In Alzheimer's disease (AD), SPECT imagining of regional cerebral blood flow (rCBF) has emphasized deficits in the posterior association cortex. Previous studies have shown an association between these deficits and cognitive performance, both on overall cognitive tests and more specific tests such as praxis and language. Frontal deficits have been reported in more severe patients. This has led to the conclusion that the deficit in AD, at least with functional neuroimaging, starts in the posterior association cortex, and later in the disease process "spreads" to involve the frontal cortex. This study set out to measure, in a group of AD patients, the change over time of cognitive performance and the pattern of functional deficit measured by neuroimaging. Change in function was measured using 99TCm-HMPAO and SPECT and change in cognitive function using the CAMCOG. Two time points were used, 0 and 2 years. Twenty-four patients satisfying the DSM-III R criteria for probable AD were studied, nine of whom were subsequently diagnosed as having AD at post-mortem. The most striking finding was the effect that decreases in frontal lobe function had on cognitive function. A similar study by the same group, using the same techniques and many of the same patients but at only one time point, showed a correlation between cognitive function and rCBF in the parietal and posterior temporal lobes. This suggests that as AD patients deteriorate from unaffected to mild or moderately affected, the posterior association cortex exerts the greatest effect on cognitive deficit. In this longitudinal study, we found, using a MANOVA, that there were significant decreases over time for all the cortical regions studied, but that no region decreased significantly more than any other. In addition we found a correlation between change in frontal rCBF and change in cognitive function (both overall cognitive function and the CAMCOG sub tests of language and praxis). These data suggest, in contrast to the previous study, that as the disease progresses from mild or moderate to moderate or severe, the frontal cortex exerts the greatest effect on cognitive decline. These data support the concept of the deficit in functional imaging spreading from posterior to anterior as the disease progresses. However, both the initial pattern of deficit and the change over time were very heterogeneous when examined qualitatively. A posterior to anterior spread is the predominant pattern for the group as a whole, but individual patients, and possibly groups of patients, may well show alternative patterns.