Associations between locus coeruleus integrity and diagnosis, age, and cognitive performance in older adults with and without late-life depression: An exploratory study

Abstract

Late-life depression (LLD) is a risk factor for age-dependent cognitive deterioration. Norepinephrine-related degeneration in the locus coeruleus (LC) may explain this link. To examine the LC norepinephrine system in vivo, we acquired neuromelanin-sensitive MRI (NM-MRI) in a sample of 48 participants, including 25 with LLD (18 women, age 68.08 ± 5.41) and 23 never-depressed comparison participants (ND, 12 women, age 70 ± 8.02), matched on age and cognitive status. We employed a semi-automated procedure to segment the LC into three bilateral sections along its rostro-caudal extent, and calculated relative contrast as a proxy of integrity. Then, we examined associations between integrity and LLD diagnosis, age, and cognition, as measured via the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Delis-Kaplan Executive Function System (D-KEFS). We did not identify an effect of LLD diagnosis nor age on LC integrity, but exploratory canonical correlation analysis across the combined participant sample revealed a strong (Rc = 0.853) and significant multivariate relationship between integrity and cognition (Wilks’ λ = 0.03, F(84, 162.44) = 1.66, p = <.01). The first and only significant variate explained 72.83% model variance, and linked better attention and delayed memory performance, faster processing speed, and lower verbal fluency performance with higher integrity in the right rostral but lower integrity in the left caudal LC. Our results complement prior evidence of LC involvement in cognition in healthy older adults, and extend this association to individuals with LLD.

Keywords

• Major Depressive Disorder
• Late-life
• Neuromelanin-sensitive imaging
• Locus coeruleus
• Canonical correlation analysis