SPATIAL DISTRIBUTION AND TOPOGRAPHICAL RELATIONSHIPS OF PATHOLOGY AND NEURODEGENERATION IN ALZHEIMER’S DISEASE

Abstract

dynamics can be obtained from T1-weighted MRI. In particular, Disproportionately Enlarged Subarachnoid-space Hydrocephalus (DESH), characterized by tight CSF spaces at the high convexity, ventriculomegaly and enlarged Sylvian fissures, is a strong marker of abnormal CSF dynamics. We have an automated method to detect these imaging features on T1-weighted MRI; i.e. a “computational DESH” or CDESH score (Figure 1). Using CDESH as a surrogate measure of altered CSF dynamics we investigate if it helps explain discrepancies between CSF and PET biomarkers of amyloid in the ADNI cohort. Methods: CDESH scores for baseline MRI from 843 ADNI-G0/2 participants with CSF assays for aB142, pTau, tTau and AV45-SUVR were calculated. CDESH+ and CDESHgroups were defined (Figure 2). We tested the hypothesis that the group-wise distributions of each biomarker were consistent using an empirical Kolomogorov-Smirnov test. Results: Baseline demographics and AD biomarker results, divided by diagnostic group, is shown in Table 1. Seven percent of participants were CDESH+. Distributions of CSF ab1-42, pTau, and tTau, were significantly inconsistent between groups (Figure 3). The distributions for AV45 were not significantly inconsistent between groups (Figure 4). In a subsample (N1⁄4143 participants) CSF Ab 1-40 and 1-42 values were available: the 42:40 ratio distributions are not significantly inconsistent between groups. The ratio of pTau to Ab1-42 was not significantly inconsistent between groups. Thirty percent of CDESH+ participants have low CSF Ab1-42 and low AV45 (i.e. discordant markers), different than the 10% of CDESHparticipants (Yates-corrected ratio test p<0.001) (Figure 5). MMSE and CDR sum-of-boxes distributions did not differ between groups. Conclusions: Participants with high CDESH scores have structural imaging consistent with alterations in CSF dynamics. Consistent with our hypothesis that subject-factors related to CSF dynamics influence discrepancies between CSF and imaging biomarkers of amyloid, unnormalized CSF biomarkers differ in participants with and without CDESH while amyloid-PET and CSF ratio measures do not. References:1) N. Gunter et al https://doi.org/10.1016/ j.nicl.2018.11.015. IC-P-079 SPATIAL DISTRIBUTION AND TOPOGRAPHICAL RELATIONSHIPS OF PATHOLOGYAND NEURODEGENERATION INALZHEIMER’S DISEASE