Quantification of ARIA During the Treatment of Alzheimer's Patients

Project Summary/Abstract Alzheimer’s disease is characterized by β-amyloid deposits and neurofibrillary tangles preceding neuronal loss and cognitive decline. The overall goal of this proposal is to detect and quantify treatment-related changes and abnormalities in Alzheimer patients’ brains using MR images while patients are undergoing amyloid clearing drug treatment. We will develop and validate the lesion detection and quantification software and deploy it as a clinically usable tool. Current detection of ARIA lesions depends on visual detection by trained radiologists. In recent years, multiple amyloid deposit modifying drugs have been developed and used in trials with Alzheimer's disease patients. During these drug trials, it is not uncommon that some patients developed imaging abnormalities in the brain and clinical symptoms. These amyloid-related imaging abnormalities (ARIA) manifest as intracerebral hemorrhage (ARIA-H), and vasogenic edema (ARIA-E). With the recent FDA approval of amyloid-targeting monoclonal antibody aducanumab in Alzheimer’s disease, brain imaging has become an indispensable tool to monitor the patients’ brains during therapy. The current recommendation on use of the amyloid clearing drug aducanumab is to have MRIs prior to initiating therapy, during the titration of the drug, and at any time the patient has symptoms suggestive of ARIA. It is recommended to have dose interruption or treatment discontinuation for symptomatic ARIA and moderate-severe ARIA. In addition, Cerebral Amyloid Angiopathy (CAA) patients also experience ARIA-like lesions in their brains and MRI is the recommended imaging modality to monitor the CAA progression. One would expect that in the near future amyloid deposit modifying drugs will be used in autosomal dominant AD, or other amyloid related diseases such as Levy body dementia concomitant with amyloid beta accumulation, or Down syndrome where amyloid plaques and symptoms of dementia develops later in midlife of the patients. Therefore, a treatment monitoring brain imaging software will have an important role in terms of patient care in a wider set of disease entities where patients are given amyloid clearing drugs.