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• W2896949575 abstract "Neuroinflammation is a well-recognized, but still poorly understood, pathological feature of AD from the earliest stages. Diffusion basis spectrum imaging (DBSI) has been developed and validated to detect and quantify white matter neuroinflammation in multiple sclerosis and spinal cord injury, and more recently applied to AD. Neuroinflammation could contribute to both the pathogenesis and treatment of AD and a reliable approach to analyze DBSI-derived neuroinflammation with reference to a normal population is desirable for its use in clinical AD trials. Here, we express neuroinflammation levels in preclinical and AD subjects with reference to a “normal” population, as Z-scores, as an approach to assess disease-specific neuroinflammation in AD. The DBSI method has been described previously (Wang et al., 2015, 2016). The normative reference population comprised 126 amyloid-negative, healthy cognitively normal (CN) subjects (age range=50-77yrs). We assessed 34 preclinical AD (PC; cognitively normal but amyloid positive) and 49 amyloid-positive subjects with a CDR=0.5 (CDR0.5; age range=50-77). DBSI cell ratio (CR; measuring severity of inflammatory cell infiltration) was quantified within 27 major white matter tracts generated from FSL. Tract-specific linear models predicting the dependence of CR on age were built using the reference population. In the reference population, 37% (10/27) of all white matter tracts showed a significant inverse relationship (p<0.05, uncorrected) between neuroinflammation and age, with age explaining 4-20% of the variance in CR. Statistically significant differences in CR between PC and CDR0.5 groups, using either raw or normed CR values, were observed in the fornix, anterior limb of the internal capsule, anterior and superior corona radiate, superior fronto-occipital and uncinate fasciculi. After Z-norming raw CR values, the body of the corpus callosum and cingulum also became statistically different between groups, while the genu of the corpus callosum, superior longitudinal fasciculus and external capsule were no longer statistically different. DBSI is an MRI-based approach to assess neuroinflammation. Referencing to a normal population provides a means of anchoring the signal so as to determine ‘abnormal’ CR levels as a measure of neuroinflammation, independent of effects of normal aging. This analysis strategy should be extended to grey matter . Uncorrected p-values of the t-tests between preclinical and CDR0.5 group cell ratios using normed CR (Z-scores) vs raw CR values. Pink tracts show no group difference in CR, whereas purple tracts show statistical differences, using both raw and normed values. In blue are tracts for which there was a statistical group difference using raw values, but no longer using normed values. In green are tracts for which there was no statistical group difference using raw values, but only when using normed values." @default.
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• W2896949575 date "2018-07-01" @default.
• W2896949575 modified "2023-10-16" @default.
• W2896949575 title "P3‐343: AGE‐NORMED DIFFUSION BASIS SPECTRUM IMAGING (DBSI) CELL RATIOS TO ASSESS NEUROINFLAMMATION IN ALZHEIMER'S DISEASE CLINICAL TRIALS" @default.
• W2896949575 doi "https://doi.org/10.1016/j.jalz.2018.06.1704" @default.
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