Structure of the Brain

It will be useful at this point to provide a brief overview of the anatomy of the human brain (see Figure 2.1). Neuroanatomy is fundamental to the discipline of neuroscience, and we will refer to a number of brain regions that exhibit age- related changes in both structure and function. The cerebral cortex is the area to which neurosci­ence has dedicated most of its effort. In this area, there are two major hemispheres, right and left, which are linked via a thick bundle of axons called the corpus callosum.

Each region of the brain has distinguishing features. For example, in most people, language processing is associated primarily with the left hemisphere, whereas recognizing nonspeech sounds, emotions, and faces is associated with the right hemisphere. As we shall see in the fol­lowing sections, the frontal cortex is a focal area for research. This area is intimately involved in higher-order executive functions such as the abil­ity to make and carry out plans, switch between tasks, and maintain attention and focus. In addi­tion, there is the cerebellar cortex which contains the cerebellum. Details regarding the functional aspects of the various regions of the brain will be discussed more fully with respect to age-related change.

Age-Related Changes in the Structure of the Brain. The

majority of studies examining structural changes

in the brain as we grow older have applied a corre­lational approach by employing postmortem anal­yses of young and older adult brains or by using cross-sectional and longitudinal designs to exam­ine age differences in the brain using structural MRI techniques. In these studies, different regions of the brain are examined in terms of thinning and shrinkage in volume and density. Other struc­tural deficiencies can also be detected such as the declining health of the white matter of the brain, or white matter hyperintensities (WMH). WMH is determined by the observation of high sig­nal intensity or a bright spotty appearance which indicates brain pathologies such as myelin loss or neural atrophy (Nordahl, Ranganath, Yonelinas, DeCarli, Fletcher, & Jagust, 2006).

Overall, postmortem and neuroimaging studies demonstrate that considerable shrinkage occurs in the aging brain. However, this shrinkage is selective (Raz & Rodrigue, 2006). For example, the prefrontal cortex, the hippocampus (which is associated with memory), and the cerebellum show profound shrinkage (Raz & Rodrigue, 2006). The sensory cortices, such as the visual cortex, show relatively little shrinkage.

The white matter area also shows deterioration with increasing age. A neuroimaging method called diffusion tensor imaging (DTI) assesses the rate and direction that water diffuses through the white matter. This results in an index of density or struc­tural health of the white matter (Park & Reuter — Lorenz, 2008). By using DTI, studies examining WMH have demonstrated that such disruptions of white matter integrity may represent a mechanism for prefrontal cortex dysfunction in older adults (Nordahl et al., 2006). As we will see later, this has important implications for cognitive functioning in older adulthood. Of particular importance is the fact that WMH are linked to cerebrovascular dis­ease (e. g., hypertension), which is preventable and can be treated through medication and changes in lifestyle. The critical issue is that it is possible that some of the age-related cognitive decline we observe can be treated or even prevented (Nordahl et al., 2006).

An important question to ask in order to under­stand the impact of these deteriorating structural changes in the aging brain is how they relate to cog­nitive functioning. With increasing age, many facets of information processing become less efficient,

including speed of processing, executive function, and declarative long-term memory. Memory and executive function have received a preponderance of attention in the cognitive neuroscience and aging literature. Executive functioning includes processes such as inhibitory control or the ability to control the contents of the conscious mind using working memory. Executive function failures in older adults include erroneous selection of irrelevant informa­tion to process in working memory, the inability to divert attention away from irrelevant information to the task in question, and attentional dysregula — tion such as inefficiency in switching tasks among others (Park & Reuter-Lorenz, 2008). For example, when older adults are reading an article that is filled with information that is true and false, even if they are told which information is false, they still have a difficult time factoring out the false information in their understanding of the article.

Some evidence suggests that volume shrinkage in the brain is linked to poor cognitive perfor­mance on such tasks. For example, WMH in non­demented, healthy older adults have been linked to lower cognitive test scores and decreased executive functioning (de Groot, de Leeuw, Oudkert, van Gijn, Hofman, Jolles, & Breteler, 2002; Madden, Whiting, Huettel, White, MacFall, & Provenzale,

2004) . Poor performance on executive functioning tasks has also been linked with decreased volume of the prefrontal cortex (Raz & Rodrigue, 2006). Studies also have shown that observed reductions in cortical volume in the hippocampal regions are related to memory decline (Rosen, Prull, Gabrieli, Stoub, O’Hara et al., 2003). It should be noted, however, that studies of the role of frontal volume as a predictor of cognitive function have yielded some inconsistent findings. Whereas some studies have found prefrontal volume to be linked to work­ing memory performance (holding and manipulat­ing information in consciousness); Salat, Kaye, & Janowsky, 2002), others have not (Gunning-Dixon & Raz, 2003). Nevertheless, overall, the majority of evidence suggests that age-related change in fron­tal regions of the brain correlates with executive dysfunction and memory decline (Buckner, 2004).

Similar to the point made earlier regarding WMH, Buckner (2004) points out that age-related decline in vascular functioning may affect white matter struc­tures that underlie the areas important to executive functioning. Finally, decline in other areas of cogni­tive performance has been differentially linked to specific brain regions. Acquiring new skills has been linked to volumes of the striatum, prefrontal cortex, and cerebellum; spatial memory has been linked to hippocampal volume (Raz & Rodrigue, 2006).

The neuropsychological approach also has shed light on the link between structural changes in the aging brain and cognitive functioning. A prolifera­tion of research has examined specific areas in the temporal lobe (medial-temporal) and its influence on memory by examining patients with Alzheimer’s disease. For example, brain atrophy, cellular pathol­ogy, and cell loss are observed in this region of the brain in Alzheimer’s patients, who also show profound memory impairment (Buckner, 2004). As Buckner points out, this has raised challenges to aging research by asking the question about whether Alzheimer’s disease is reflective of an accel­eration of normal aging processes as opposed to a disease process. Indeed, research on nondemented older adults has found similar correlations between medial-temporal lobe atrophy and poor memory performance (Rodrigue & Raz, 2004), although again this conclusion is not straightforward, as other studies have not found such an association (Van Petten, 2004).

In a recent review, Raz and Rodrigue (2006) pointed out that much of the conflicting findings in this area could be a result of the sample com­position, whether cross-sectional differences or longitudinal changes are being examined, whether different subregions are under investigation, and whether different cognitive tests are used. One way to handle some of these concerns is to pro­vide converging evidence from both cross-sec­tional and longitudinal studies of brain structure changes. For example, Raz and Rodrigue (2006) point to converging evidence between these two approaches that suggests age-related increases in white matter lesions. In addition, the prefrontal

cortex, hippocampus, and cerebellum appear to be aging-sensitive. With respect to linkages between brain structure and cognitive performance, longi­tudinal studies indicate a stronger relationship. By examining individual differences in change, longi­tudinal studies converge with cross-sectional stud­ies showing that increases in WMH are associated with reduced performance on executive function­ing tasks (Cook, Leuchter, Morgan, Dunkin, Witte, David et al., 2004).