Characterization of age-related microstructural changes in locus coeruleus and substantia nigra pars compacta

Abstract

Locus coeruleus (LC) and substantia nigra pars compacta (SNpc) degrade with normal aging, but not much is known regarding how these changes manifest in MRI images, or whether these markers predict aspects of cognition. Here, we use high-resolution diffusion-weighted MRI to investigate microstructural and compositional changes in LC and SNpc in young and aged cohorts, as well as their relationship with cognition. In LC, the older cohort exhibited a significant reduction in mean and radial diffusivity, but a significant increase in fractional anisotropy compared to the young cohort. We observed a significant correlation between the decrease in LC mean and radial diffusivities and measured examining delayed recall. This observation suggests that LC is involved in retaining cognitive abilities. In addition, we observed that iron deposition in SNpc occurs early in life and continues during normal aging. Since neuronal loss occurs in both LC and SNpc in Parkinson's disease, but occurs only in the LC in Alzheimer's disease, our results may lead to early stage imaging biomarkers for these diseases.

Increased iron-deposition in lateral-ventral substantia nigra pars compacta: A promising neuroimaging marker for Parkinson's disease

“…The present result accords well with our prior work despite the age difference between the two control cohorts, and this agreement may suggest that iron deposition in the SNpc derived from NM-MRI is not dependent on age in normal subjects and is primarily due to PD. Additionally, SNpc R 2 * values in the control group are in line with those published in an earlier study examining age-related iron deposition in SNpc ( Langley et al, 2020 ).…”

Locus coeruleus MRI contrast is associated with cortical thickness in older adults

“…A growing body of literature has suggested that the LC-NE system plays a role in cognition in later life, with recent studies linking in vivo estimates of LC neuronal integrity to cognitive outcomes in older adults (Clewett et al, 2016;Dahl et al, 2019;Hämmerer et al, 2018;Langley et al, 2020). In this study, we aimed to build upon this literature to determine whether LC neuronal integrity predicted cortical thickness, one aspect of brain structure and a documented brain indicator of cognitive ability in older adulthood (Fjell et al, 2006;Lee et al, 2016).…”

What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease

“…Measures of mean, radial, and axial diffusivity would help clarify precise changes to LC axons over the course of disease. In healthy participants, aging appears to increase fractional anisotropy and lowers both mean and radial diffusivity of the LC ( Langley et al, 2020 ). The authors propose decreased LC axon diameter underlie these results, but follow up studies should directly test this hypothesis.…”