Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD

Objective: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). Methods: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. Results: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE ε4 allele than in the 16 noncarriers. Conclusions: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.