Post mortem studies suggest that lesions in the hippocampal formation precede neocortical lesions and dementia symptoms of AD. Recent MRI results are in agreement and expand these findings. The cross-sectional MRI data show that hippocampal formation atrophy (n=405) and volume loss (n=79) (HA) discriminate between normal elderly and elderly with mild cognitive impairments (at increased risk for AD). After controlling for age, HA is a specific anatomic predictor of memory performance. Including the lateral temporal lobe volume serves to improve the detection of patients with dementia. The longitudinal data show that baseline HA is an accurate predictor of dementia within 4 years. We now observe that many of these relationships are observable on the PET with FDG.Basic studies consistently point to relationships between HPA axis functioning and hippocampal integrity. In AD, glucose tolerance tests caused hypercortisolemia which was associated with increased HA. With the IV infusion of cortisol we observe, using PET, marked hippocampal glucose metabolism reductions in elderly controls (n=7) but not in AD (n=8). These results contribute both to the increased understanding of normal hippocampal functioning and to the detection of early AD.