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Background
Alzheimer’s Disease (AD) is a progressive neurodegenerative process associated with the build-up of beta-amyloid plaques and neurofibrillary tangles throughout the brain and is a leading cause of morbidity and mortality in older individuals. Imaging has an important role in diagnosis and prognosis of AD. Recently, the FDA has approved several new medications for the treatment of AD (i.e., aducanumab, donanemab, and lecanemab). With the advent of disease-modifying drugs, the role of radiologists in the management of AD will evolve to focus on improved/early diagnosis and monitoring of treatment outcomes.

Educational Goals / Teaching Points
We aim to educate radiologists on the current role of imaging in the assessment of AD. Through a case-based approach, we will demonstrate the classic findings related to AD, early-onset AD, and pertinent variants in a variety of modalities. Finally, we will discuss the novel treatments recently approved by the FDA and pertinent imaging findings corresponding to treatment effects.

Key Anatomic/Physiologic Issues and Imaging Findings/Techniques
MRI in the work up of neurodegenerative disorders is primarily limited to evaluating degree and pattern of volume loss. In classic AD, the classic finding is volume loss affecting the precuneus (leading to prominence of the parieto-occipital sulcus and marginal ramus of the cingulate sulcus), posterior cingulate gyrus, and hippocampi (in advanced disease). FDG-PET is a useful adjunct to structural imaging, given its ability to demonstrate metabolic neurodegenerative changes, often years before parenchymal loss becomes apparent. PET demonstrates decreased FDG avidity in the precuneus, parietal/temporal lobe, and posterior cingulate gyrus. Amyloid-binding PET agents (i.e., F-18 Florbetapir) are also useful for assessing extent of amyloid deposition throughout the brain, a prerequisite for AD. White matter will demonstrate normal uptake of Florbetapir, but increased uptake within the cortical gray matter correlates with AD risk. Finally, new amyloid-specific binding therapies have been shown to be effective in reducing amyloid burden in the brain and decreasing rate of cognitive decline in AD. These treatments, however, can result in important though often asymptomatic side effects that are detectable by MRI, known as amyloid-related imaging abnormalities (ARIA). ARIA is categorized into edematous/effusion-related changes (ARIA-E) and hemorrhagic changes (ARIA-H). These findings are critical for treatment decisions and put the burden on radiologists to help ensure that patients are treated correctly.

Conclusion
Radiology plays a crucial role in the assessment of AD. With the advent of novel therapies for AD, the role of radiology will continue to expand into the management, diagnosis, prognosis, and treatment follow up of patients. As such, it is imperative for radiologists to understand the unique contributions of varying imaging modalities to ensure proper diagnosis, evaluation, and management.