Longitudinal Cognitive, Electroencephalographic and Morphological Brain Changes in Ageing and Alzheimer's Disease

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Abstract
Background: The natural course of cognitive performance, electrophysiological alterations and brain atrophy in ageing and Alzheimer's disease (AD) has been investigated in numerous studies, but only few attempts have been made to examine the relationship between clinical, electroencephalographic (EEG) and morphological changes with quantitative methods prospectively over longer periods of time.Method: Fifty-five patients with clinically diagnosed AD and 66 healthy elderly controls were examined biannually using a cognitive test (CAMCOG), EEG band power and volumetric estimates of brain atrophy.Results: On average cognitive performance deteriorated by 28 points on the CAMCOG in the AD group, the alpha/theta ratio decreased by 0.2, and the proportion of intracranial cerebrospinal fluid volume increased by 3.5% during a 2-year period. Similar changes were observed after a second 2-year interval. A multiple regression model demonstrated a significant influence of age on cognition and atrophy and a significant influence of the estimated duration of symptoms on cognition, alpha/theta ratio and brain atrophy at the initial examination. Cognitive performance at the first examination exerted significant effects on the performance and also on brain atrophy at re-examination after 2 or 4 years, whereas the EEG and neuroimaging findings at the previous examination were exclusively related to the corresponding findings at the follow-up examinations. In the control group no significant cognitive, EEG and morphological changes were observed after 2 and 4 years.Conclusion: After 2 consecutive follow-up periods, we were able to verify significant deteriorations of cognition accompanied by neurophysiological and neuroradiological changes in AD, but not in normal ageing. In clinically diagnosed AD, cognitive performance at the follow-up examination could not be predicted by the previous alpha/theta ratio or by the previous degree of global brain atrophy, whereas the cognitive test score determined not only performance, but also structural findings at follow-up. Performance on cognitive tests appears to be a more sensitive indicator of the degenerative process than EEG band-power and morphological changes in manifest AD. Neuroimaging, neurophysiology and genetic risk markers may be more important for the early differential diagnosis than for the prediction of the course of illness.