A total of 30 patients with clinically diagnosed Alzheimer's disease and 55 healthy, age-approximated controls were followed up over a 2-year period to compare the course of functional and cognitive impairment, quantitative morphological and functional brain changes. No remarkable changes were observed within the control group in any of these modalities. There were significant differences between patients and controls at the first examination: Mini-Mental State Examination (MMSE), 16.1 +/- 7.3 compared with 28.7 +/- 1.4; left lateral ventricle 2.7 +/- 1.1% versus 1.6 +/- 0.7% of the total intracranial volume; right lateral ventricle 2.7 +/- 1.4% versus 1.4 +/- 0.4%; absolute delta-power 1.1 +/- 0.3 versus 0.9 +/- 0.2 microV2; and absolute theta-power 1.1 +/- 0.3 versus 0.8 +/- 0.2 microV2 (means +/- standard deviation). In the patient group, scores on the Blessed dementia rating scale deteriorated from 10.6 +/- 6.1 to 17.9 +/- 9.6; the MMSE decreased by 8.0 +/- 3.7; the left lateral ventricle volume increased by 0.9 +/- 0.7%, the right by 0.9 +/- 0.7% of the total intracranial volume; absolute delta-power increased by 0.2 +/- 0.4 microV2 and theta-power by 0.1 +/- 0.3 microV2. We could not confirm a relationship between age, age at onset or apolipoprotein E4 gene dose and the rate of clinical change. High initial Blessed dementia scores were correlated with more severe ventricular enlargement, and delta-theta increase during the follow-up period. High initial theta-power predicted more severe functional and cognitive deterioration. To our knowledge, this is the first longitudinal study reporting quantitative clinical, morphological and EEG-changes measured in two points in time in patients and non-demented controls.