Hippocampal Surface Analysis in Subjective Memory Impairment, Mild Cognitive Impairment and Alzheimer's Dementia

Background/aims: Alzheimer's disease (AD) is preceded by prodromal states. To determine the neuroanatomical basis for the relationship among such states, we assessed surface conformations of the hippocampus in AD, mild cognitive impairment (MCI) and subjective memory impairment (SMI).

Methods: Hippocampal surfaces were reconstructed three-dimensionally via large-deformation high-dimensional MRI brain mapping in 14 SMI, 15 MCI, 12 AD and 13 controls. The surfaces were divided a priori into lateral, superior and inferior-medial zones, which approximated the CA1, combined CA2, CA3, CA4 subfields and the subiculum, respectively.

Results: Group differences reached statistical significance in the lateral zone (F = 3.2, d.f. = 3, p = 0.033) and inferior-medial zone (F = 2.8, d.f. = 3, p = 0.049) subfields. The groups differed in total hippocampal volume only at the trend level (F = 2.5, d.f. = 3, p = 0.071). Surface deformation maps revealed similar patterns in SMI, MCI and AD subjects, but quantitative differences were significant only when comparing MCI and AD with control subjects.

Conclusions: Hippocampal surface deformation in the CA1 subfield was most pronounced in AD, less so in MCI and minor in SMI subjects. These results suggest that hippocampus degeneration develops gradually in AD, and may be observable long before dementia is apparent.