134 - Could Hippocampus Shape Be a Reliable Non-invasive Biomarker of Alzheimer Disease in down Syndrome?

Poster Board Number: 134
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Abstract Body : Introduction & Objectives: Intellectual disability, premature aging and Alzheimer’s disease dementia (ADd) caused by trisomy in chromosome 21 are among the main clinical issues associated with Down syndrome (DS). Although biomarkers such as cerebrospinal fluid and plasma extraction are commonly used for Alzheimer’s diagnosis, this method is invasive and difficult to apply in patients with DS. Moreover, early stages of ADd in individuals with DS are difficult to detect because dementia symptoms are confounded with the intellectual disabilities associated with DS. Consequently, ADd diagnosis in patients with DS remains challenging and alternative biomarkers of AD are needed. Brain biomarkers are promising, since patients with AD display enlarged lateral ventricles and grey matter atrophy, as well as dysmorphic hippocampus. These brain structures are also primarily affected in DS. The aim of this study is to test whether the shape of the hippocampus could be a reliable non-invasive biomarker for early detection of ADd in DS.
Materials and Methods: Structural MR scans (T1) from 167 individuals with DS and euploid controls were studied, including euploid controls (N=117, mean age 52 years); individuals with DS and no dementia (N=32, mean age 36 years); at prodromal stage of ADd (N=11, mean age 42 years); and diagnosed with ADd (N=7, mean age 51 years). Once the hippocampus was segmented and the corresponding mesh generated using the FSL tools for brain imaging data, a set of landmarks and semilandmarks (N=92) was measured semi-automatically for the entire sample using Viewbox 4. After the semilandmarks were slid to gain geometric homology, all hippocampi were superimposed by Procrustes analysis to get rid of orientation, location and scale differences. Statistical comparisons between groups were performed with R, Past, and MorphoJ.
Results: Hippocampus atrophy was detected in individuals with DS, with significantly reduced volumes in comparison to euploid individuals. Hippocampus volume and age had a significant effect on hippocampus shape, and respectively explained 11% and 5% of hippocampus shape variation (p< 0.0001), with both factors being significantly correlated among them (R²=0.1784; p< 0.0001). After removing age and size effects, we found that the shape of the hippocampus was significantly different between euploid and DS individuals with or without ADd. Interestingly, DS individuals asymptomatic for dementia displayed a significantly different hippocampus shape when compared with DS individuals diagnosed with ADd. In individuals with advanced dementia, the hippocampus was thinner in the mediolateral direction and displayed shape changes in both the head and tail, leading to a less concave hippocampal shape.
Conclusion: Our results reveal a link between the shape of the hippocampus and the neuropathologies related with DS and AD. Further research with larger samples should confirm the potential of morphological traits as reliable non-invasive biomarkers for ADd in DS.
Significance: The shape of the hippocampus is a promising non-invasive biomarker of Alzheimer disease in Down syndrome.