Progressive fetal infection/inflammation is strongly associated with neural injury after preterm birth. We aimed to test the hypotheses that progressively developing fetal inflammation leads to neuroinflammation and impaired white matter development and that the histopathological changes can be detected using high-field diffusion tensor magnetic resonance imaging (MRI). Chronically instrumented preterm fetal sheep at 0.7 of gestation were randomly assigned to receive intravenous saline (control; n = 6) or a progressive infusion of lipopolysaccharide (LPS, 200 ng intravenous over 24 h then doubled every 24 h for 5 days to induce fetal inflammation, n = 7). Sheep were killed 10 days after starting the infusions, for histology and high-field diffusion tensor MRI. Progressive LPS infusion was associated with increased circulating interleukin (IL)-6 concentrations and moderate increases in carotid artery perfusion and the frequency of electroencephalogram (EEG) activity (p < 0.05 vs. control). In the periventricular white matter, fractional anisotropy (FA) was increased, and orientation dispersion index (ODI) was reduced (p < 0.05 vs. control for both). Histologically, in the same brain region, LPS infusion increased microglial activation and astrocyte numbers and reduced the total number of oligodendrocytes with no change in myelination or numbers of immature/mature oligodendrocytes. Numbers of astrocytes in the periventricular white matter were correlated with increased FA and reduced ODI signal intensities. Astrocyte coherence was associated with increased FA. Moderate astrogliosis, but not loss of total oligodendrocytes, after progressive fetal inflammation can be detected with high-field diffusion tensor MRI.

Background Secondary prevention trials in cognitively‐normal older people with brain amyloid beta (Aβ) accumulation are emerging as the next frontier in dementia therapy. The A4 Study is an international randomised placebo controlled trial of immunotherapy against Aβ, a hallmark contributing factor to Alzheimer’s disease (AD). Here we report the screening characteristics and common reasons for participation and screen failure for the Melbourne Composite Site (MCS). Method An advertising campaign was conducted over three years. Individuals who expressed interest were phone screened for initial eligibility and invited to the MCS for full assessment. Cognitively normal [CDR=0; Logical Memory Index II (LMII) score 6 to 18; MMSE ≥25] individuals underwent Aβ‐PET imaging using Florbetapir and were classified as Aβ+ (eligible), or Aβ‐ (not eligible) according to study protocol. Participants also provided responses to the Concerns about AD (CAD) and Views and Perceptions of Amyloid Imaging (VPAI) questionnaires. Result Science media was our main recruitment source (Mastwyk M et al, International Psychogeriatric Association 2019, DOI: https://doi.org/10.1017/S1041610219000474). 689 individuals were invited to be screened for eligibility and 674 were enrolled. 51% were female and median education level was 16 years (IQR: 12 – 18); 336/517 (65.0%) reported a family history of dementia. 446/524 (85%) wanted to know if they would develop AD (CAD). 452/523 (87%) desired to contribute to AD research (VPAI). The main screen fail reasons in 580 participants were: classified as Aβ‐ (56%); CDR and/or LMII (11%); unstable medical condition (8%); MMSE <25 (4%); PET scans were acquired in 431 participants; 94 Aβ+ participants were randomised [median age 70 (IQR: 67 – 73)]. Aβ‐ participants were more likely to be ≤70 years old. Conclusion Intervention trials in preclinical AD present a unique opportunity to reduce the impact of dementia for the future. Individual choice to participate in this sample was motivated by a desire to contribute to AD research and to find out their likelihood of developing AD.