Impact on physical fitness on cognitive aging

Cognitive vitality is one of the determining factors of autonomy in the elderly. Aging is often accompanied by important changes in the central nervous system, which may lead to cognitive decline. Several factors seem however to modulate the effect of aging on cognition. For instance, older adults who engage in regular physical activity have better performances in tests implying decision-making process, memory and problems solving. This article draws up a portrait of normal aging while being interested in the impact of the physical fitness on cognition in the elderly. Although further researches are needed to elucidate the mechanisms by which physical fitness enhance cognition in old age, recent studies have shown that improving physical fitness leads to better performances in tasks assessing a diversity of cognitive domains. Moreover, the impact of physical fitness appears to be heterogeneous, being of greater amplitude in tasks that tap executive functions. It thus seems that physical training could serve to enhance and maintain cognitive vitality in older adults.     

Human frontal lobes are not relatively large

One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and of specific frontal regions, is as expected relative to the size of other brain structures. Recent claims for relative enlargement of human frontal white matter volume, and for relative enlargement shared by all great apes, seem to be mistaken. Furthermore, using a recently developed method for detecting shifts in evolutionary rates, we find that the rate of change in relative frontal cortex volume along the phylogenetic branch leading to humans was unremarkable and that other branches showed significantly faster rates of change. Although absolute and proportional frontal region size increased rapidly in humans, this change was tightly correlated with corresponding size increases in other areas and whole brain size, and with decreases in frontal neuron densities. The search for the neural basis of human cognitive uniqueness should therefore focus less on the frontal lobes in isolation and more on distributed neural networks.     

轻度认知障碍患者多模态磁共振特征

目的 探讨轻度认知损害者(MCI)和阿尔茨海默病(AD)患者多模态磁共振成像特征与认知功能的关系.方法 共纳入9例遗忘型MCI,15例轻度AD及11例正常对照,以简明精神状况检查(MMSE)和认知功能筛查测验(CASI)评估总体认知功能,对高分辨率结构像进行基于体素形态学分析(VBM),测量扩散张量成像(DTI)图像、各脑区白质各向异性比值(FA)和平均表观弥散系数(ADC),分析脑结构萎缩及白质DTI指标与认知评分的相关性.结果 MMSE和CASI评分与颞、额、顶、扣带回、海马旁回等结构灰质体积改变呈正相关(P<0.001),MMSE和CASI总分与颞、顶叶以及海马旁回的FA值呈正相关,与ADC值呈负相关(P<0.05).结论 MCI和AD患者认知功能与颞、顶、海马旁回等脑区萎缩及白质微观结构损伤密切相关,多模态影像技术可作为认知损害脑机制研究的重要技术手段.     

Cognitive fitness of cost-efficient brain functional networks

The human brain''s capacity for cognitive function is thought to depend on coordinated activity in sparsely connected, complex networks organized over many scales of space and time. Recent work has demonstrated that human brain networks constructed from neuroimaging data have economical small-world properties that confer high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of complex brain networks functioning at different frequencies can be related to behavioral performance on cognitive tasks. Here, we show that impaired accuracy of working memory could be related to suboptimal cost efficiency of brain functional networks operating in the classical β frequency band, 15–30 Hz. We analyzed brain functional networks derived from magnetoencephalography data recorded during working-memory task performance in 29 healthy volunteers and 28 people with schizophrenia. Networks functioning at higher frequencies had greater global cost efficiency than low-frequency networks in both groups. Superior task performance was positively correlated with global cost efficiency of the β-band network and specifically with cost efficiency of nodes in left lateral parietal and frontal areas. These results are consistent with biophysical models highlighting the importance of β-band oscillations for long-distance functional connections in brain networks and with pathophysiological models of schizophrenia as a dysconnection syndrome. More generally, they echo the saying that “less is more”: The information processing performance of a network can be enhanced by a sparse or low-cost configuration with disproportionately high efficiency.     

Greater Activation in Left Hemisphere Language‐Related Regions During Simple Judgment Tasks Among Substance‐Dependent Patients in Treatment for Alcoholism

Background: Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive‐type tasks. In this study, we compared brain activations of alcohol‐dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods: We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results: There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions: Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision‐making tasks.     

Neural correlates of training-related memory improvement in adulthood and aging

Cognitive studies show that both younger and older adults can increase their memory performance after training in using a visuospatial mnemonic, although age-related memory deficits tend to be magnified rather than reduced after training. Little is known about the changes in functional brain activity that accompany training-induced memory enhancement, and whether age-related activity changes are associated with the size of training-related gains. Here, we demonstrate that younger adults show increased activity during memory encoding in occipito-parietal and frontal brain regions after learning the mnemonic. Older adults did not show increased frontal activity, and only those elderly persons who benefited from the mnemonic showed increased occipito-parietal activity. These findings suggest that age-related differences in cognitive reserve capacity may reflect both a frontal processing deficiency and a posterior production deficiency.     

Selective atrophy of left hemisphere and frontal lobe of the brain in old men

In this study, volumes of the whole brain, hemispheres, and frontal lobes of young and elderly adults were quantified by an automated method. Effects of age, sex, and side on absolute and relative volumes of the brain structures were evaluated. Compared with the young group, elderly participants showed a 15% volume loss in the whole brain and hemispheres, and a 22% volume loss in the frontal lobes. The relative volume of the left hemisphere in the elderly group decreased more than that of the right hemisphere. Elderly men showed significantly greater left hemisphere and left frontal lobe volume losses than did elderly women, indicating that the larger left hemisphere relative volume reduction is largely contributed to by selective atrophy of the left frontal lobe volume in elderly men. These results may reflect age- and sex-related functional deterioration in the left brain.     

Session II: Mechanisms of age-related cognitive change and targets for intervention: neural circuits, networks, and plasticity

Age-related changes in neural circuits, neural networks, and their plasticity are central to our understanding of age changes in cognition and brain structure and function. This paper summarizes selected findings on these topics presented at the Cognitive Aging Summit II. Specific areas discussed were synaptic vulnerability and plasticity, including the role of different types of synaptic spines, and hormonal effects in the dorsolateral prefrontal cortex of nonhuman primates, the impact of both compensatory processes and dedifferentiation on demand-dependent differences in prefrontal activation in relation to age and performance, the role of vascular disease, indexed by white matter signal abnormalities, on prefrontal activation during a functional magnetic resonance imaging-based cognitive control paradigm, and the influence of amyloid-β neuropathology on memory performance in older adults and the networks of brain activity underlying variability in performance. A greater understanding of age-related changes in brain plasticity and neural networks in healthy aging and in the presence of underlying vascular disease or amyloid pathology will be essential to identify new targets for intervention. Moreover, this understanding will assist in promoting the utilization of existing interventions, such as lifestyle and therapeutic modifiers of vascular disease.     

Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography.

Increasing interest in the role of the frontal lobe in relation to psychiatric and neurologic disorders has popularized tests of frontal function. One of these is the antisaccade task, in which both frontal lobe patients and schizophrenics are impaired despite normal performance on (pro)saccadic tasks. We used position emission tomography to examine the cerebral blood flow changes associated with the performance of antisaccades in normal individuals. We found that the areas of the brain that were more active during antisaccades than saccades were highly consistent with the oculomotor circuit, including frontal eye fields (FEFs), supplementary motor area, thalamus, and putamen. Superior parietal lobe and primary visual cortex were also significantly more active. In contrast, prefrontal areas 46 and 9 were not more active during antisaccades than during saccades. Performance of some frontal patients on the antisaccade task has been likened to a bradykinesia, or the inability to initiate a willed movement. It is the necessity to will the movement and inhibit competing responses that intuitively linked this task to the dorsolateral prefrontal cortex in frontal patients. Our data suggest that it is the FEFs in prefrontal cortex that differentiate between conditions in which the required oculomotor response changes while the stimulus remains the same, rather than areas 46 and 9, which, in human studies, have been linked to the performance of complex cognitive tasks. Such a conclusion is consistent with single-unit studies of nonhuman primates that have found that the FEFs, the executive portion of the oculomotor circuit, can trigger, inhibit, and set the target of saccades.     

Premotor functional connectivity predicts impulsivity in juvenile offenders

Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain-behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.     

Exploration of functional brain networks in neurodegenerative disease

Neurodegenerative diseases target specific anatomical and functional brain networks. A number of intrinsic functional brain networks can be identified in individuals at rest, that correspond to networks found in task-based functional MRI studies. However, the impact of pathological changes and relation to disease severity remains unclear.We examined three networks of interest in patients with progressive supranuclear palsy (PSP) and the neurodegenerative corticobasal syndrome (CBS). These two diseases share features of cognitive decline and a movement disorder, although they have important phenotypic differences. They are both associated with accumulation of tau protein in neuronal and glial cells. We examined the default mode network, which is deactivated during tasks and has been consistently implicated in Alzheimer's disease; the salience network, often activated during tasks and affected in frontotemporal dementia; and the basal ganglia network, since both PSP and CBS pathology affects the basal ganglia.Using resting state functional MRI scanning, we applied independent component analysis and template matching to identify networks of interest. Spatiotemporal group differences in network architecture were identified with dual regression to extract spatial maps for each network in individuals and perform group-wise t tests. In addition, clinical test scores were added as covariates to group comparisons.Increased functional connectivity was seen within all three networks in disease groups. Decreased connectivity was seen between the basal ganglia network and cortical regions in PSP. Network changes correlated with worse scores on clinical measures of disease.Increased connectivity in relevant functional brain networks identify neurodegenerative diseases and mirror clinical disease features.FundingUK Medical Research Council.     

Cross-domain variability of cognitive performance in very old nursing home residents and community dwellers: relationship to functional status

BACKGROUND: Recent evidence suggests that cross-domain variability in cognition may be related to subsequent cognitive decline beyond mean performance levels in cognitive tasks. OBJECTIVES: To examine age-related changes in cross-domain variability across cognitive task performance in very old nursing home residents in contrast to community-dwelling older adults. To explore the relationship between cross-domain variability in cognition and functional disability in very old age. METHODS: 204 very old (82.00+/-8.51 years) residents from the Jewish Home and Hospital, Bronx, N.Y., and 376 community-dwelling older adults of similar age (86.75+/-5.84 years) were tested on a cognitive battery. Cross-domain variability scores were computed across the cognitive tasks. Functional disability measures were derived from the CDR (Clinical Dementia Rating) Scale. RESULTS: Whereas oldest old community-dwelling adults showed a decrease in variability across domains with age, variability increased with age in nursing home residents, irrespective of the level of cognitive performance. Cross-domain variability was associated with functional disability beyond the effects of age, gender, education, dementia status, residential status, and level of cognitive performance. CONCLUSION: Findings suggest that cross-domain variability in cognition is related to functional decline with age. Cross-domain variability in cognition may be a prominent predictor for the development of functional decline in very old adults.     

Cognitive reserve and neural networks in normal aging and Alzheimer's disease

Since the 1990s, functional neuroimaging studies on normal and pathological aging showed the involvement of different patterns of activation in comparison with control populations, such as increased frontal activity. These differences have been interpreted as reflecting the implementation of compensatory processes. Confronted to age-related or pathological brain changes, alternative neural networks would be used to perform cognitive tasks. Besides, a rather important variability has been reported in old individuals. This variability concerns not only their cognitive capacities, but also the involvement of different neural pathways according to their performance. This variability could result from differences in cognitive reserve, which can be defined as the capability of an individual to cope with a task in order to optimize his/her performance by the recruitment of different neural networks and/or by using alternative cognitive strategies. The notion of cognitive reserve is very recent and, due to its complexity, is still not well-defined. The main aims of this review are to clarify this notion by summing up the various factors participating in cognitive reserve, to estimate its impact on memory, and to link it with the brain modifications reported in the literature regarding normal aging and Alzheimer's disease. Finally, from a clinical point of view, we suggest to take into account the notion of cognitive reserve during the neuropsychological evaluation of neurodegenerative diseases in the upcoming years.     

Are behaviour and motor performances of rheumatoid arthritis patients influenced by subclinical cognitive impairments? A clinical and neuroimaging study

OBJECTIVE: To determine whether some behavioural manifestations and poor motor performances in patients affected by rheumatoid arthritis (RA) are due to subclinical cognitive defects. METHODS: We performed a psychometric assessment of 30 patients affected by RA exploring several cognitive domains such as memory, visual-spatial integration, motor planning, mental flexibility, relating performances with morphological and functional neuroimaging (MRI and SPECT). We also related the cognitive data with the Ritchie and Lee indexes and other clinical parameters. RESULTS: We found an impairment in visual-spatial tasks in 71% of patients with a high correlation to activity and disease severity as expressed by the Ritchie and Lee indexes (p < 0.005; p < 0.01). Furthermore, we detected in 38% of patients some difficulties in mental flexibility related to the Lee Index (p < 0.05). These poor performances are related to hypoperfusion of the frontal and parietal lobes as detected by brain SPECT; this finding is more evident in patients with brain white matter alterations on MRI. CONCLUSIONS: Our data allow us to hypothesize that manual dexterity could be due to a disconnection between subcortical white matter and parietal-frontal lobes because of microangiopathy; furthermore, a chronic reduction in sensorial stimuli by impaired joints could lead to produce an alteration in motor planning cognitive processes.     

Verb generation in patients with focal frontal lesions: A neuropsychological test of neuroimaging findings

What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal cortex. Has neuroimaging taught us something new about the neural bases of cognition that older methods could not reveal or has it merely identified brain activity that is correlated with but not causally related to the process of semantic retrieval? We examined the ability of patients with focal frontal lesions to perform a task commonly used in neuroimaging experiments, the generation of semantically appropriate action words for concrete nouns, and found evidence of the necessity of the left inferior frontal gyrus for certain components of the verb generation task. Notably, these components did not include semantic retrieval per se.     

Cognitive relevance of the community structure of the human brain functional coactivation network

There is growing interest in the complex topology of human brain functional networks, often measured using resting-state functional MRI (fMRI). Here, we used a meta-analysis of the large primary literature that used fMRI or PET to measure task-related activation (>1,600 studies; 1985–2010). We estimated the similarity (Jaccard index) of the activation patterns across experimental tasks between each pair of 638 brain regions. This continuous coactivation matrix was used to build a weighted graph to characterize network topology. The coactivation network was modular, with occipital, central, and default-mode modules predominantly coactivated by specific cognitive domains (perception, action, and emotion, respectively). It also included a rich club of hub nodes, located in parietal and prefrontal cortex and often connected over long distances, which were coactivated by a diverse range of experimental tasks. Investigating the topological role of edges between a deactivated and an activated node, we found that such competitive interactions were most frequent between nodes in different modules or between an activated rich-club node and a deactivated peripheral node. Many aspects of the coactivation network were convergent with a connectivity network derived from resting state fMRI data (n = 27, healthy volunteers); although the connectivity network was more parsimoniously connected and differed in the anatomical locations of some hubs. We conclude that the community structure of human brain networks is relevant to cognitive function. Deactivations may play a role in flexible reconfiguration of the network according to cognitive demand, varying the integration between modules, and between the periphery and a central rich club.     

Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET)

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.     

fMRI BOLD response to the eyes task in offspring from multiplex alcohol dependence families

Background:  Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain.
Methods:  Adolescent/young adult participants from multiplex AD families and controls ( n  = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI).
Results:  High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks.
Conclusions:  Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.     

血管性痴呆的扩散张量成像研究

目的应用扩散张量成像(DTI)技术,探讨皮质下缺血性血管性痴呆(SIVD)患者脑白质变化的特点及不同脑区DTI参数改变与认知的关系。方法对34例SIVD患者(SIVD组)及26例健康老年人(对照组)行DTI扫描,测量双侧前额叶、额叶深部、眶额内侧、下额叶、颞叶、顶叶、枕叶白质及T_2WI高信号区、T_2WI高信号周围正常白质区的分量各向异性(FA)、主各向异性(PA)及表观弥散系数(ADC)值。结果对照组左侧前额叶白质PA值大于右侧,ADC值小于右侧。SIVD组双侧前额叶、双侧额叶深部、下额叶、眶额内侧的FA值及PA值明显下降,平均ADC值升高;双侧顶叶的FA值下降,平均ADC值升高;双侧颞叶、枕叶平均ADC值升高;左侧下额叶、眶额内侧白质的FA与PA值较右侧小;左侧下额叶ADC值较右侧大。病变区及病变周围区的FA和PA值小于正常区,ADC值大于正常区。前额叶FA与简易智能状态检查表评分呈正相关。结论 SIVD患者脑白质FA、PA和ADC改变具有区域选择性,前部及左侧脑区损伤明显,后部及右侧相对保留白质的完整性。DTI是研究SIVD脑白质损伤的一种理想的方法。     

Clinical validation of the watershed sign as a marker for neuropsychiatric systemic lupus erythematosus

OBJECTIVE: To study the relationship between single-photon-emission computed tomography (SPECT) brain imaging and neuropsychiatric signs/symptoms in a cohort of patients with systemic lupus erythematosus (SLE), analyzed using a stereotactic surface projection (SSP) technique. METHODS: Thirty-seven SLE patients were referred for 99mTc-ethyl cysteinate dimer SPECT brain imaging because of neuropsychiatric signs/symptoms. Nineteen normal controls were studied with the identical protocol. Reconstructed images were computed and Z scores were calculated using the SSP technique with the 2-sample t-tests comparing normal controls with SLE patients, and patients with mild cognitive dysfunction with those with severe cognitive dysfunction. The clinical characteristics of SLE patients were collected by retrospective chart review and categorized according to American College of Rheumatology case definitions for neuropsychiatric SLE. Cognitive dysfunction was rated by the treating physician on a scale of 0-3. RESULTS: Thirty of 37 SLE patients had abnormal SPECT results. SLE patients had reduced perfusion in the watershed areas of the frontal lobes bilaterally compared with controls. Additionally, SLE patients with severe cognitive dysfunction had more severe perfusion deficits than those with mild cognitive dysfunction. In some patients with severe cognitive dysfunction, the watershed areas had Z scores > or =4 SDs below controls. CONCLUSION: A convenience sample of patients with SLE and neuropsychiatric signs/symptoms demonstrated reduced perfusion in the watershed areas of the frontal lobes on SPECT scanning analyzed by the SSP technique. The severity of findings correlated with severity of cognitive dysfunction. The area of the brain affected is one that is susceptible to ischemia.