Age and disease effects on working memory

McGeown, William and Venneri, Annalena; Jeong, Hyun, ed. (2008) Age and disease effects on working memory. In: Alzheimer's Disease in the Middle-Aged. Nova Science Publishers, Inc., New York, pp. 67-96. ISBN 978-1-60456-480-8

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There is a large body of evidence which has established the neural network supporting working memory (WM). Several functional imaging studies have identified functional changes within this network in the course of physiological brain ageing. Behavioural studies have also shown that in the course of pathological cognitive decline, for example that due to Alzheimer’s disease (AD), WM deficits are detectable very early and appear different from those of normal ageing. In normal ageing, WM decline may be due to slower processing, a reduced capacity for inhibition or a less highly directed attentional focus. Healthy elderly, therefore, appear to mostly use the same cognitive processes as the young, just not as effectively. In AD on the other hand, the drop in WM capacity and performance appears to be due to different causes, for example, disease related functional and anatomical impairments. WM decline also tends to be more severe in AD. These behavioural hypotheses can be tested using functional magnetic resonance imaging (fMRI) working memory paradigms. Through fMRI, it is possible to detect abnormalities in the activation patterns of patients with AD when compared to normal ageing individuals. People that are in the preclinical stages of AD should be expected to have malformed patterns of brain activity underlying the behavioural deficits. These differences may vary from increases in activation (compensatory effects) to decreases or absences of activation in task relevant areas. Both of these effects are likely to be due to early disease related pathology and/or genetic influences. Differences should be robust in middle-aged individuals with preclinical AD, as confounds such as the physiological effects of age would not be as prominent (compared to the very elderly) and if healthy, a high level of cognitive functioning would be expected. This approach, now confined to research, might be translated into clinical application and provide a way to increase confidence in clinical diagnosis very early in the disease process. In this chapter behavioural and functional neuroimaging studies on the effects of normal and pathological ageing on working memory will be reviewed. Original results of fMRI studies demonstrating the differences in brain activation patterns between young and elderly people and younger and older patients with AD will also be included. A prospective validation study of diagnostic techniques of this kind in individuals who experience mild cognitive impairment who have a greater risk than the normal ageing population of developing AD will also be presented.