Medial temporal lobe volumes in late-life depression: effects of age and vascular risk factors

Abstract

Substantial work associates late-life depression with hippocampal pathology. However, there is less information about differences in hippocampal subfields and other connected temporal lobe regions and how these regions may be influenced by vascular factors. Individuals aged 60 years or older with and without a DSM-IV diagnosis of Major Depressive Disorder completed clinical assessments and 3 T cranial MRI using a protocol allowing for automated measurement of medial temporal lobe subfield volumes. A subset also completed pseudo-continuous arterial spin labeling, allowing for the measurement of hippocampal cerebral blood flow. In 59 depressed and 21 never-depressed elders (mean age = 66.4 years, SD = 5.8y, range 60-86y), the depressed group did not exhibit statistically significant volumetric differences for the total hippocampus or hippocampal subfields but did exhibit significantly smaller volumes of the perirhinal cortex, specifically in the BA36 region. Additionally, age had a greater effect in the depressed group on volumes of the cornu ammonis, entorhinal cortex, and BA36 region. Finally, both clinical and radiological markers of vascular risk were associated with smaller BA36 volumes, while reduced hippocampal blood flow was associated with smaller hippocampal and cornu ammonis volumes. In conclusion, while we did not observe group differences in hippocampal regions, we observed group differences and an effect of vascular pathology on the BA36 region, part of the perirhinal cortex. This is a critical region exhibiting atrophy in prodromal Alzheimer's disease. Moreover, the observed greater effect of age in the depressed groups is concordant with past longitudinal studies reporting greater hippocampal atrophy in late-life depression.

Keywords: Depressive disorder; Geriatric; Hippocampus; MRI; Perirhinal cortex; Structural.

Figure 1.. Segmentation of medial temporal subfields

Segmentation of hippocampal and medial temporal subfields conducted using ASHS (Automated Segmentation of Hippocampal Subfields; Yushkevich, et al. 2015). BA35 – orange; BA36 – turquoise; CA1 – red; CA2 – green; CA3 – yellow; dentate gyrus – dark blue; entorhinal cortex – purple; subiculum – pink. Collateral sulcus indicated in light blue, but not included in analyses.

Figure 2.. Effects of age by group on medial temporal volumes

Figures display the relationship between age (x-axis) and regional volume in milliliters (y-axis) for each diagnostic group. Depressed subjects are displayed using solid circles / solid line, while nondepressed subjects are displayed by open circles / dashed line. Left (L) and right (R) refer to each hemisphere.