Alterations to the working memory network in normal aging and alzheimer's disease

The working memory system, particularly the central executive component, is impaired early in the course of Alzheimer's disease (AD). Decline in working memory is, however, also observable in the course of normal ageing. The present study sought to investigate the differences between normal and pathological ageing using an n-back working memory fMRI paradigm. The participants were twenty-five patients with probable AD, six individuals with mild cognitive impairment (MCI) of amnestic type, eight elderly controls and nine young controls. The AD group was divided into two smaller sub-groups, one age matched to the elderly controls, and one including patients significantly older than the elderly controls. The aim of the study was to determine whether brain activations within the working memory network of patients and controls showed any distinctive differential feature which might be useful in the detection of abnormal decline. The individuals with MCI were followed up for four years, divided into converters and non-converters, and analysed in this form. The results showed that greater differences in the activation patterns occurred with pathological rather than normal ageing. The young AD group, old AD group and MCI converters all failed to significantly activate the left inferior parietal lobule (an area associated with phonological storage) which was activated by the young controls, the elderly controls and the MCI non-converters. The findings indicate that brain activation paradigms can be useful to detect brain activation differences indicative of pathological working memory decline. The results have to be taken with caution, however, given the small sample size of the MCI sub-groups, which restricted the use of between-group statistical comparisons