Related Experiment Video
Updated: Jul 3, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Reduced diffusion associated with amyloid-related imaging abnormalities in three patients treated with donanemab
Nicholas U Schwartz1, Connor D Dietz1, Zoe Lin1
1Edward and Pearl Fein Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Abstract:
Amyloid-related imaging abnormalities (ARIA) with edema (ARIA-E) and with hemorrhage (ARIA-H) are common adverse effects of amyloid-targeting therapies (ATT), characterized on MRI by T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities and susceptibility-sensitive hypointensities, respectively. ARIA resulting from ATT is not commonly associated with reduced diffusion or acute infarcts. In this case series, we describe three patients with mild cognitive impairment due to Alzheimer's disease (AD) - a 75-year-old woman, a 74-year-old woman, and an 80-year-old man (APOE ε3/ε3, ε4/ε4, and ε3/ε4, respectively) - who developed ARIA accompanied by transient foci of reduced diffusion within the first six months of donanemab treatment, without permanent T2/FLAIR correlates. The diffusion-restricting lesions may represent ischemic infarcts, although the lack of permanent T2/FLAIR correlate is atypical. Clinicians should be aware that reduced diffusion may accompany ARIA. The course can be highly dynamic, and both the clinical presentation and management implications may vary.
Insights
Amyloid-related imaging abnormalities (ARIA) during donanemab treatment can show transient reduced diffusion, which is atypical. Clinicians should monitor for these dynamic changes in Alzheimer's disease patients.
Area of Science:
- Neurology
- Radiology
- Pharmacology
Background:
- Amyloid-targeting therapies (ATT) for Alzheimer's disease (AD) can cause amyloid-related imaging abnormalities (ARIA), including edema (ARIA-E) and hemorrhage (ARIA-H).
- ARIA typically presents as MRI T2/FLAIR hyperintensities or susceptibility-sensitive hypointensities and is not commonly linked to reduced diffusion or acute infarcts.
Purpose of the Study:
- To report a case series of patients experiencing ARIA with transient reduced diffusion during donanemab treatment for mild cognitive impairment due to AD.
- To highlight atypical MRI findings associated with ARIA in patients receiving amyloid-targeting therapies.
Main Methods:
- Case series describing three patients with mild cognitive impairment due to AD treated with donanemab.
- Analysis of MRI findings, specifically T2/FLAIR hyperintensities, susceptibility-sensitive hypointensities, and diffusion-weighted imaging, during ARIA events.
Main Results:
- Three patients developed ARIA with transient foci of reduced diffusion within six months of donanemab treatment.
- These diffusion-restricting lesions occurred without permanent T2/FLAIR abnormalities, which is atypical for ARIA.
- The observed diffusion changes may indicate transient ischemic infarcts, though their resolution without persistent MRI correlates is unusual.
Conclusions:
- Reduced diffusion can be a transient feature accompanying ARIA in patients undergoing donanemab therapy for AD.
- Clinicians must be aware of this potential association and the dynamic nature of ARIA presentation.
- The variable clinical presentation and management implications of ARIA with reduced diffusion require careful consideration.
