The contribution of functional brain imaging to our understanding of cognitive aging

The study of cognitive aging seeks to determine the psychological and neural mechanisms underlying age-related decline in cognitive performance. New methods in functional brain imaging are beginning to provide possible answers to questions regarding age-related cognitive decline.     

Ubiquitin,proteasomes, and the aging brain

Ubiquitinated proteinaceous inclusions are the hallmark of many neurodegenerative diseases. Inefficient proteolysis might lead to the accumulation and ultimate deposition of potentially toxic entities as inclusions within neurons or glial cells. This hypothesis is supported by genetic evidence both from patient populations and from engineered mutations in genes that encode ubiquitin/proteasome components in mice. The appearance of similar inclusions in the brains of elderly individuals of normal and subclinical conditions begs the question of whether there is a general age-related decline in the ability of the ubiquitin/proteasome pathway (UPP) to recognize and eliminate abnormal proteins, and whether such a decline would be reflected by changes in the abundance or activity of some or all components of the UPP. Here we describe alterations in the aging mammalian brain that correlate with a decline in the function of the UPP and review the evidence for age-related changes in specific UPP components. These alterations are discussed within the context of prevalent theories of aging.     

Cognitive,social, and neural determinants of diminished decision-making and financial exploitation risk in aging and dementia: A review and new model

ABSTRACT

In this article we will briefly review how changes in brain and in cognitive and social functioning, across the spectrum from normal to pathological aging, can lead to decision-making impairments that increase abuse risk in many life domains (e.g., health care, social engagement, financial management). The review will specifically focus on emerging research identifying neural, cognitive, and social markers of declining financial decision-making capacity in older adults. We will highlight how these findings are opening avenues for early detection and new interventions to reduce exploitation risk.     

Gonadal steroids and visuo-spatial abilities in adult males: Implications for generalized age-related cognitive decline

The relationship between the gonadal steroids, testosterone and estrogen, and individual and group differences in performance on some cognitive tasks remains unclear but sex differences favoring males on some tests of visuo-spatial ability are large and robust. This aim of this review is to assess evidence for both organizational and activational effects of gonadal steroids as the principle cause of sex difference in visuo-spatial ability. Additionally, the implications of this relationship are discussed in the context of decreasing levels of gonadal steroids in aging males and psychological theories of generalized age-related cognitive decline. Based upon human and non-human research gonadal steroids have organizational effects on visuo-spatial ability in adulthood. Activational effects of gonadal steroids on visuo-spatial ability appear most dominant in older men and are necessary for maintaining optimal visuo-spatial ability; randomized clinical trials show that testosterone supplementation improves performance. Additionally, decreasing gonadal steroid levels in aging males may contribute to generalized age-related cognitive decline. Future supplementation studies in men should attempt to control for constituent abilities related to visuo-spatial task performance, and investigate interactions between dosage levels and baseline gonadal status. Further future animal research is required to investigate changes in gonadal steroid levels and their relationship to neurotransmitter systems, neural plasticity, and behavioral correlates.     

A life course approach: research orientations and future challenges

The need to study lifelong changes in health and functioning has resulted in increasing emphasis on a life course approach in different fields of inquiry. The aim of this approach is to explore how biological, psychological, and social risk factor trajectories, acting across the entire life course, influence age-related diseases, functional decline, and disability. The importance of the first years of life upon later development and adult characteristics was generally recognized already in the first half of the twentieth century, but it was not until the 1990s that different strands of medical and social research converge in the field of life course epidemiology, in which epidemiological processes are approached using different models such as biological programming, critical periods, pathways, and accumulation. The biological programming model holds that organ development in utero and early infancy determines the maximum functional capacity that an individual can attain and influences the development of certain chronic diseases later in life. The critical period model extends the idea to include child development and key social transitions over the entire life course. The pathway model focuses on the cumulative effect of life events along the developmental trajectories, with early advantage or disadvantage setting a person on a pathway to a later etiologically important exposure. The accumulation model describes the underlying social, behavioral, and biological processes that drive the impact of the life course on health. The growing focus on life course determinants of aging also has implications for studies of long-term changes in physical activity and their role in determining both gains and losses of health and functioning with aging. A life course approach presents great challenges for the continued development of testable theoretical models and effective study design and analysis.     

The effects of physical activity and sedentary behavior on cognitive health in older adults

Physical activity has been shown to be positively associated with cognitive health, but the mechanisms underlying the benefits of physical activity on cognitive health are unclear. The present study simultaneously examined two hypotheses using structural equation modeling (SEM). The depression-reduction hypothesis states that depression suppresses cognitive ability and that physical activity alleviates dysphoric mood and thereby improves cognitive ability. The social-stimulation hypothesis posits that social contact, which is often facilitated by socially laden physical activities, improves cognitive functioning by stimulating the nervous system. Sedentary behavior in the absence of physical activity is expected to exert an inverse relationship on cognitive health through each of these hypotheses. Community-dwelling elders (N = 158) were administered a variety of measures of cognition, depression, social support, and physical activity. SEM techniques provided partial support for the social-stimulation hypothesis and depression-reduction hypothesis. Implications for treating depression and improving cognitive functioning are discussed.     

Predictors of falling in older Maryland drivers: a structural-equation model

Falls can impair health and reduce quality of life among older adults. Although many factors are related to falling, few analyses examine causal models of this behavior. In this study, factors associated with falling were explored simultaneously using structural-equation modeling. A variety of cognitive, physical-performance, and health measures were administered to 694 older adult drivers from the state of Maryland. The observed and latent variables of age, cognitive ability, physical functioning, health, and falling behavior were used to create a causal model. The model revealed that being older was associated with declines in cognition, and such cognitive declines predicted increased falling. Similarly, poorer health was related to poorer physical functioning, which, in turn, also predicted increased falling. This model indicates that in addition to existing fall-prevention interventions aimed at improving physical functioning, interventions to improve cognition and health might also be effective. It is speculated that fear of falling, which often results in reduced mobility among older adults, might account for the lack of a direct relationship between age and falling. This hypothesis should be examined in further research.     

An examination of the mechanisms underlying the effects of physical activity on brain and cognition

Physical activity positively influences brain health and cognitive functioning in older adults. Several physiological and psychological mechanisms have been identified to underlie such a relationship. Cardiovascular fitness is accompanied with changes in mechanisms such as cerebral blood flow, neurotrophic factors, neurotransmitter systems and neural architecture that have themselves been associated with cognitive performance. Factors associated with exercise such as arousal, mood and self-perception of competence seem also to influence cognitive performance. Other explanation for the benefits of exercise in cognition, results from the fact that the performance of motor skills involve an important cognitive component (e.g., executive functions and information processing speed). Evidence of brain plasticity and behavior has been provided from studies where animals are exposed to enriched or complex environments. Exposure to such paradigms in which physical activity plays an important role has been found to influence various aspects of brain function and structure. Studies using neuroimaging techniques have established a link between the acquisition of different motor skills and the occurrence of neuroplasticity in human adults. This literature review indicates that the type of exercise and its specific perceptual and cognitive characteristics may influence cognitive performance. However, most of the research has been focused on self-paced movements or automatized skills and few intervention studies have examined the results of merging exercise and cognitive training in a single program. An important scientific challenge for the coming years is to design exercise programs capable of mobilizing several type of mechanisms underlying the effects of physical activity on brain and cognition.     

Does physical exercise improve perceptual skills and visuospatial attention in older adults? A review

Neuroimaging studies suggest that when the brain ages, more areas are involved to perform a task in order to obtain the same results. This, together with the increase in crystalized intelligence and wisdom, is usually considered as a compensatory strategy. Research has demonstrated that physical activity might also act as a strategy and be one of the main factors that can slow down age-related perceptual and cognitive decline. Research also suggests that different types of physical exercise and sport lead to different changes in perceptual and cognitive skills as well as in several areas of the brain, especially those involving multiple domains, such as exergaming, dance or some sports. This review summarizes the findings of recent studies with older adults investigating the brain and cognitive benefits of different forms of physical exercise. Visuospatial attention, which plays a critical role in our daily lives, especially for older adults, is a central part of this analysis.     

Expertise and aging: maintaining skills through the lifespan

As lifespan continues to increase in many developed countries, so too does the age at which we see extraordinary achievements from older adults. Examples from running, golf, and other domains continue to redefine what is possible as we age. Evidence suggests, however, that progression through adulthood is associated with a dramatic decline in all manner of physical and cognitive abilities, from physiological capacities (e.g., VO2 max) to cognitive and perceptual functions (e.g., IQ scores, reaction time). In the face of such precipitous decline in specific abilities, how do we account for maintenance of skilled performance and expertise amongst those supposedly well along the age-decline curve? Expert performers are seemingly able to sustain high levels of achievement in the face of an overall deterioration in general capacities. Moreover, experts maintain this performance in spite of reduced involvement in their field. There are three primary explanations for the ability of experts to maintain superior performance in spite of an overall decline in abilities: (a) preserved differentiation, (b) compensation, and (c) selective maintenance. Overall, research into the high achievements of older adults may reveal a great deal with respect to skill preservation and how to best counter age-related decline.     

Sexual expression in later life: a review and synthesis

In the past decade, researchers have begun to study the sexual functioning of typical older persons. This review summarizes literature on the sexuality of men and women over age 50 as researched by social and health scientists. Research on the relationship of biological factors (changes accompanying aging), health (physical, mental, and medication use), psychological factors (attitudes, information about sex), relationship factors (status, satisfaction), and sexual functioning (desire, dysfunctions, treatment) to sexual behavior is reviewed. The review suggests that (a) men and women remain sexually active into their 70s and 80s, (b) aging-related physical changes do not necessarily lead to decline in sexual functioning, and (c) good physical and mental health, positive attitudes toward sex in later life, and access to a healthy partner are associated with continued sexual activity. In turn, regular sexual expression is associated with good physical and mental health. Progress in understanding later life sexuality requires development of comprehensive theoretical models, a broad focus on intimacy, attention to measures and samples, and research on couples. Progress in understanding is especially important, given the aging of populations.     

Age-related slowing of movement as basal ganglia dysfunction

Attributions of age-related deficits in motor function to structural changes are compromised once the elderly exhibit lower error rates. This is because performance decrements observed in older adults are attributed to inferred strategic preferences for accuracy over speed. To understand genuine age differences in performance, we argue in the following theoretical paper that research needs to resolve methodological shortcomings and account for them within theoretical models of aging. Accounts of aging need to directly manipulate or control strategic differences in performance while assessing structural deficits. When this is done, age-related changes in motor control resemble the intermittencies of control seen in basal ganglia disorders. Given homologous circuitry in the basal ganglia, such observations could generalize to age-related changes in cognitive and emotional processes.     

Testosterone is associated with age-related changes in bone health status,muscle strength and body composition in men

Objective: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass. Materials and methods: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging. Results: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05). Conclusion: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.     

The relevance of situation awareness in older adults’ cognitive functioning: a review

Age-related declines in cognition may have detrimental effects on older adults’ ability to complete everyday activities that young- and middle-aged individuals perform automatically. Theories of cognitive aging have found deficits in older adults’ fluid intelligence, capacity for inhibition, number of processing resources, and speed of processing, and in recent years, studies have proposed cognitive strategies to ameliorate these declines. However, few strategies directly train the cognitive strategies necessary to improve performance in dynamic environments and physical activities. One such strategy may be the enhancement of situation awareness, the capability to perceive and understand one’s environment. Although the term has typically been applied to pilots and other expert performers, situation awareness may also be relevant to cognitive aging, where older adults’ perception and comprehension of their environment become critical to everyday functioning and physical activities. If older adults’ situation awareness can be facilitated, then it may be possible to reduce the impact of age-related cognitive declines, allowing older adults to successfully participate in dynamic situations and sports where the environment is constantly changing (e.g., driving and tennis). The following review outlines cognitive deficits in aging, details their relation to situation awareness, and discusses how training in situation awareness may reduce cognitive declines. Portions of this paper were reported at the annual meeting of the North American Society for the Psychology of Sport and Physical Activity in June, 2005.     

Olfactory loss in aging

Olfactory loss is a common age-related complaint that may be caused by changes in the anatomy of the structures required for olfaction (for example, loss of olfactory receptor cells) or in the environment surrounding the receptor cell (for example, altered nasal mucus composition). However, aging, as well as age-related diseases and medications, may also alter the distribution, density, or function of specific receptor proteins, ion channels, or signaling molecules that affect the ability of neural elements throughout the olfactory pathway to signal and process odorant information. Although a great deal has been learned about the prevalence and nature of age-related olfactory loss, we are just beginning to explore avenues to prevent or alleviate this sensory deficit. Some studies suggest that, rather than being a necessary outcome of aging, age-associated factors such as chronic diseases, medications, and dental and sinus problems are the primary culprits in causing olfactory impairment. This idea suggests optimism in that, as we address these other age-related health issues, the prevalence of olfactory loss will lessen as well.     

Keeping priorities: the role of working memory and selective attention in cognitive aging

Cognitive aging is associated with impairments to working memory and top-down control in selective attention, two components of cognitive control associated with the frontal lobes. Recent findings indicate that working memory and selective attention may be interdependent, making a better understanding of their involvement in cognitive aging particularly challenging. A paper in a recent issue of Nature Neuroscience has provided evidence that a reduction in the ability to keep a clear distinction between information to be stored in working memory and information that should be ignored and subsequently suppressed is associated with poor working memory performance. These results are in line with previous evidence for a specific age-related impairment in the ability to separate irrelevant from relevant information and may be able to explain a range of age-related cognitive changes.     

Successful aging: how does physical activity influence engagement with life?

With the increasing number of individuals over the age of 65?years worldwide, it is critical for society to recognize the importance of helping seniors maintain their health, physical, and cognitive functioning as well as their engagement with life. These three dimensions provide the foundation for successful aging (SA). The positive role of engagement with life has been understated to date in the literature. This review highlights the components of SA with particular emphasis on engagement and how physical activity positively impacts engagement which in turn positively influences health and physical function.     

Aging-related temporal constraints to stability and instability in postural control

In this study, we review the evidence that older adults tend to have both a shorter time to lose stability in the maintenance of standing posture and the functionally related but inverse problem of needing more time to reacquire stability in transitioning to a postural state. These age-related time limitations to processes of stability are hypothesized to enhance the probability of falling with aging and the problems that can occur in the transition between activities, such as sitting to standing and standing to walking. The potential role of fitness and health variables in mediating the temporal constraints on the acquisition and loss of postural stability in aging is discussed.     

Healthy mind in healthy body? A review of sensorimotor–cognitive interdependencies in old age

We review four broad lines of research on couplings between sensorimotor and cognitive aging, with an emphasis on methodological concerns. First, correlational cross-sectional and longitudinal data indicate increasing associations between sensorimotor and cognitive aspects of behavior with advancing age. Second, older adults show greater performance decrements than young adults when sensorimotor and cognitive tasks or task components need to be performed concurrently rather than in isolation. Third, aerobic fitness interventions produce positive transfer effects on cognition that are particularly pronounced for tasks with high demands on attention and executive control. Fourth, neuroscience findings from animal models and humans have identified aging-sensitive structural and functional circuitries that support cognitive functions and are enhanced by higher levels of sensorimotor functioning. We conclude that sensorimotor and cognitive aging are causally related and functionally interdependent and that age-associated increments in cognitive resource demands of sensorimotor functioning are malleable by experience.