Age-related differences in Rostral-Middle locus coeruleus microstructure: A critical role in cognitive decline revealed by magnetic resonance relaxometry

Abstract

Abstract Background The Locus Coeruleus (LC) is a critical brain region affected by neurodegenerative diseases and aging. Despite its importance, in-vivo investigations of age-related LC degeneration and association with cognitive decline have been limited. Method We employed magnetic resonance relaxometry, namely the Bayesian Monte-Carlo analysis of multicomponent driven equilibrium single pulse observation of T1 and T2 (BMC-mcDESPOT) MRI method, to estimate microstructural integrity represented by longitudinal (R1) and transverse (R2) relaxation rates, as well as Myelin Water Fraction (MWF) in the LC of a diverse cohort of 120 cognitively unimpaired individuals aged 22 to 94 years. BMC-mcDESPOT offers high spatial resolution and is effective for mapping detailed microstructural changes within the LC. We examined age-related differences in LC microstructure, their associations with cognitive changes, and the spatial variation of these microstructural changes within the LC, exploring their distinctive contributions to cognitive decline. Results LC-R2 values declined significantly with age, particularly in the rostral-middle regions. LC-R1 and LC-MWF values showed significant positive correlations with cross-sectional memory scores. Longitudinally, the rostra-middle LC-R2 values showed an age-moderated effect, with lower values predicting steeper memory decline at advanced ages. Conclusions Quantitative MR relaxometry reveals that LC microstructural integrity declines with age and is predictive of cognitive decline, particularly in memory. Our MR relaxometry biomarkers, especially in the rostral LC, serve as sensitive imaging biomarkers of early structural alterations and cognitive declines in aging.

Keywords

• Locus coeruleus
• MRI biomarker
• Relaxometry
• Aging
• Cognition