To investigate differences in perfusion and water diffusivity in the hippocampus of patients with mild cognitive impairment (MCI) versus healthy, age-matched controls.

Magnetic resonance and SPECT images were obtained on eleven MCI subjects (74 ± 7 years) and 13 healthy elderly controls (75 ± 4 years). The hippocampus was traced on high resolution coronal SPGR MR images. DWI and ADC maps were obtained with EPI acquisition. The reference DWI was co-registered with the 3D MR images to obtain the transformation matrix, and the 3D hippocampal tracing was mapped to the ADC map to obtain the mean hippocampal ADC. Cerebral perfusion was measured with SPECT imaging 45 minutes after injection of Tc-ECD. Hippocampal perfusion was obtained by co-registering the MRI-guided hippocampal tracing to the SPECT images. The hippocampal perfusion was then normalized to cerebellar perfusion. A neuropsychological test battery was administered to assess cognitive performance.

The MCI group demonstrated lower hippocampal perfusion than the control group, although the difference was only significant on the right (p < 0.05). Mean ADC was higher in the MCI group than the healthy controls in the bilateral hippocampi (p < 0.05). Linear correlation analysis showed a positive correlation between ADC in the right hippocampus and age (r = 0.497, p = 0.014). After adjusting for the effect of age, performance on the 30 minute and 5 minute delayed recall of the CERAD word list was negatively correlated with the ADC in the right hippocampus (r = - 0.72, p = 0.001 and r = - 0.62, p = 0.006), i.e. higher hippocampal ADC was associated with lower memory scores.

Our results indicate that there is lower perfusion and higher ADC in the hippocampus of MCI subjects compared to controls. These findings may reflect functional and physiologic changes which precede the ultimate development of hippocampal atrophy that is seen in Alzheimer patients. Hippocampal perfusion and ADC may therefore serve as early markers to identify those individuals who would benefit from intervention to slow the progression to Alzheimer disease and to monitor the effects of treatment.