Alzheimer s & Dementia | 2019
SUBJECT FACTORS RELATED TO CSF DYNAMICS CONFOUND MEASUREMENT OF CSF BIOMARKERS IN ADNI
Abstract
MRI. In particular, Disproportionately Enlarged Subarachnoidspace 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 aB1-42, 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 andADbiomarker 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 CDESHwhile amyloid-PETand CSF ratiomeasures do not. References:1) N. Gunter et al https://doi.org/10. 1016/j.nicl.2018.11.015. P2-226 SUBJECT FACTORS RELATED TO CSF DYNAMICS CONFOUND MEASUREMENT OF CSF BIOMARKERS IN ADNI