Enhancing brain and cognitive function of older adults through fitness training

The present article provides a brief review of the human and animal literature that has investigated the relationship between fitness training and brain and cognitive function. The animal research clearly suggests that improvements in fitness can lead to both morphological and functional changes in the brains of older animals. Results of a recent meta-analysis suggest that fitness training can also have beneficial effects on human cognition, particularly on tasks requiring executive control processing. These effects are also moderated by a number of factors, including the proportion of men and women in the intervention studies, the length of training sessions, the age of the participants, and the combination of fitness training regimes. The article also discusses preliminary results that link, for the first time, fitness training and differences in human brain structure and function. Finally, we discuss the important issue of participant adherence to fitness training programs and the factors that influence fitness participation.     

Cardiovascular fitness and neurocognitive function in older adults: a brief review

We provide a brief review of the extant research on the influence of cardiovascular fitness training on brain and cognition. The review includes an examination of the non-human animal literature that has reported molecular, cellular, and behavioral consequences of fitness interventions. We relate this literature to human studies of the relationship between fitness and cognition, as well as the nascent literature on fitness influences on human brain structure and function with state-of-the art neuroimaging techniques. We also consider the important topic of participant adherence in clinical exercise trials. Finally, we suggest future directions for studies of cardiovascular fitness, aging, and neurocognitive function.     

Aerobic fitness relates to learning on a virtual Morris Water Task and hippocampal volume in adolescents

In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence--a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory.     

Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training

Cognitive impairment is a prevalent, disabling, and poorly managed consequence of multiple sclerosis (MS). This underscores the importance of considering alternative approaches, such as exercise training, for managing cognitive impairment in persons with MS. The consideration of exercise training is warranted based on evidence summarized in literature reviews and meta-analyses that (1) aerobic fitness, physical activity, and exercise training are associated with better cognitive function in older adults; and (2) exercise training has comparable effects on mobility and quality of life outcomes in older adults and persons with MS. To date, research examining aerobic fitness, physical activity, and exercise training effects on cognition in MS is nascent and mostly includes cross-sectional designs that provide preliminary evidence for a well-designed randomized controlled trial (RCT). We believe that a future RCT should adopt research methodologies and practices from gerontology when examining exercise training and cognition in MS. This will maximize the potential for successfully generating a body of knowledge on exercise training and cognition with the potential for impacting the lives of persons with MS.     

A review of the relation of aerobic fitness and physical activity to brain structure and function in children

A growing number of schools have increasingly de-emphasized the importance of providing physical activity opportunities during the school day, despite emerging research that illustrates the deleterious relationship between low levels of aerobic fitness and neurocognition in children. Accordingly, a brief review of studies that link fitness-related differences in brain structure and brain function to cognitive abilities is provided herein. Overall, the extant literature suggests that childhood aerobic fitness is associated with higher levels of cognition and differences in regional brain structure and function. Indeed, it has recently been found that aerobic fitness level even predicts cognition over time. Given the paucity of work in this area, several avenues for future investigations are also highlighted.     

A review of lateralization of spatial functioning in nonhuman primates

The majority of research on functional cerebral lateralization in primates revolves around vocal abilities, addressing the evolutionary origin of the human language faculty and its predominance in the left hemisphere of the brain. Right hemisphere specialization in spatial cognition is commonly reported in humans. This functional asymmetry is especially evident in the context of the unilateral neglect, a deficit in attention to and awareness of one side of space, that more frequently occurs after right-side rather than left-side brain damage. Since most of the research efforts are concentrated on vocalization in primates, much less is known about the presence or absence of spatial functions lateralization. Obtaining this knowledge can provide insight into the evolutionary aspect of the functionally lateralized brain of Homo sapiens and deliver refinement and validation of the nonhuman primate unilateral neglect model. This paper reviews the literature on functional brain asymmetries in processing spatial information, limiting the search to nonhuman primates, and concludes there is no clear evidence that monkeys process spatial information with different efficiency in the two hemispheres. We suggest that lateralization of spatial cognition in humans represents a relatively new feature on the evolutionary time scale, possibly developed as a by-product of the left hemisphere intrusion of language competence. Further, we argue that the monkey model of hemispatial neglect requires reconsideration.     

Guiding research and practice: a conceptual model for aerobic exercise training in Alzheimer's disease

Alzheimer's disease is a global, epidemic problem affecting mainly older adults with tremendous social and financial burdens. Older adults with Alzheimer's disease showed reduced physical activity and cognitive changes that are probably amenable to aerobic exercise training. The purpose of this paper is to develop a conceptual model to guide future aerobic exercise research and practice by synthesizing the current state of the science on aerobic exercise training in older adults with AD. The literature review found 12 qualified studies that met the eligibility criteria for inclusion in this review and revealed six constructs (aerobic exercise training, physical fitness, physical performance, activities of daily living limitations, cognition, and psychological and behavioral symptoms), which composed the Functional Impact of aerobic exercise Training in Alzheimer's disease (FIT-AD) model. The state of science on each construct in older adults with Alzheimer's disease is reviewed and summarized. The emerging evidence suggests that aerobic exercise training might positively impacts all five other constructs. The implications of the FIT-AD model for future research and practice are discussed highlighted.     

Clinical implications of a link between fetal alcohol spectrum disorder and attention-deficit hyperactivity disorder.

OBJECTIVE: To provide an overview of the animal and human research literature on the link between fetal alcohol spectrum disorder (FASD) and attention-deficit hyperactivity disorder (ADHD). METHOD: We conducted a comprehensive literature review that addressed the history of, and current research on, fetal alcohol syndrome (FAS) and FASD, as well as that on ADHD in children. RESULTS: In animal and human research, there is emerging clinical, neuropsychological, and neurochemical evidence of a link between FASD and ADHD. CONCLUSIONS: The evidence of the link between these 2 conditions has implications for clinical management. The clinical quality of ADHD in children with FASD often differs from that of children without FASD. For children with FASD, ADHD is more likely to be the earlier-onset, inattention subtype, with comorbid developmental, psychiatric, and medical conditions. Children with FASD are commonly not mentally retarded but present complex learning disabilities, especially a mixed receptive-expressive language disorder with deficits in social cognition and communication (reminiscent of sensory aphasia and apraxia), working memory problems, and frequently, a mathematics disorder. Comorbid psychiatric conditions include anxiety, mood, conduct, or explosive disorders. As well, cardiac, renal, or skeletal problems are more likely to be present. Because these children have a disturbance in brain neurochemistry, or even brain structure (that is, in the corpus callosum), their response to standard psychostimulant medication can be quite unpredictable.     

Introduction: ecology and the central nervous system

Behavioral ecology, the study of the survival value or function of behavior, has developed for a time by confining cognition to convenient black boxes that were assumed to be rigged by natural selection to direct an animal to the right decision for a given set of circumstances. However, the interpretation of test results concerning functional hypotheses about behavior depends crucially on assumptions made about their ability to collect and process information: cognition. Clearly, progress in behavioral ecology requires that the cognitive black boxes be opened and studied. This need coincides with an explosive growth of interest in animal cognition that has promoted and enhanced the level of interaction between behavioral ecologists and animal cognition scientists. The result promises to be profitable to the extent that it will raise interest and research in a number of new areas such as the costs in terms of survival value of evolving increased cognitive capacity or even the possibility of exploring brain morphology using a functional approach.     

Hormonal contraceptives and the brain: A systematic review on 60 years of neuroimaging,EEG, and biochemical studies in humans and animals

Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.     

Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature

Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.     

The development of social cognition in adolescence: An integrated perspective

Social cognitive processes are critical in navigating complex social interactions and are associated with a network of brain areas termed the ‘social brain’. Here, we describe the development of social cognition, and the structural and functional changes in the social brain during adolescence, a period of life characterised by extensive changes in social behaviour and environments. Neuroimaging and behavioural studies have demonstrated that the social brain and social cognition undergo significant development in human adolescence. Development of social cognition and the social brain are discussed in the context of developments in other neural systems, such as those implicated in motivational-affective and cognitive control processes. Successful transition to adulthood requires the rapid refinement and integration of these processes and many adolescent-typical behaviours, such as peer influence and sensitivity to social exclusion, involve dynamic interactions between these systems. Considering these interactions, and how they vary between individuals and across development, could increase our understanding of adolescent brain and behavioural development.     

Ovarian hormones,sleep and cognition across the adult female lifespan: An integrated perspective

Loss of ovarian function in women is associated with sleep disturbances and cognitive decline, which suggest a key role for estrogens and/or progestins in modulating these symptoms. The effects of ovarian hormones on sleep and cognitive processes have been studied in separate research fields that seldom intersect. However, sleep has a considerable impact on cognitive function. Given the tight connections between sleep and cognition, ovarian hormones may influence selective aspects of cognition indirectly, via the modulation of sleep. In support of this hypothesis, a growing body of evidence indicates that the development of sleep disorders following menopause contributes to accelerated cognitive decline and dementia in older women. This paper draws from both the animal and human literature to present an integrated view of the effects of ovarian hormones on sleep and cognition across the adult female lifespan.     

A review of cognitive training in schizophrenia

Empirically supported treatments for schizophrenia now include a variety of psychosocial interventions, such as social skills training, vocational rehabilitation, and psychotherapy. As awareness of the functional importance of neurocognitive impairments in schizophrenia has increased, interest in treatments to improve cognition has grown. We review the literature on cognitive training (CT), which has been studied in 17 published randomized, controlled trials to date. The differential effectiveness of noncomputerized and computer-assisted interventions, with and without strategy coaching, and an environmental adaptation intervention, is examined. We conclude that the different types of approaches, whether computer assisted or not, all have effective components that hold promise for improving cognitive performance, symptoms, and everyday functioning. Our recommendations for further research, including the use of functional outcome measures and long-term followup, highlight the importance of improving ecological validity in this area of treatment research.     

Neuroimaging,Gut Peptides and Obesity: Novel Studies of the Neurobiology of Appetite

Two major biological players in the regulation of body weight are the gut and the brain. Peptides released from the gut convey information about energy needs to areas of the brain involved in homeostatic control of food intake. There is emerging evidence that human food intake is also under the control of cortical and subcortical areas related to reward and cognition. The extent to which gut hormones influence these brain areas is not fully understood. Novel methods combining the study of neural activity and hormonal signalling promise to advance our understanding of gut–brain interactions. Here, we review a growing number of animal and human studies using neuroimaging methods (functional magnetic resonance imaging, positron emission tomography) to measure brain activation in relation to nutrient loads and infusion of gut peptides. Implications for current and future pharmacological treatments for obesity are discussed.     

Seizures and Antiepileptic Drugs: Does Exposure Alter Normal Brain Development?

Seizures and antiepileptic drugs (AEDs) affect brain development and have long-term neurological consequences. The specific molecular and cellular changes, the precise timing of their influence during brain development, and the full extent of the long-term consequences of seizures and AEDs exposure have not been established. This review critically assesses both the basic and clinical science literature on the effects of seizures and AEDs on the developing brain and finds that evidence exists to support the hypothesis that both seizures and antiepileptic drugs influence a variety of biological process, at specific times during development, which alter long-term cognition and epilepsy susceptibility. More research, both clinical and experimental, is needed before changes in current clinical practice, based on the scientific data, can be recommended.     

Oral contraceptives and cognition: A systematic review

Oral contraceptives (OCs) are widely used. While the physical impacts of OCs have been well researched, there is increasing interest on potential impacts of OCs on brain, behaviour and cognition. We systematically reviewed the literature to determine the influence of OCs on cognition, including neurocognition, social cognition and emotional processing. Inclusionary criteria were: (a) premenopausal females taking OCs; (b) a control group of naturally cycling women or OCs users in their inactive (i.e. ‘sugar pill’) phase; and (c) at least one measure of performance on a neurocognitive or social cognitive task. The systematic review found that OC use was associated with some differences in performance on all cognitive domains examined (with the exception of basic auditory attention and psychomotor performance). Several factors were identified that are likely to modulate the way OCs influence cognition, including task related factors, OC type and control group characteristics. Directions for future research are highlighted.     

When Top-Down Meets Bottom-Up: Auditory Training Enhances Verbal Memory in Schizophrenia

A critical research priority for our field is to develop treatments that enhance cognitive functioning in schizophrenia and thereby attenuate the functional losses associated with the illness. In this article, we describe such a treatment method that is grounded in emerging research on the widespread sensory processing impairments of schizophrenia, as described elsewhere in this special issue. We first present the rationale for this treatment approach, which consists of cognitive training exercises that make use of principles derived from the past 2 decades of basic science research in learning-induced neuroplasticity; these exercises explicitly target not only the higher order or “top-down” processes of cognition but also the content building blocks of accurate and efficient sensory representations to simultaneously achieve “bottom-up” remediation. We then summarize our experience to date and briefly review our behavioral and serum biomarker findings from a randomized controlled trial of this method in outpatients with long-term symptoms of schizophrenia. Finally, we present promising early psychophysiological evidence that supports the hypothesis that this cognitive training method induces changes in aspects of impaired bottom-up sensory processing in schizophrenia. We conclude with the observation that neuroplasticity-based cognitive training brings patients closer to physiological patterns seen in healthy participants, suggesting that it changes the brain in an adaptive manner in schizophrenia.     

Starving the brain: structural abnormalities and cognitive impairment in adolescents with anorexia nervosa

Anorexia nervosa (AN) is one of the most common chronic illnesses afflicting adolescent girls and is associated severe medical complications. The structural abnormalities found in the brain of adolescents with AN are among the earliest and most striking physical consequences. In the past, it had been assumed that the brain abnormalities found in patients with AN reverse with weight-recovery. Recent evidence has shown that not all of these changes are completely reversible with weight recovery. To date, very little is known about the functional significance of these brain abnormalities. Several studies have shown that cognitive dysfunction is also a common feature of AN. Although current evidence suggests that there may be some degree of improvement in cognition with weight-recovery, it is unclear whether cognition recovers fully or equally across all neuropsychological domains. Furthermore, it remains unknown whether the reported functional consequences are associated with these structural brain changes. This article will review the current literature on structural brain abnormalities and cognitive dysfunction in adolescents with AN.     

Examining the Relationship Between Neurosteroids,Cognition, and Menopause With Neuroimaging Methods

Purpose of Review

Previous literature has shown inconsistent findings regarding the effects of neurosteroids on the brain in postmenopausal women. The goal of this paper is to examine how and whether advances in neuroimaging have helped elucidate the relationship between the withdrawal of and/or treatment with neurosteroids and cognition at menopause.

Recent Findings

Neuroimaging techniques such as structural and functional MRI have been used in recent studies to examine the relationship between neurosteroids and brain structure and functioning. However, the recent literature shows that different formulations of postmenopausal hormones given at different times, through different routes of administration, and in different combinations with progestins result in a variety of relationships with the brain outcomes.

Summary

We suggest that still further research is needed to understand how the structural changes resulting from estrogen withdrawal or therapy at menopause can influence cognitive functioning. However, imaging studies are time-, resource-, and expertise-intensive. We believe that this information will help uncover the mechanisms and relationships that can aid in the explanation of the individual differences in the effects of menopause on the brain as well as how this menopause-related hormone change influences risk for pathological aging.