Hippocampus-to-ventricle-ratio (HVR) as a novel biomarker for early diagnosis of Alzheimer disease (AD)

Abstract

As a progressive and irreversible disease, Alzheimer disease (AD) poses a serious health risk, as well as a heavy burden on caregivers, families, and society. Currently, AD cannot be cured, and the limited treatments available can only slow down the deterioration of symptoms. Therefore, diagnosis of AD in the preclinical stage is critical. Earlier diagnosis means a chance to slow down the disease at an earlier stage. However, AD has an insidious onset and can have a latent period of more than 10 years before symptoms appear. During this period, early onset biological markers of AD indexes can assist the diagnosis. Structural imaging studies have demonstrated that the medial temporal lobe (MTL) is where the pathology of AD first appears. A central structure in the MTL is the hippocampus. The hippocampus has a clear anatomical structure, providing a practical basis for its use as a brain imaging marker. There are a large number of studies that have found a relationship between hippocampal volume and cognitive function, and the development of AD. Due to large interindividual variability, its clinical use was so far limited. In this doctoral thesis, I used the hippocampal to ventricle ratio (HVR), and provided preliminary evidence that HVR is superior to pure hippocampal volume in indicating hippocampal integrity. Isummarized previous AD markers in my first review paper, and presented the advantages of HVR. This became the basis for my second cross-sectional study and my third longitudinal study. In the cross-sectional study, I directly compared three groups of subjects (healthy, early stage, advanced stage) and used HV or HVR as markers for the statistical analysis. The results suggested that HVR can distinguish differences between groups better than HV. In the longitudinal study, all subjects were healthy at the start of the MRI examination. Over time, some remained healthy, some started to develop AD, and some developed the full AD syndrome. Here too, the results showed that even when all subjects were in the asymptomatic “healthy” phase, HVR was able to show significant differences between the groups. In summary, HVR largely overcomes the disadvantages of pure hippocampal volume as a structural MRI marker for AD and its superiority and validity have been verified in this thesis. Although some important limitations are acknowledged, future studies should clarify whether this marker may also be useful in clinical practice.