Only time will tell: cross-sectional studies offer no solution to the age-brain-cognition triangle: comment on Salthouse (2011)

Salthouse (2011) critically reviewed cross-sectional and longitudinal relations among adult age, brain structure, and cognition (ABC) and identified problems in interpretation of the extant literature. His review, however, missed several important points. First, there is enough disparity among the measures of brain structure and cognitive performance to question the uniformity of B and C vertices of the ABC triangle. Second, age differences and age changes in brain and cognition are often nonlinear. Third, variances and correlations among measures of brain and cognition frequently vary with age. Fourth, cross-sectional comparisons among competing models of ABC associations cannot disambiguate competing hypotheses about the structure and the range of directed and reciprocal relations between changes in brain and behavior. We offer the following conclusions, based on these observations. First, individual differences among younger adults are not useful for understanding the aging of brain and behavior. Second, only multivariate longitudinal studies, age-comparative experimental interventions, and a combination of the two will deliver us from the predicaments of the ABC triangle described by Salthouse. Mediation models of cross-sectional data represent age-related differences in target variables but fail to approximate time-dependent relations; thus, they do not elucidate the dimensions and dynamics of cognitive aging.     

Between-individual variability and interpretation of associations between neurophysiological and behavioral measures in aging populations: comment on Salthouse (2011)

Salthouse (2011) argued that (a) variance between individuals on cognitive test scores remains constant between 20 and 90 years of age and (b) widely recognized problems of deducing functional relationships from patterns of correlations between measurements become especially severe for neuropsychological indices, especially for gross indices of age-related brain changes (e.g., losses of brain volume or increases in white matter lesions). I argue that between-individual variability on cognitive tests does increase with age and provides useful information on causes of age-related cognitive decline. I suggest that problems of inference from correlations are just as difficult for behavioral as for neurophysiological indices and that inclusion, in analyses, of even gross measures of brain status such as loss of volume and white matter lesions can correct misinterpretations that occur when only behavioral data are examined.     

White matter development during adolescence as shown by diffusion MRI

Previous volumetric developmental MRI studies of the brain have shown white matter development continuing through adolescence and into adulthood. This review presents current findings regarding white matter development and organization from diffusion MRI studies. The general trend during adolescence (age 12–18 years) is towards increasing fractional anisotropy (FA) with age and decreasing mean diffusivity (MD) with age, findings primarily due to decreasing radial diffusivity with age. However, results of studies vary as to the regional specificity of such age-related changes, likely due in part to methodological issues. Another general trend is for FA to positively correlate and MD to negatively correlate with cognitive function. This trend is however region-specific, task-specific, and population-specific; some studies have in fact found negative correlations of FA and positive correlations of MD in specific regions with specific measures of cognitive performance. There are also published reports of sexual dimorphism in white matter development, indicating differing developmental trajectories between males and females as well as differing relationships developmentally between white matter architecture and cognitive function. There is a need for more research to further elucidate the development of white matter and its relation to cognitive function during this critical developmental period.     

长期高策略性技能训练对运动员大脑白质结构的影响：一项DTI研究

目前关于运动员经验优势的脑机制还存在争议, 尤其对于涉及较多认知过程参与的高策略性技能项目运动员, 其大脑白质结构可塑性变化还需进一步探究。研究横向对比了乒乓球运动员和非运动员大脑白质纤维束的弥散张量成像数据。结果发现, 相比于非运动员, 乒乓球运动员在连接背侧和腹侧通路脑区的双侧皮质脊髓束、左侧上纵束、左侧下纵束和双侧额枕下束的各向异性值(FA)更大, 进一步分析发现, 部分腹侧通路白质纤维束FA增加的原因是径向扩散系数(RD)下降。研究结果支持了动作双通路模型。提示经过长期高策略性技能训练, 乒乓球运动员在背侧和腹侧通路上的白质纤维束结构完整性增强。     

All data collection and analysis methods have limitations: reply to Rabbitt (2011) and Raz and Lindenberger (2011)

The commentaries on my article contain a number of points with which I disagree but also several with which I agree. For example, I continue to believe that the existence of many cases in which between-person variability does not increase with age indicates that greater variance with increased age is not inevitable among healthy individuals up to about 80 years of age. I also do not believe that problems of causal inferences from correlational information are more severe in the cognitive neuroscience of aging than in other research areas; I contend instead that neglect of these problems has led to confusion about neurobiological underpinnings of cognitive aging. I agree that researchers need to be cautious in extrapolating from cross-sectional to longitudinal relations, but I also note that even longitudinal data are limited with respect to their ability to support causal inferences.     

Structural Imaging Measures of Brain Aging

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.     

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.     

Structural constraints on process explanations in cognitive aging

Much of the current research in the area of cognitive aging has been focused on investigating specific processes presumed to be responsible for the age differences observed in particular cognitive tasks. A central thesis of this article is that age-related effects on cognitive variables seldom occur in isolation, and hence, they are best interpreted in the context of the structural interrelations that exist among variables and the relations of age on that organizational structure. Results from analyses of 2 separate data sets suggest that large proportions of the age-related effects across a wide range of cognitive variables are shared and that independent, or unique, age-related effects often contribute relatively little to the age differences observed in many cognitive variables. These findings imply that it is important to consider the structure within which a variable occurs when attempting to investigate the processes responsible for age-related differences on that variable.     

White matter maturation supports the development of reasoning ability through its influence on processing speed

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability.     

What needs to be explained to account for age-related effects on multiple cognitive variables?

Structural equation methodology was used to investigate age-related influences across a number of cognitive variables in 204 adults ranging from 18 to 91 years of age with a hierarchical structure that contained 4 1st-order factors and 1 2nd-order common factor. Direct age relations were found to the common factor as well as to 1st-order speed and memory factors. Replicability of the findings was explored by investigating the same structure of age relations, using 2 different data sets, and a similar patten was found in each. These results suggest that at least 3 statistically distinct types of age-related influences are operating on a wide variety of cognitive variables and presumably require separate explanatory mechanisms.     

Out of sight,out of mind? Relations between visual acuity and cognition

Prior research has established significant relations between measures of sensory ability and cognitive function in adults of different ages, and several explanations for this relation have been proposed. One explanation is that sensory abilities restrict cognitive processing, a second is that cognitive abilities influence assessments of sensory ability, and a third is that both sensory function and cognition are affected by a common, potentially age-based, third factor. These explanations were investigated using mediation and moderation analyses, with near visual acuity as the sensory measure and scores on visual speed tests and auditory memory tests as the cognitive measures. Measures of visual acuity, speed, and memory were obtained from three moderately large samples, two cross-sectional (N?=?380, N?=?4,779) and one longitudinal (N?=?2,258), with participants ranging from 18 to 90 years of age. The visual acuity and cognitive measures had different age trajectories, and the visual acuity–cognition relations were similar in each 5-year age band. The results suggest that the age-related differences and changes in near visual acuity are unlikely to contribute to the age-related differences and changes in speed and memory measures.     

Aging Effects on Recollection and Familiarity: The Role of White Matter Hyperintensities

ABSTRACT

Previous studies have indicated that aging is associated with declines in recollection whereas familiarity-based recognition is left largely unaffected. The brain changes underlying these recollection declines are yet not well understood. In the current study we examined the role of white matter integrity as measured by white matter hyperintensities (WMH) on age-related changes in recollection and familiarity. Recognition was measured using a remember/know procedure (Experiment 1) and a source-memory process-dissociation procedure (Experiment 2). Robust age related declines in recollection were observed, but there was no evidence that white matter damage was related to the observed memory declines. Although future studies with larger samples will be necessary to fully characterize the role of WMH in normal age-related declines in different types of memory, the results suggest that declines in recollection are not strongly related to the brain changes indexed by WMHs.     

DEVELOPMENTAL SEX DIFFERENCES IN THE RELATION OF NEUROANATOMICAL CONNECTIVITY TO INTELLIGENCE

Recent neuroimaging research has shown sex-related differences in the relationship between brain structure and cognitive function. Anatomical studies have shown a greater reliance for cognitive function on white matter structure in adult females, and a greater reliance on gray matter structure in adult males. Functional neuroimaging studies have also shown a greater correlation between brain connectivity and cognitive function in females. However, this relationship is not present in young childhood (5 years old) but appears during the developmental period. Here sex differences in structure–function relationships and their developmental trajectory are investigated using diffusion tensor imaging (DTI) on a large cohort of over 100 normal children ages 5–18. Significant sex–X–IQ interactions on fractional anisotropy (FA), a marker for white matter organization, were seen in the left frontal lobe, in fronto-parietal areas bilaterally, and in the arcuate fasciculus bilaterally, with girls showing positive correlations of FA with IQ, and boys showing a negative correlation. Significant sex–X–IQ–X–age interactions on FA were also seen in the left frontal lobe and in fronto-parietal areas bilaterally, showing a developmental effect. These results strongly corroborate previous findings regarding sex differences in structure–function relationships regarding intelligence. Results also indicate that a naïve interpretation of “more is better” with respect to FA may not be accurate, especially in adult males.     

Correlation between gray/white matter volume and cognition in healthy elderly people

This study applied volumetric analysis and voxel-based morphometry (VBM) of brain magnetic resonance (MR) images to assess whether correlations exist between global and regional gray/white matter volume and the cognitive functions of semantic memory and short-term memory, which are relatively well preserved with aging, using MR image data from 109 community-dwelling healthy elderly individuals. We used the Information and Digit Span subtests of the Wechsler Adult Intelligent Scale-Revised as measures of semantic memory and short-term memory, respectively. We found significant positive correlations between the gray matter ratio, the percentage of gray matter volume in the intracranial volume, and performance on the Digit Span subtest, and between the regional gray matter volumes of the bilateral anterior temporal lobes and performance on the Information subtest. No significant correlations between performance on the cognitive tests and white matter volume were found. Our results suggest that individual variability in specific cognitive functions that are relatively well preserved with aging is accounted for by the variability of gray matter volume in healthy elderly subjects.     

A cognitive complexity metric applied to cognitive development

Two experiments tested predictions from a theory in which processing load depends on relational complexity (RC), the number of variables related in a single decision. Tasks from six domains (transitivity, hierarchical classification, class inclusion, cardinality, relative-clause sentence comprehension, and hypothesis testing) were administered to children aged 3-8 years. Complexity analyses indicated that the domains entailed ternary relations (three variables). Simpler binary-relation (two variables) items were included for each domain. Thus RC was manipulated with other factors tightly controlled. Results indicated that (i) ternary-relation items were more difficult than comparable binary-relation items, (ii) the RC manipulation was sensitive to age-related changes, (iii) ternary relations were processed at a median age of 5 years, (iv) cross-task correlations were positive, with all tasks loading on a single factor (RC), (v) RC factor scores accounted for 80% (88%) of age-related variance in fluid intelligence (compositionality of sets), (vi) binary- and ternary-relation items formed separate complexity classes, and (vii) the RC approach to defining cognitive complexity is applicable to different content domains.     

The role of sensory factors in cognitive aging research.

Performance on complex, cognitive tasks often is sensitive to low-level sensory and perceptual factors. These relations are particularly important for cognitive aging researchers because aging is associated with a variety of changes in sensory and perceptual function. In the article that follows, I first selectively outline some relations between task performance and sensory function. Next, I summarize age-related changes in visual function and the implications of these changes for task performance, using the digit-symbol subtest of the WAIS as an example. I offer some reasons why age-related sensory decline may not be important to all cognitive tasks. Finally, I provide several recommendations for cognitive gerontologists who want to minimize the risk that the age differences they observe are sensory in nature.     

Correlated and coupled cognitive change in older adults with and without preclinical dementia

Common factor aging theories state that correlations among cognitive age effects signify a single underlying causal process. The logic underlying this proposition was evaluated by examining correlated cognitive change in a sample of 391 initially nondemented older adults who were tested annually for up to 16 years. Between-person correlations among rates of change (range = .56-.61) were partly attributable to model misspecification and the aggregation of heterogeneous groups of individuals. Correlated within-person cognitive change was much stronger in the cases (.45-.51) than in the noncases (.07-.18). These results demonstrate that correlated change may either signify causal commonality or the cumulative effects of multiple age-related conditions that can affect multiple cognitive systems.     

Executive functioning as a potential mediator of age-related cognitive decline in normal adults

Critical requirements for the hypothesis that executive functioning is a potential mediator of age-related effects on cognitive functioning are that variables assumed to reflect executive functioning represent a distinct construct and that age-related effects on other types of cognitive functioning are reduced when measures of executive functioning are statistically controlled. These issues were investigated in a study involving 261 adults between 18 and 84 years of age. Although age-related effects on various cognitive abilities were substantially reduced after statistical control of the variance in measures hypothesized to represent executive functioning, there was only weak evidence for the existence of distinct constructs corresponding to executive functioning or to aspects of executive control concerned with inhibition, updating, or time sharing.     

Global and domain-specific changes in cognition throughout adulthood

Normative adult age-related decrements are well documented for many diverse forms of effortful cognitive processing. However, it is currently unclear whether each of these decrements reflects a distinct and independent developmental phenomenon, or, in part, a more global phenomenon. A number of studies have recently been published that show moderate to large magnitudes of positive relations among individual differences in rates of changes in different cognitive variables during adulthood. This suggests that a small number of common dimensions or even a single common dimension may underlie substantial proportions of individual differences in aging-related cognitive declines. This possibility was directly examined using data from 1,281 adults 18-95 years of age who were followed longitudinally over up to 7 years on 12 different measures of effortful processing. Multivariate growth curve models were applied to examine the dimensionality of individual differences in longitudinal changes. Results supported a hierarchical structure of aging-related changes, with an average of 39% of individual differences in change in a given variable attributable to global (domain-general) developmental processes, 33% attributable to domain-specific developmental processes (abstract reasoning, spatial visualization, episodic memory, and processing speed), and 28% attributable to test-specific developmental processes. Although it is often assumed that systematic and pervasive sources of cognitive decline only emerge in later adulthood, domain-general influences on change were apparent for younger (18-49 years), middle aged (50-69 years), and older (70-95 years) adults.     

第二语言学习与脑可塑性

脑可塑性指人脑会因为环境刺激、认知需求和行为经验而产生功能或结构改变。近10年来的单双语者对比和语言训练研究结果表明, 不论儿童、青年或老年人, 第二语言学习和使用都能改变其脑运行模式并带来相应结构变化, 包括灰质(GM)体积和白质(WM)密度增加, 且长期持续的双语经验还能形成认知优势, 帮助抵制由老化导致的负面认知影响。基于脑可塑性概念及其研究证据, 从双语经验与语言训练两方面, 对比分析了长期和短期第二语言学习引起脑功能或结构变化及其内在机制, 并对未来相关研究进行了展望。