Linking hippocampal structure and function to memory performance in an aging population

Abstract

Background: Hippocampal atrophy and reductions in basal cerebral blood volume (CBV), a hemodynamic correlate of brain function, occur with cognitive impairment in Alzheimer disease, but whether these are early or late changes remains unclear. Magnetic resonance imaging is used to assess structure and function in the hippocampal formation.

Objective: To estimate differences in the associations of hippocampal and entorhinal cortex volumes and CBV with memory function in the early and late stages of cognitive impairment by relating these measures to memory function in persons with and without dementia who underwent detailed brain imaging and neuropsychological assessment.

Design: Multivariate regression analyses were used to relate entorhinal cortex volume, entorhinal cortex CBV, hippocampal volume, and hippocampal CBV to measurements of memory performance. The same measures were related to language function as a reference cognitive domain.

Setting: Community-based cohort.

Participants: Two hundred thirty-one elderly Medicare recipients (aged > or =65 years) residing in northern Manhattan, New York.

Main outcome measures: Values for entorhinal cortex volume, hippocampal volume, entorhinal cortex CBV, and hippocampal CBV and their relation to memory performance.

Results: No association was noted between entorhinal cortex volume or hippocampal CBV and memory. Decreased hippocampal volume was strongly associated with worse performance in total recall, and lower entorhinal cortex CBV was associated with lower performance in delayed recall. Excluding persons with Alzheimer disease, the association of entorhinal cortex CBV with memory measures was stronger, whereas the association between hippocampal volume and total recall became nonsignificant.

Conclusions: In the early stages of Alzheimer disease or in persons without dementia with worse memory ability, functional and metabolic hippocampal hypofunction contributes to memory impairment, whereas in the later stages, functional and structural changes play a role.

Figure 1

T1-weighted images for acquisition of hippocampus volume. Borders of the hippocampus were traced manually in the coronal orientation with simultaneous monitoring for accuracy in the sagittal and axial orthogonal views.

Figure 2

CBV maps of the hippocampal formation. As described in the methods section, a sagital scout image is used to identify the long axis of the hippocampal formation (red stippled line in the ‘pre-acquisition panel), and slices are then acquired perpendicular to this axis. High-resolution T1-weighted images are subsequently acquired before and after injection of a contrast agent. Cerebral blood volume (CBV) maps are generated by subtracting the pre-contrast from the post-contrast scan and dividing the subtracting images by the degree of contrast enhancement observed in the sagital sinus (red triangle in ‘post-acquisition’ panel). Post acquisition, anatomical criteria are used to identify regions-of-interest (ROIs) of the hippocampal subregions. The anatomic locations of the four hippocampal subregions are shown in a postmortem hippocampal slice (top left panel of post-acquisition images; EC: entorhinal cortex, DG: dentate gyrus, CA1: CA1 subfield, SuB: subiculum). By identifying the external morphology of the hippocampal formation (white line in bottom left and right panels) and its internal architecture (black line in the bottom left and right panels), regions of interest can be drawn in the entorhinal cortex (green), dentate gyrus (blue), CA1 subfield (red), and the subiculum (yellow).