Optimal Cut-Off Value for Locus Coeruleus-to-Pons Intensity Ratio as Clinical Biomarker for Alzheimer's Disease: A Pilot Study

Background: Studies using neuromelanin-sensitive-MRI have established the locus coeruleus (LC)-to-pons intensity ratio as a biomarker for diagnosis of Parkinson's and Alzheimer's diseases. More detailed analysis is needed for exploiting the highest clinical potential of this technique. Objective: The aim is to determine the location of the highest LC-to-pons ratio within the LC and develop an easy-to-use tool for clinical application. Methods: Ten patients diagnosed with various stages of Alzheimer's disease (74.1 +/- 3.9 years, range 68-80, 7 females) and ten healthy elderly subjects (72.4 +/- 3.1 years, range 68-77, 5 females) participated in the study. Five subsequent slices with a thickness of 2.5 millimeters were analyzed using the image analysis tool FSL, starting with the first slice below inferior colliculus. The outcome variable was the intensity ratio between maximum values of LC and adjacent pontine region. Results: The section located 10 millimeters below the inferior colliculus has the highest potential in differentiating between healthy controls and patients, with the intensity-ratio difference between groups of 12.3% and effect size of 1.577. For the cut-off value of 1.09, the sensitivity and specificity values were 100% and 80%, respectively. Conclusion: We consider the method a promising clinical tool to aid AD diagnosis workup.