Atypical Presentations of Alzheimer Disease

This article provides a comprehensive review of the distinct features of four atypical Alzheimer disease (AD) variants: dysexecutive AD, behavioral variant AD, posterior cortical atrophy, and the logopenic variant of primary progressive aphasia. It also elucidates their clinical presentations, underlying pathophysiologic pathways, diagnostic indicators, and management requirements.

Recent research has revealed that these atypical AD forms vary not only in clinical manifestations but in their functional neuroanatomy spanning a common pathophysiologic spectrum. Imaging techniques, such as MRI, fludeoxyglucose positron emission tomography (FDG-PET), and tau PET, have identified distinct abnormalities in specific brain regions associated with each variant. This same variability is less tightly coupled to amyloid imaging. Emerging diagnostic and therapeutic strategies should be tailored to each variant's unique features.

Atypical forms of AD often present with symptoms that are predominantly nonmemory related, distinguishing them from the more common memory-centric presentation of the disease. Two distinct clinical and pathologic entities, dysexecutive AD and behavioral variant AD, have replaced the outdated term frontal AD. Posterior cortical atrophy is another variant that mainly affects higher-order visual functions, which can lead to misdiagnoses because of its atypical symptom profile. Logopenic primary progressive aphasia is marked by difficulties in word retrieval, a challenge that may not be readily apparent if the person compensates by using circumlocution. Modern diagnostic techniques, such as MRI, PET, and biomarker analysis, have proven crucial for the accurate diagnosis and differentiation of these atypical AD variants. In treating these forms, it is critical to use tailored therapeutic interventions that combine pharmacotherapy with nonpharmacologic strategies to effectively manage the disease.