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Microhemorrhage Findings on Baseline Rosas MRI Data

H. Basselerie1, L. Bracoud2, H.M. Schneble3, S. Gouttard2, I. Guignot3, A. Istace2, F. Roche2, J. Schaerer2, M. Pueyo3, C. Pachai2, B. Vellas1, F. Bonneville1    1 CHU Toulouse, France  2 BioClinica, Lyon, France - email: luc.bracoud@bioclinica.com  3 Institut de Recherches Internationales Servier, Suresnes, France

INTRODUCTION

  • Cerebral microhemorrhages, although common among the elderly, are known to be related to the presence of amyloid in the brain, cognitive impairment and dementia severity.
  • This work assesses the prevalence of microhemorrhages in ROSAS, a monocentric observational study which includes normal controls as well as MCI and AD subjects.

METHODS

Population

  • The ROSAS study is a monocentric observational study which ran in Toulouse, France, and was designed to identify and evaluate the clinical usefulness of AD biomarkers by collecting samples from Normal Controls (NC), Mild Cognitive Impairment (MCI) and AD subjects, following them for up to 4 years.
  • Subjects aged 65 years or older were enrolled, including Normal Controls (NC, no memory complaints, MMSE≥26 and CDR=0), Mild Cognitive Impairment (MCI, MMSE≥24 and CDR=0.5, memory impairment based on RAVLT and who did not meet DSM IV criteria for AD dementia) and AD (12≤MMSE≤26 and CDR≥0.5 and meeting DSM IV criteria).

MRI Data

  • Susceptibility-Weighted (SWI) MRI scans were collected up to 3 times between Baseline and Month 48, at one site using a Philips Achieva 3T scanner, for consenting subjects (n=153, including 51 NC, 41 MCI and 61 AD).
  • 3DT1 data consisted of an axial VenoBOLD High-Resolution sequence with a 1x1x1 mm3 acquisition voxel size, reconstructed in each direction at ~ 0.5 mm.
  • Minimum Intensity Projection (minIP) reconstructed slices were centrally generated (6 mm thick, with 3 mm overlap).

Image review and analysis

  • Baseline SWI data (both native and minIP) were reviewed by one rater.
  • Bleeds were categorized by location and size, as follows:
    • Deep: deep gray matter (basal ganglia and thalamus) and white matter of the corpus callosum, internal, external, and extreme capsule
    • Lobar: cortical gray matter and subcortical or periventricular white matter
    • Infratentorial: brain stem and cerebellum
  • Bleeds were further classified by size, as being < 5 mm, between 5 and 10 mm (so-called large microhemorrhages) or > 10 mm.
  • Descriptive statistics were computed for each group.
  • Pearson Chi-Square tests were used to assess differences between groups.

RESULTS

  • Microhemorrhages (≤10mm) were reported on 56.9% NC, 68.3% MCI and 65.6% AD.
  • Only 2.0% NC had more than 4 microhemorrhages, as compared to 22.0% MCI and 11.5% AD.
  • Significant differences between groups were found for the presence of infratentorial microhemorrhages (p=0.035) and of >4 microhemorrhages (p=0.01), and between NC and non-NC for the presence of large microhemorrhages (p=0.045) and >4 lobar microhemorrhages (p=0.029).
  • Bleeds >10 mm were found on only 2 MCI and 2 AD.

CONCLUSIONS

  • A majority of ROSAS subjects from all clinical categories had ≥1 microhemorrhage.
  • Multiple (>4), multiple lobar (>4), large (5-10 mm in size) and infratentorial microhemorrhages were significantly more frequent in non-NC subjects.
  • Whether these findings could be a predictor for risk of conversion from MCI to AD will be investigated after the end of the study.

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