated with smaller epsilon4-related impairments. The meta-analysis results suggest that APOE-epsilon4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance.     

Cognitive Functioning in Aging and Dementia: The Kungsholmen Project

The Kungsholmen Project (KP) is a community-based longitudinal study of aging and dementia targeting the 75+ population. In this article, we review empirical studies with a cognitive focus from the KP. The main findings indicate that (a) there is an age-related decline for some cognitive domains (e.g., episodic memory, verbal fluency, visuoconstructive skill, psychomotor speed), but not for others (e.g., primary memory, visuoperceptive skill, motor-hand coordination), (b) multiple individual-difference variables within demographic (e.g., sex, education) life-style (e.g., activity levels), genetic (e.g., apolipoprotein E genotype), and health-related (e.g., vitamin B deficiency, depression, diabetes) domains are related to late-life cognitive functioning, (c) a potential for improving cognitive performance – a reserve capacity – is present also among very old adults, (d) the 2 most common dementia diseases, Alzheimer’s disease (AD) and vascular dementia (VaD), affect cognition in a strikingly similar manner, (e) the role of individual-difference variables in cognitive functioning is markedly reduced in dementia – the pathogenesis itself may overshadow the influence of other variables, and (f) there is a long preclinical period in dementia during which cognitive deficits are detectable. As is true with the other projects represented in this issue, the KP portrays a rather diversified picture of cognitive aging, although systematic patterns are evident with regard to the variability of late-life cognitive functioning.     

Connecting the Many Levels and Facets of Cognitive Aging

Basic cognitive mechanisms, such as the abilities to briefly maintain, focus, and process information, decline with age. Related fields of cognitive aging research have been advancing rapidly, but mostly independently, at the biological, information processing, and behavioral levels. To facilitate integration, this article reviews research on cognitive aging at the different levels, and describes a recent integrative theory postulating that aging-related deficiencies in neurotransmission cause increased noise in information processing and less distinctive cortical representation, which in turn lead to cognitive deficits. Aging-related attenuation of catecholaminergic modulation can be modeled by lowering a neural network parameter to reduce the signal-to-noise ratio of information processing. The performance of such models is consistent with benchmark phenomena observed in humans, ranging from age differences in learning rate, asymptotic performance, and interference susceptibility to intra- and interindividual variability and ability dedifferentiation. Although the details of the conjectured sequence of effects linking neuromodulation to cognitive aging deficits await further empirical validation, cross-level theorizing of the kind illustrated here could foster the coevolution of related fields through cross-level data synthesis and hypothesis testing.     

Social Cognition in Multiple Sclerosis: a Meta-Analysis

Multiple sclerosis (MS) is associated with cognitive decline and impairment in social functioning. Accumulating evidence suggests that patients with MS are impaired in social cognition, including theory of mind (ToM) and emotion recognition. In this meta-analysis of 24 studies, facial emotion recognition and ToM performances of 989 patients with MS and 836 healthy controls were compared. MS was associated with significant impairments with medium effect sizes in ToM (d?=?0.57) and facial emotion recognition (d?=?0.61). Among individual emotions recognition of fear and anger were particularly impaired. The severity of social cognitive deficits was significantly associated with non-social cognitive impairment. These deficits in social cognition may underpin difficulties in social functioning in MS. However, there is a need for further studies investigating the longitudinal evolution of social cognitive deficits and their neural correlates in MS.     

Context processing in older adults: evidence for a theory relating cognitive control to neurobiology in healthy aging.

A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions.     

Processing speed in normal aging: Effects of white matter hyperintensities and hippocampal volume loss

Changes in cognitive functioning are said to be part of normal aging. Quantitative MRI has made it possible to measure structural brain changes during aging which may underlie these decrements which include slowed information processing and memory loss. Much has been written on white matter hyperintensities (WMH), which are associated with cognitive deficits on tasks requiring processing speed and executive functioning, and hippocampal volume loss, which is associated with memory decline. Here we examine volumetric MRI measures of WMH and hippocampal volume loss together in relation to neuropsychological tests considered to be measures of executive functioning and processing speed in 81 non-demented elderly individuals, aged 75–90. Correlational analysis showed that when controlling for age, both greater WMH volume and smaller hippocampal volume were correlated with slower performances on most tests with the exception of a battery of continuous performance tests in which only WMH was correlated with slower reaction time (RT). We then performed a series of hierarchical multiple regression analyses to examine the independent contributions of greater WMH volume and reduced hippocampal volume to executive functioning and processing speed. The results showed that for the four measures requiring executive functioning and speed of processing, WMH volume and hippocampal volume combined predicted between 21.4% and 37% of the explained variance. These results suggest that WM integrity and hippocampal volume influence cognitive decline independently on tasks involving processing speed and executive function independent of age.     

Qualitative attentional changes with age in doing two tasks at once

Does practice reduce, or even eliminate, aging effects on the attentional limitations responsible for dual-task interference? The studies reviewed in this article show that age differences reliably persist after extensive practice. Strikingly, dual-task interference remains larger among older adults even in training conditions that allow them to achieve single-task performance as fast as younger adults. These findings demonstrate that age deficits in attentional functioning are robust. Advancing age also can be accompanied by improvements in cognitive functioning, such as in the ability to access the lexicon without attention (i.e., automatically), due to lifelong experience with word reading. Future research needs to establish whether age deficits in central attention are due to structural changes that are irreversible or reversible to some extent.     

前临床期痴呆的认知特征：当前研究进展和未来研究展望

在这篇文章中, 我将讨论从正常老化到痴呆, 这一通常被称为痴呆前临床阶段的认知功能的转变。研究表明, 阿尔茨海默症和血管性痴呆病人在临床确诊之前的几年中, 会出现明显的认知损伤。早期最突出的损伤存在于情节记忆、加工速度以及执行功能。这些功能性损伤与神经生物学研究证实的边缘系统和新皮层区存在多重损伤是相一致的。虽然早在临床诊段之前, 病人组和控制组的平均成绩存在巨大差异, 但同时这两组测试成绩的分布在很大程度上是重叠的。寻求降低这种重叠度的方法是未来研究的一个重要任务。这有可能通过将认知的和其他指标(如基于脑的、基因的、临床的、社会的)相结合构建预测模型来实现。此外, 在未来研究中以下三方面也是急需考虑问题: (a) 找出在 前临床期间认知功能急速下降的时间点: (b) 评估从前临床到临床诊断变化速率中存在的个体差异; (c) 确定特定因素与随后发生的痴呆之间的关联强度是如何随时间向临床确诊推进而逐渐变化的。     

Which Executive Functioning Deficits Are Associated With AD/HD,ODD/CD and Comorbid AD/HD+ODD/CD?

This study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).     

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior–posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application.     

Cognitive Remediation in Schizophrenia

Cognitive deficits are routinely evident in schizophrenia, and are of sufficient magnitude to influence functional outcomes in work, social functioning and illness management. Cognitive remediation is an evidenced-based non-pharmacological treatment for the neurocognitive deficits seen in schizophrenia. Narrowly defined, cognitive remediation is a set of cognitive drills or compensatory interventions designed to enhance cognitive functioning, but from the vantage of the psychiatric rehabilitation field, cognitive remediation is a therapy which engages the patient in learning activities that enhance the neurocognitive skills relevant to their chosen recovery goals. Cognitive remediation programs vary in the extent to which they reflect these narrow or broader perspectives but six meta-analytic studies report moderate range effect sizes on cognitive test performance, and daily functioning. Reciprocal interactions between baseline ability level, the type of instructional techniques used, and motivation provide some explanatory power for the heterogeneity in patient response to cognitive remediation.     

Cholinergic-dopaminergic interactions in cognitive performance

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.     

Purpose in life and cognitive functioning in adulthood

With an increasingly aging population, more work is needed to identify factors which may promote the maintenance of normal cognitive functioning. The current study tested the concurrent association between sense of purpose in life and the cognitive variables of episodic memory, executive functioning, and composite cognitive functioning in adults (N = 3489, M_age = 56.3 years, SD = 12.27, Range = 32–84 years) from the Midlife in the United States study (MIDUS). Correlational analyses suggested that purpose in life was associated with higher scores for memory, executive functioning, and overall cognition. Bootstrapping tests of moderation found no evidence for a moderating effect of age on purpose and the cognitive variables. Future studies should attempt to explain the mechanisms behind this relationship and explore the potential for interventions to promote healthy cognitive and purposeful aging.     

Mental Exercise and Mental Aging

ABSTRACT— It is widely believed that keeping mentally active will prevent age-related mental decline. The primary prediction of this mental-exercise hypothesis is that the rate of age-related decline in measures of cognitive functioning will be less pronounced for people who are more mentally active, or, equivalently, that the cognitive differences among people who vary in level of mental activity will be greater with increased age. Although many training studies, and comparisons involving experts, people in specific occupations, and people whose mental activity levels are determined by their self-reports, have found a positive relation between level of activity and level of cognitive functioning, very few studies have found an interactive effect of age and mental activity on measures of cognitive functioning. Despite the current lack of empirical evidence for the idea that the rate of mental aging is moderated by amount of mental activity, there may be personal benefits to assuming that the mental-exercise hypothesis is true.     

Pessimistic self-preoccupation, performance deficits, and depression

Three studies are presented testing a model of the cognitive performance deficits shown in depression. The model proposes that such deficits occur as an interaction of expectancy and focus of attention variables, that is, in the presence of both low expectancy of success and high self-focus. Study 1 was a pilot study which documented that depressed undergraduates evidence poorer anagram performance, greater self-focus, and lower pretask expectancies than do nondepressed subjects. Study 2 showed that nondepressed undergraduates evidence performance deficits only when both expectancy is lowered and self-focus is increased. Study 3 suggested that depressed undergraduates' performance deficits are overcome either by lowering self-focus or by raising expectancy. Discussed are discrepancies between self-report and performance data, the relevance of these studies to the test anxiety literature, the need to integrate literature concerning the effects of depression, anxiety, and self-esteem on performance, and how the interactive roles of positive expectancy and focus of attention may be related to effective coping in a variety of situations.     

Planning and realization of complex intentions in traumatic brain injury and normal aging

The realization of delayed intentions (i.e., prospective memory) is a highly complex process composed of four phases: intention formation, retention, re-instantiation, and execution. The aim of this study was to investigate if executive functioning impairments are related to problems in the formation, re-instantiation, and execution of a delayed complex intention. In this context, it was another aim of the study to investigate the executive functioning hypothesis of cognitive aging in prospective memory performance. It was, therefore, explored if age-related prospective memory decline leads to similar decrements in the process of prospective remembering as executive functioning-related decline in young patients with traumatic brain injury. A group of patients with traumatic brain injury with retrospective memory within normal limits but impaired executive functions, a group of healthy older and a group of healthy younger adults completed a complex prospective memory task that allows for the separate assessment of the four phases of the prospective memory process. All groups showed a similarly high performance in the intention retention phase, whereas the patients with deficits in executive functioning and the older participants performed worse than the healthy young participants in the intention formation, re-instantiation and execution phases. The importance of executive functioning for prospective remembering in traumatic brain injury and normal aging is discussed.     

Neuropsychological correlates of psychopathic traits in a non-incarcerated sample

The present study examined the association between neuropsychological behavioral performance and psychopathic personality traits, measured via the Psychopathic Personality Inventory (PPI), in a non-incarcerated sample. Specifically, performance involving general executive cognitive functioning (ECF) and response inhibition was investigated in regards to the two main psychopathy factors (affective-interpersonal and social deviance) of the PPI. A group of 95 student volunteers were administered the PPI and a variety of neuropsychological measures. Analyses revealed that total PPI scores were related to deficits in response inhibition but not general ECF. However, this relationship was qualified by the differential associations observed for the two PPI factors. The social deviance factor was associated with deficits in general ECF and response inhibition, whereas the affective-interpersonal facet was associated with enhanced general ECF performance but not response inhibition. The results suggest that cognitive functioning shows predicted associations with a self-report measure of psychopathy among non-incarcerated young adults, providing further evidence for psychopathy conceptualizations from a normal-range personality perspective.     

Behavioral dysexecutive symptoms in normal aging

Executive deficits of normal aging such as deficits in planning, organization or decision making are likely to affect elderly individuals in their daily life functioning. Therefore, executive functioning in aging seems to be interesting to study not only in cognitive terms but also in relation to the behavioral area. This pilot study aimed to investigate the nature of behavioral dysexecutive problems in a sample of normal elderly adults as measured by the Dysexecutive Questionnaire. Factor analysis showed that five interpretable factors could be derived from the DEX: intentionality (factor 1), interference management (factor 2), inhibition (factor 3), planning (factor 4), and social regulation (factor 5), suggesting that different components may underlie the behavioral dysexecutive symptoms of normal aging. The relationship between these factors and neuropsychological measures of Executive Functions were also briefly explored.     

Productive syntax abilities in Huntington's and Parkinson's diseases

This study examined syntactic changes in the spoken discourse of patients with Huntington's (HD) or Parkinson's disease (PD) and explored possible relationships between their syntactic changes and concomitant cognitive and motoric symptoms. Patient and control groups participated in a conversational discourse activity and completed a battery of standardized speech and cognitive tests. The HD group used shorter and fewer grammatically complete utterances than their healthy, age-matched peers, whereas there were no significant syntactic differences between PD patients and their healthy, age-matched peers or between PD and HD patients. Productive syntax abilities in HD and PD were meaningfully related to both neuropsychological and motor speech changes. These findings indicate that patients with subcortical disease, at least those with HD, may present with language production deficits and that these deficits are most likely the product of not only motor speech limitations (i.e., dysarthria) but also underlying cognitive impairments.     

Executive functioning in older adults with mild cognitive impairment: MCI has effects on planning, but not on inhibition

In this study, we compared executive functioning in 32 mild cognitive impairment (MCI) individuals with that of normally aging controls. Cognitive planning tests (Trail Making, Porteus Maze Test, verbal fluency tests) show a group difference favoring the normal controls, but tests for inhibition of prepotent responses (no-go accuracy, two measures of the Stroop effect, and negative priming) failed to uncover a significant group difference. The results indicate that there is no general executive control function impairment in MCI; rather, the deficits found are compatible with the hypothesis that MCI is an accelerated form of normal aging.