Elevated locus coeruleus metabolism provides resilience against cognitive decline in preclinical Alzheimer's disease

Abstract

INTRODUCTION: Alterations in locus coeruleus’ (LC) metabolic turnover are associated with Alzheimer's disease (AD)-pathology and cognitive impairment. However, the evolution of these changes across disease stages and their functional relevance remains unknown. METHODS: We examined associations of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) -derived LC metabolism with clinical diagnostic status, cerebrospinal fluid (CSF) -based AD biomarkers of AD pathology, and cognitive decline in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (n = 604). RESULTS: FDG-PET-derived LC metabolism was elevated in the earliest preclinical stages and lower in later disease stages. Higher LC metabolism was associated with attenuated memory decline in preclinical stages, particularly in those with low CSF Aβ42, but not in AD patients with cognitive impairment. DISCUSSION: Higher locus coeruleus [18F]-FDG-PET-derived signal in the early preclinical stages of AD can confer cognitive resilience and may reflect increased metabolic activity, whereas later stages are characterized by lower LC FDG-PET-derived signal, possibly due to neurodegeneration. Highlights: LC FDG-PET signal is lower in Alzheimer's disease (AD) patients. LC FDG-PET signal is higher in the preclinical stage of AD. We observed less memory decline in those with higher LC FDG-PET signal. Higher LC FDG-PET signal conferred cognitive resilience in preclinical AD.