Evidence that volume of anterior medial temporal lobe is reduced in seniors destined for mild cognitive impairment

Abstract

The present study sought to determine if volumes of specific brain structures could discriminate cognitively normal seniors destined to develop mild cognitive impairment (MCI) within a few years from those who will remain normal. Brain scans were collected from seventy-one cognitively normal seniors. Seventeen individuals later developed MCI (the presymptomatic MCI; pMCI group), while fifty-four remained normal. Whole brain volume (WBV) and volumes of the entorhinal cortex (ERC), hippocampus, and three subregions of the hippocampus (head; HH, body; HB and tail; HT) were compared. Results indicated that the pMCI group had smaller volumes than the normal group in the ERC, HH and HB, but not the HT or WBV. When HH/HB volumes and baseline memory test scores were included in a single logistic regression model, classification accuracy was very high (area under the curve=0.93). These results show that smaller normalized volumes of anterior medial temporal lobe structures contribute to the development of MCI, a finding which may have implications for identifying seniors at risk for cognitive decline.

Fig. 1

Example of whole brain volume measurement on three axial slices. Thresholding was set to include parenchema and exclude ventricular compartments and CSF in sulci, as indicated by the boundary between the red contour lines.

Fig. 2

Anatomic boundaries used for manual tracing of the hippocampus and its subregions. (A) Approximate locations of the hippocampal head (HH), hippocampal body (HB), and hippocampal tail (HT) in a sagittal plane. The boundary between the amygdala (Am) and HH was demarcated in the sagittal plane where the alveus (denoted by the arrow) can be seen to clearly divide the two structures. Panels (B–D) show examples of one anterior slice of each hippocampal subregion in the coronal-oblique plane in which tracing was performed. (B) The anterior boundary of the HH was demarcated through automatic transfer of the alveus position from the sagittal plane (see panel (A)) to the coronal-oblique plane. The uncus (denoted by arrow) demarcates the HH from the HB. (C) The anterior boundary of the HB was demarcated as the first slice in which the uncus is no longer visible. The white matter of the parahippocampal gyrus (denoted by arrow) represents the inferior hippocampal boundary. (D) The anterior boundary of the HT was demarcated as the first slice in which the crus of the fornix (denoted by arrow) is in view.

Fig. 3

Anatomic boundaries used for manual tracing of the entorhinal cortex (ERC). The ERC was traced on three consecutive coronal images centered at the level of the mammillary bodies (Mb). The rhinal sulcus (Rs) demarcated the inferior boundary. The lateral boundary was demarcated by parahippocampal white matter (Pwm) on the inferior-medial surface of the hippocampal head (HH). Tracing began at the angle formed by the junction of the rhinal sulcus and the surface of the brain. The outline then transected the angle formed by the rhinal sulcus and the inferior-medial surface of the brain, proceeding across the gray matter to the white matter. Tracing then proceeded along the gray-white boundary to the inferior surface of the hippocampus. Finally, the outline followed the lateral surface of the brain back to the starting point.

Fig. 4

Receiver operator characteristic (ROC) curves. The area under the curve (AUC) was 0.90 for the volume of HH and HB (panel (A)), and 0.81 for the word list delayed, and WMS total (panel (B)). Combining the HH and HB volumes and memory scores into one model improved the AUC to 0.93 (panel (C)).