Successful aging has been on my mind more and more these days. Time flows forward and I am now reasonably certain that I'm not getting any younger. Thankfully, cognitive reserve (CR) gives me a reason to be hopeful: although I never made it to the Boston Symphony Orchestra or the Olympic medals platform, perhaps all those French horn lessons and 6 am swim-team practices will ultimately pay off.
Cognitive reserve has been a fertile heuristic for the past 20 years. CR explains the observed diversity of clinical expression across individuals with similar levels of underlying neuropathology. The history of the CR construct dates back to the observation of differential vulnerability to Alzheimer's disease pathology as a function of years of education (Katzman et al., 1988). Yaakov Stern stands out as the most articulate and productive thinker in the CR arena. Stern and his group at Columbia have pushed the CR concept forward and catalyzed a wide array of collateral investigations on everything from the genetics of CR factors to the influence of social activities on late-life cognitive function. Cognitive Reserve: Theory and Applications is an edited volume that provides a panoramic view of this field. The book updates and extends a 2003 special issue of the Journal of Clinical and Experimental Neuropsychology; six new chapters extend the scope of the original collection of 12 papers. The chapters take the reader on a wide-ranging tour of where the CR construct has traveled in the 20 years since Katzman's report.
Stern clearly articulates the structure of CR in the opening chapter, distinguishing between brain reserve and cognitive reserve. The former is viewed as a passive form and relates to physical aspects of the brain, such as size, neuronal count, and synaptic density. Cognitive reserve is construed as an active process, relating to information processing efficiency and capacity for compensatory function. Clearly, these two forms of reserve are interrelated. Stern describes two input streams that form the basis for CR: neural reserve, which entails utilization of more efficient or flexible neural networks, and neural compensation through which new brain networks are activated in response to disease or injury. CR applies to acute and gradually progressive disorders, as well as normal age-related change. Because of the experiential input to CR, it is dynamic and malleable and closely related to the concept of lifespan plasticity.
Although the chapters comprising Cognitive Reserve: Theory and Applications are not explicitly grouped, several threads run throughout the volume. The first three chapters provide a conceptual framework for the CR construct, reviewing the genetics of cognitive abilities and surveying the categories of acquired experience that constitute a major component of CR. In Chapter 2, Lee reviews numerous studies of genetics and cognitive function and highlights the enormous challenge of parsing gene × environment interactions. Richards et al. (Chapter 3) present a simple structural model for the development of cognitive function and their life course model, enumerating classes of variables that interact to give rise to and modify CR, ultimately shaping the clinical expression of a disease.
The next four chapters and two later chapters consider CR in the context of various disease states. In Chapters 4 and 5, Dennis et al., and Bigler, respectively, consider the role of CR in the clinical contexts of early brain injury and TBI in the mature individual. Bigler cites studies correlating brain size with IQ and posits total brain volume as a marker of CR. Boyle et al. (Chapter 6) propose electroconvulsive therapy and coronary artery bypass graft surgery as pseudo-experimental designs which provide naturalistic opportunities for further understanding the way in which premorbid CR factors influence recovery from cerebral insult. Bieliauskas and Antonucci (Chapter 7) briefly review data on the influence of premorbid functioning on disease progression, including cardiovascular disease, chronic obstructive pulmonary disease, dementia, hepatitis C, human immunodeficiency virus (HIV), and systemic lupus erthematosus/autoimmune disorders and emphasize the importance of considering baseline CR measures in evaluating outcomes from clinical trials. Reinhard et al. (Chapter 12) and Mortimer et al. (Chapter 14) utilize CR as a lens through which to better understand the cognitive course in HIV and neurodegenerative dementia.
Chapters 8 through 11 focus on the accrual of CR across the lifespan. Particularly intriguing is the connection between early-life physical activity and late-life cognitive function, found in a large longitudinal study from the Netherlands and reviewed by Dik et al. in Chapter 8. Manley et al. make the point, in Chapter 13, that common indices of CR (e.g., years of education) may not be universally applicable, for example, among minority cohorts with limited educational opportunities caused by adverse socioenvironmental factors. Chapters 15 through 17 explore the neural basis for CR through functional magnetic resonance imaging (fMRI) and evoked response potential (ERP) paradigms. Stern (Chapter 15) presents functional magnetic resonance imaging and positron emission tomography data that identify networks and functionally connected regions that may form the neural basis for CR. He describes voxel-based and covariate analyses to illuminate differences in task processing as a function of CR. In Chapter 16, Grady examines the compensatory impact of CR in both normal aging and Alzheimer's disease. An emphasis is placed on the importance of viewing the entire brain to understand the compensatory response engendered by CR; recruitment of networks and regional deactivations are viewed as aspects of this response. Friedman (Chapter 17) acknowledges that we are at the earliest phase of understanding the meaning of ERP data in studying age-related processing differences in tasks of episodic memory and executive function. Do these differences reflect bona fide evidence of CR, or are they simply reflecting differences in the way older brains function? Friedman advocates the integration of ERP and fMRI in order to glean the respective advantages of these two techniques in optimizing temporal and spatial resolution.
Although the term reserve is nowhere to be found in Kozorovitskiy and Gould's final chapter (18) on brain plasticity and neurogenesis, it is clear that these concepts are central to the brain's response to normal aging and injury. In turn, gaining an understanding of the complex gene × environment interactions previewed in Lee's earlier chapter will be fundamental to illuminating the link between plasticity and CR.
CR is an enormous, sprawling construct. It comprises genetic and acquired/experiential inputs as well as the complex interactions between these sets of factors. Perhaps the major challenge posed by the magnitude of CR is delimiting where it begins and where it ends. Between innate factors, life experiences, and their associated interactions, what isn't included in CR? The need to further sharpen and focus the CR construct is reflected in the occasional inconsistency in terminology used by the authors from chapter to chapter. For example, brain reserve and cognitive reserve are used interchangeably in some instances. This inconsistency in terminology both reflects and seems to drive inconsistencies in independent variable measures being utilized in various studies. Should we be measuring intracranial volume or lexical ability? Or both? Composite variables (factors) have been proposed and seem promising.
Dependent variable issues also need to be addressed. To understand how CR operates as a neuroprotective factor, should we be measuring differences in absolute terms? Or, should measurements be based on proportional change from an estimated baseline? Or, perhaps we should simply set cross-over from normalcy to disease as the dependent variable event. Does CR delay the onset of clinical dementia in an extremely intelligent elder simply because the individual has further to decline before crossing an admittedly arbitrary threshold? In viewing CR in the context of brain injury or disease, accounting for size and location of lesion would seem to be critical, particularly if we take the neural networks model seriously. Given the strength of preliminary investigations using functional imaging technology, Stern and colleagues will continue to lead the discussion on advancing methodological approaches.
Like the black hole in astronomy and the subatomic particle in physics, CR's importance and power of explanation become manifest in its influence on adjacent phenomena. Since its introduction into our thinking about the brain, CR must be part of the dialogue in any serious discussion of normal aging and response to disease/injury. CR has become fundamental to our understanding of the neuropsychological cosmos. Cognitive Reserve: Theory and Applications provides clinicians and researchers with a detailed recounting of CR's journey to date, and a glimpse of the distant horizon. Despite some of its flaws and because of the many important questions it raises but cannot yet answer, I highly recommend Cognitive Reserve: Theory and Applications to clinicians and researchers alike.
