Neus Falgàs, Marta Peña-González, Andrea Val-Guardiola, Agnès Pérez-Millan, Núria Guillén, Jordi Sarto, Diana Esteller, Beatriz Bosch, Guadalupe Fernández-Villullas, Adrià Tort-Merino, Gerard Mayà, Josep Maria Augé, Alex Iranzo, Mircea Balasa, Albert Lladó, Manuel Morales-Ruiz, Núria Bargalló, Emma Muñoz-Moreno, Lea T Grinberg, Raquel Sánchez-Valle. Alzheimer’s & Dementia.
ABSTRACT
INTRODUCTION Early-onset Alzheimer’s disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset Alzheimer’s disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage.
METHODS One hundred four subjects with AD diagnosis and 32 healthy controls were included. Participants underwent magnetic resonance imaging (MRI) to measure LC integrity, measures of noradrenaline levels in cerebrospinal fluid (CSF) and Neuropsychiatric Inventory (NPI). We analyzed LC-noradrenaline measurements and clinical and Alzheimer’s disease (AD) biomarker associations.
RESULTS EOAD showed higher NPI scores, lower LC integrity, and similar levels of CSF noradrenaline compared to LOAD. Notably, EOAD exhibited lower LC integrity independently of disease stage. LC integrity negatively correlated with neuropsychiatric symptoms. Noradrenaline levels were increased in AD correlating with AD biomarkers.
DISCUSSION Decreased LC integrity negatively contributes to neuropsychiatric symptoms. The higher LC degeneration in EOAD compared to LOAD could explain the more severe neuropsychiatric symptoms in EOAD.