To determine the relationship between regional brain edema caused by anti-amyloid monoclonal antibody therapy (ARIA-E) and the degree of regional β-amyloid (Aβ) positron emission tomography (PET) signal reduction.

Although ARIA has been attributed to an exacerbation of amyloid angiopathy, the transient nature of ARIA-E suggests that less severe vascular changes may also be at work. If these changes are related to the removal of Aβ, it could be postulated that greater Aβ removal occurs in areas with ARIA-E.  To test this hypothesis, we used PET to measure the regional density of Aβ before ARIA-E occurred and after ARIA-E had been resolved.

In patients with moderate or severe ARIA-E after lecanemab therapy, we quantified the regional degree of ARIA-E on FLAIR MRI and the regional Aβ level with PET, both at baseline, pre-lecanemab therapy, and after ARIA-E had cleared, as documented on FLAIR MRI. Aβ level was expressed as Standard Uptake Value Ratio (SUVR), with whole cerebellum as region of reference. The statistical significance of SUVR change (Δ) within each subject across 40 brain regions was calculated using the Mann-Whitney U test.

Five patients (age 74.4 ± 5.4 years, 4 women) had moderate or severe ARIA-E. Except one patient, with a small ARIA-E region and a marked global Aβ decrease in the follow up PET, all others had a statistically significant greater Aβ PET signal decrease in regions with ARIA-E.

Greater regional Aβ PET signal reduction in areas involved by ARIA-E may reflect enhanced local Aβ clearance, reduced tracer binding site availability, impaired glymphatic flow from immune complex deposition, or other mechanisms. Our finding refines the characterization of ARIA-E and raises the possibility that its occurrence may have beneficial as well as adverse implications.