A systematic review of locus coeruleus degeneration detected by neuromelanin sensitive MRI technique in patients with Alzheimer’s disease

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AbstractBackgroundThe locus coeruleus(LC) is a bilateral nucleus located in the dorsal pontine tegmentum and is the major source of noradrenaline(NA), which plays a key role in cognition. While cognitive decline in Alzheimer disease(AD) has primarily been related to dysfunction within the cholinergic system in the nucleus basalis, there is considerable research evidence indicating extensive LC degeneration in AD, with some suggesting that it is among the earliest pathologies. Therefore, the early vulnerability of the LC to AD is of considerable clinical significance, as this raises the possibility that changes of the LC activity may provide early detection markers for diagnosis as well as early intervention targets to delay AD progression. However, the contribution of LC degeneration to cognitive decline in the development of AD has been underappreciated due to methodological difficulties, with most evidence coming from animal and post‐mortem studies. The absence of reliable non‐invasive direct measures of the LC remains the biggest challenge. Recent research indicates that LC visibility is driven by neuromelanin content of noradrenergic neurons and the intrinsic neuromelanin‐sensitive MRI technique enables direct visualisation of the LC.MethodsA systematic search of the literature was performed on electronic databases including PubMed, Web of Science, and Embase. Human imaging studies employing neuromelanin‐sensitive MRI technique to measure LC degeneration were included in this review. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews.ResultsLC‐contrast ratio or LC‐signal intensity detected by the neuromelanin‐sensitive MRI were found to be significantly reduced in patient groups with Alzheimer's disease compared with the healthy control group in all included studies, with recent evidence indicating its significant association with levels of CSF amyloid.ConclusionsThe current systematic review strongly supports the use of the neuromelanin‐sensitive MRI technique to detect the LC degeneration as a biomarker for AD neuropathology. Future research are warranted to characterize how LC signals evolve at different stages of AD, which could lead to novel intervention approaches to delay or prevent cognitive decline.