Old age puts more wrinkles in our minds than on our faces.
— Michel de MontaigneAging has long been known to be associated with declines in cognitive abilities. Historically, investigations of the effects of age on cognition have been approached from divergent perspectives, with some researchers focused on cognitive concepts such as memory and processing speed and others focused on neuroanatomical changes. Although age-related cognitive decline has always been postulated to reflect concomitant declines in brain structure and function, integrative research combining these two perspectives is in its relative infancy. Over the past 20 years, a wealth of neuroimaging methods have been developed that allow the in vivo examination of brain function while individuals are performing cognitive tasks, for example, functional magnetic resonance imaging (fMRI). These methods have sparked a burgeoning field of research, the cognitive neuroscience of aging, which links age-related cognitive changes to underlying neuroanatomical mechanisms.
In 2002, the first Symposium on Neuroscience, Aging & Cognition was held in San Francisco at the Annual Meeting of the Cognitive Neuroscience Society. Organized by the editors of this book, world-renowned experts and founding researchers in the field met to review this rapidly growing field. This book grew out of that 2002 conference and serves as a comprehensive review of research in this area thus far, including detailed methodological techniques and potential confounds, reviews of age effects on cognition and neuroimaging variables, and many ideas for future work. The text is divided into four sections: imaging methods (five chapters), age effects on cognition (four chapters), clinical applications (three chapters), and theories relating cerebral and cognitive aging (two chapters). Importantly, given the visual nature of neuroimaging results, the text contains a multitude of useful tables and figures, including several color inlays, which help translate research findings into easily comprehensible take-home points.
Chapter 1 written by the editors serves to introduce cognitive neuroscience of aging as a new discipline and presents an overarching model of the interactive relationship between cognition and brain function during aging. The rest of the chapter provides an excellent summary of key points from each subsequent chapter and will be a valuable overview of the book for those with less technical background.
In the first section of the book, imaging methodologies and their applications are reviewed. Chapter 2, by Raz, updates a previous review of the effects of age on structural brain imaging (Raz, 2000). The results of cross-sectional and longitudinal studies of aging are discussed, highlighting the vulnerability of white matter relative to gray matter. Next, an excellent set of figures and tables summarizes the differential effects of age on regional brain volumes, with prefrontal cortex appearing the most vulnerable to age. Novel techniques such as diffusion tensor imaging that provide information about the integrity of white matter are also discussed. Last, modifying risk factors such as vascular disease, exercise, and hormone replacement therapy are discussed. Raz does a wonderful job of discussing methodological pitfalls secondary to differences in imaging techniques and the utilization of cross-sectional versus longitudinal studies.
Chapter 3, by Backman and Farde, explores the role of dopamine (DA) in age-related changes in cognition. The chapter focuses primarily on the use of DA imaging techniques using positron emission tomography and single photon emission computed tomography, which have revealed consistent age-related losses in both pre- and postsynaptic DA markers within the basal ganglia. These DA abnormalities have been associated with decreases in cognition and are discussed within the context of frontal–striatal circuitry that may contribute to the relatively greater decline in prefrontal cortex function with age. Several exciting future directions are discussed including linking specific DA receptors to more circumscribed cognitive abilities, combining DA imaging with other functional imaging methods (i.e., fMRI), and examining the influence of DA on neuromodulation using a combination of neural network models and neuroimaging methods.
Chapter 4, by Fabiani and Gratton, focuses on optical brain imaging and electrophysiological methods. These noninvasive techniques are particularly beneficial for examining the dynamic relationship between brain activity and mental processes, given their excellent temporal resolution. Thirty years’ worth of event-related potentials (ERPs) research on aging is summarized, suggesting older adults show altered deployment and gating of attention. Unfortunately, ERPs have a limited spatial resolution, which limits the extent to which these results can be ascribed to a specific brain region. This chapter goes on to describe a novel methodology, optical imaging, which provides an indirect measurement of neural activity via examining the scatter of light due to hemoglobin within tissue. This work is preliminary but exciting due to its excellent spatial and temporal resolution. As noted in the text, optical imaging may be influenced by age differences in neurovascular function (discussed further below). Thus, future work will be required to determine the relative benefits of this new technology.
One of the primary methodologies used in the field of cognitive neuroscience of aging is fMRI, which is used to compare differences in brain activity between younger and older adults during cognitive task performance. The blood oxygen level–dependent (BOLD) signal used in fMRI is an indirect measure of neural activity and is thought to reflect local changes in cerebral blood flow. Chapter 5, by Gazzaley and d’Esposito, focuses on confounding factors that may affect interpretation of the BOLD signal in fMRI studies of cognitive aging, particularly neurovascular factors. This chapter is extremely important for consumers of cognitive aging research as it has profound implications for the interpretation of fMRI studies that directly compare younger and older adults. The authors recommend strategies for avoiding age-related confounds due to blood flow, including parametric designs, correlation with behavioral measures, and novel statistical analysis techniques.
After more general discussions about neuroimaging methods used in the investigation of age-related changes in cognition, Chapter 6, by Rugg and Morcom, reviews the fMRI and ERP literature on age-related changes in episodic memory. After reviewing major findings, the authors focus on experimental design and subject selection issues that can contribute to spurious results (i.e., differential strategy use within participants, variable performance across age-groups). These first chapters provide an excellent overview of the various neuroimaging methods used in the investigation of age-related changes in brain activity and cognition. Importantly, all the chapters address potential confounds with each technique and suggest appropriate methods for future studies.
The second section of the book reviews the effect of age on basic cognitive processes. Chapter 7, by Madden, Whiting & Huettel, discusses age-related changes in brain activity during visual perception and attention. Findings have suggested an age-related decrease in the efficiency of brain activity during perception and attention, with the recruitment of regions not typically observed in younger adults. The extent to which this additional brain activity compensates for other weaknesses is a major debate within the cognitive neuroscience of aging literature and is discussed throughout the text. The relationship of age differences in these basic abilities to higher level cognitive deficits is important to determine. Additionally, the interpretation of greater brain activity and potential age-related differences in baseline activity are raised as important methodological issues that may affect analysis.
Chapter 8, by Reuter-Lorenz and Sylvester, focuses on the neural underpinnings of age-related changes in working memory. Although often treated as one entity, the various subcomponents of working memory (e.g., maintenance, processing, interference) are discussed with a detailed table listing out the results of relevant fMRI studies. A hypothesis regarding selective compensation is presented, which suggests that additional activity in the prefrontal cortex during easy tasks diminishes the resources available for more complex tasks.
Long-term memory is covered in Chapter 9 by Park and Gutchess. The chapter reviews the literature on encoding and retrieval processes while focusing primarily on activation within frontal cortex and the hippocampus. Findings of decreased hippocampal activity and increased prefrontal cortex activity are discussed within the compensation hypothesis. Last, the importance of examining interindividual differences in performance and associated brain activity within an older adult sample is highlighted.
Chapter 10, by West, provides a review of neural activity during prospective memory tasks that require participants to remember to perform future events (i.e., remembering to remember). Several cognitive models are evaluated and linked to preliminary neuroimaging studies that suggest a distributed network of regions involved in prospective memory, including frontal, parietal, and medial temporal cortex. Given this common complaint in older adults, this appears to be a ripe area for future research. Overall, this section does an excellent job of summarizing the relevant neuroimaging literature examining cognitive domains affected by age.
Section 3 focuses on clinical and applied issues. Chapter 11, by Buckner, considers three general principles for aging research. First, he postulates that multiple causal mechanisms contribute to cognitive decline in aging. For example, frontal–striatal systems may be particularly vulnerable to age, while medial temporal regions are vulnerable to Alzheimer’s disease pathology. Second, individuals vary in the extent to which they are affected by differing causal mechanisms and in their neural and behavioral response to such mechanisms. Third, he suggests that causal mechanisms of aging should be studied in an integrative fashion from a variety of perspectives (i.e., bench to bedside). This chapter provides an important perspective on the differentiation of “healthy” aging from disease, which is a critical challenge for researchers in this field.
Functional connectivity, an expansion of standard fMRI approaches, is discussed in Chapter 12 by Grady. Functional connectivity analyses examine brain activity across a network of regions rather than taking the standard region-of-interest approach. Given the highly interconnected nature of the brain, this work has the potential to provide significant insight into how age affects specific brain networks above and beyond the information provided by standard fMRI approaches.
Chapter 13, by Nyberg, reviews the concept of plasticity and cognitive training. The benefits and limits of cognitive training in older adults are discussed, with transfer of training remaining a significant hurdle. Additionally, neurobiological factors that may limit training effects and plasticity with age are reviewed. This chapter is particularly relevant, given the wealth of cognitive training software, and materials available in the marketplace focused on enhancing cognitive abilities in older adults.
Section 4 presents two models of cognitive neuroscience of aging. First, in Chapter 14, Daselaar and Cabeza discuss age-related changes in hemispheric organization. One of the most consistent findings within the cognitive neuroscience of aging literature is a reduction in lateralization with age. After reviewing hemispheric specialization and interaction, two models about age-related changes in lateralization are presented. The right hemi-aging hypothesis suggests that age may affect right-hemisphere functions to a greater extent than the left hemisphere, which is supported by research demonstrating that older adults have greater problems with spatial relative to verbal stimuli. However, as acknowledged by the authors, neurobiological explanations of this hypothesis remain unclear. Second, the HAROLD (hemispheric asymmetry reduction in older adults) model is presented. As noted previously, the additional activation seen in older adults is often interpreted as compensatory, and the authors review the evidence for and against this proposal.
The final chapter by Li explores computational approaches to the investigation of neuromodulation and cognitive aging. Following up on Chapter 3, the potential influence of deficient dopaminergic modulation with the prefrontal cortex and the resultant downstream effects (fuzzy cortical representations and behavioral deficits) are presented. The benefits of using computational approaches are many, and this method should be considered an essential tool toward understanding cognitive aging.
The goal of this book as described by the editors was to serve as a comprehensive introduction of the reader to a new discipline, and they have wildly succeeded in this endeavor. Both newcomers to the field and seasoned researchers will enjoy having this book on their shelf for frequent reference. Importantly, the significant number of limitations and confounds that currently exist within the literature are discussed openly, and suggested remedies for future studies are provided. The accelerated aging of our society begs for additional research into the etiology and potential treatments for age-related cognitive impairment. If the next 20 years can provide as much progress as is reviewed in Cognitive Neuroscience of Aging: Linking Cognitive and Cerebral Aging, we will have made fantastic strides toward this goal.