SPONTANEOUS ARIA WITH EDEMA AND MICROHEMORRHAGES IN A COGNITIVELY NORMAL SUBJECT FROM ADNI

Abstract

Amyloid-Related Imaging Abnormalities (ARIA) include sulcal effusions and edema (ARIA-E) on fluid attenuated inversion recovery (FLAIR) and superficial siderosis and microhemorrhages (ARIA-H) on T2* gradient recalled echo (GRE) images. The risk factors for ARIA-E are higher dosage of amyloid-modifying immunotherapy, carrying the APOE ԑ4 allele, increased clearance of amyloid-β protein, and presence of ARIA-H. Risk factors for ARIA-H are cerebral amyloid angiopathy, cardiovascular risk factors, experiencing a cerebrovascular event, and presence of ARIA-E. Observation of spontaneous ARIA in individuals who are not receiving amyloid-modifying treatment is rare. Our objective is to identify the risk of spontaneous ARIA in subjects in the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) cohort. The ADNI2/GO studies have a total of 1006 subjects with a range of diagnoses: cognitively normal, early mild cognitive impairment (MCI), late MCI, Alzheimer's disease, and significant memory concerns. The subjects have been followed since the start of ADNI2/GO in 2004, with a total of 3385 scans acquired and assessed until a spontaneous ARIA case was identified. The case was an 81-year-old, cognitively normal male who showed MRI evidence of spontaneous ARIA-E on FLAIR images and ARIA-H on T2* GRE images. As a volunteer in the ADNI2 study, he had four serial MRIs for 2 years and had no ARIA until the most recent visit. The findings were identified in the posterior left temporal lobe on MRI during the year 2 visit. The patient was not receiving amyloid-modifying therapy and the APOE genotype was ԑ3/ԑ3. The global amyloid SUVR on PET at time of MRI was 1.85 (positive), with a focal increased uptake in the left temporal-occipital lobe. ARIA-E and associated ARIA-H can be observed in cognitively normal elderly who do not carry the APOE ԑ4 risk allele, have no prior microhemorrhages, and are not receiving amyloid-modifying treatments. This is an important consideration when assessing MRI images for safety in amyloid-modifying clinical trials. Focal amyloid deposits around the region of ARIA-H suggest cerebral amyloid angiopathy may be responsible for the occurrence of ARIA in this case.