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Andrew E. Beaudin

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YNICL Journal 2022 Journal Article

Diffusion tensor tractography of the fornix in cerebral amyloid angiopathy, mild cognitive impairment and Alzheimer’s disease

  • Ibrahim Shaikh
  • Christian Beaulieu
  • Myrlene Gee
  • Cheryl R. McCreary
  • Andrew E. Beaudin
  • Diana Valdés-Cabrera
  • Eric E. Smith
  • Richard Camicioli

PURPOSE: Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls. METHODS: Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI. RESULTS: Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was ∼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group. CONCLUSION: There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.

YNICL Journal 2020 Journal Article

Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy

  • Cheryl R. McCreary
  • Andrew E. Beaudin
  • Arsenije Subotic
  • Angela M. Zwiers
  • Ana Alvarez
  • Anna Charlton
  • Bradley G. Goodyear
  • Richard Frayne

OBJECTIVES: To test the hypotheses that peak skeletonized mean diffusivity (PSMD), a measure of cerebral white matter microstructural disruption, is 1) increased in patients with cerebral amyloid angiopathy (CAA) compared to normal control (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD); 2) associated with neuropsychological test performance among CAA patients; and 3) increased more quickly over one year in CAA than in AD, MCI, and NC. METHODS: Ninety-two participants provided a medical history, completed a neuropsychological assessment, and had a magnetic resonance (MR) exam including diffusion tensor imaging (DTI) from which PSMD was calculated. A 75-minute neuropsychological test battery was used to derive domain scores for memory, executive function, and processing speed. Multivariable analyses controlling for age and sex (and education, for cognitive outcomes) were used to test the study hypotheses. RESULTS: /s) groups (p < .01). Among CAA patients, higher PSMD was associated with slower processing speed (estimated -0.22 standard deviation (SD) change in processing speed z score per SD increase in PSMD, 95% CI -0.42 to -0.03, p = .03), higher WMH volume [β = 0.74, CI 0.48 to 1.00], and higher CAA SVD score [β = 0.68, CI 0.24 to 1.21] but was not associated with MMSE, executive function, memory, CMB count, or cortical thickness. PSMD increased over 1-year in all groups (p < .01) but without rate differences between groups (p = .66). CONCLUSIONS: PSMD, a simple marker of diffuse global white matter heterogeneity, is increased in CAA. Our findings further support a role for white matter disruption in causing cognitive impairment in CAA.