Initial Experiences with Amyloid-Related Imaging Abnormalities in Patients Receiving Aducanumab Following Accelerated Approval.

Aducanumab is the first FDA-approved amyloid-lowering immunotherapy for Alzheimer's disease. There is little real-world data to guide management of amyloid-related imaging abnormalities (ARIA), a potentially serious side-effect which requires surveillance with magnetic resonance imaging. We report our experiences in managing ARIA in patients receiving aducanumab at the Butler Hospital Memory and Aging Program during the year following FDA approval. We followed the Appropriate Use Recommendations for aducanumab to guide patient selection, detection, and management of ARIA (1). ARIA-E occurred in 6 out of 24 participants treated; all APOE-ε4 carriers. Treatment was discontinued in 4 cases of moderate-severe ARIA-E, temporarily held in 1 moderate case, and dosed through in 1 mild case (mean duration = 3 months, range, 1-6 months). No participants required hospitalization or high dose corticosteroids. Participants on anticoagulation were excluded and no macrohemorrhages occurred. These data support the measured approaches to treatment outlined in the Appropriate Use Recommendations.

Metabolic patterns and insulin responsiveness of enlarging fat cells.

The rate and pattern of glucose metabolism, basal lipolysis, and intracellular concentration of free fatty acids were determined in isolated epididymal fat cell preparations (mean volume 30-800 pl) from rats on the basis of fat cell number and in relation to the cell volume. The effects of increasing glucose concentrations in the medium and of insulin on the cellular metabolic activities were compared. Expanding fat cell volume correlated positively and significantly (P < 0.001) with the synthesis of glyceride glycerol from glucose (correlation coefficient, r = 0.919), with rates of basal lipolysis (r = 0.663), and with intracellular free fatty acid accumulation (r = 0.796); it correlated negatively and significantly with glucose conversion to glyceride fatty acids (r = -0.814, P < 0.01). The differences in patterns of glucose metabolism and basal lipolysis between small (<100 pl) and large (>400 pl) fat cells were not modified by insulin or by increments in glucose concentration. The results indicate that the reduced capacity of the large fat cells to respond to insulin cannot be attributed solely to a limited capacity of the cells to take up and metabolize increasing amounts of glucose. The acquired unresponsiveness of the large cells to insulin may result from an alteration in the mechanism of action of insulin and may be related to an intracellular metabolic derangement with increased basal lipolysis, free fatty acid accumulation, and accelerated glyceride synthesis resulting from the accumulation of triglyceride.