While episodic memory impairment remains the hallmark presentation of Alzheimer’s disease, a subset of patients initially present with non-amnestic cognitive changes that may delay recognition and diagnosis. In the primary care setting, these symptoms may go unrecognized and many patients are not diagnosed until mild-to-moderate stage dementia.1 Atypical presentations are particularly common in younger-onset cases, whereas older patients may have symptoms wrongfully attributed to normal aging or masked by comorbidities.2 Additionally, many providers lack confidence in distinguishing normal aging from mild cognitive impairment (MCI).3 Failure to recognize these variants contributes to delayed diagnosis and missed opportunities for early intervention with disease-modifying therapies.1
Atypical AD presentation has been largely linked to quantitative regional disparities in the distribution of plaques and/or tangles, neuropathological comorbidities, and multiple intrinsic characteristics ranging from affect resilience to genetic background.2 Posterior Cortical Atrophy (PCA), characterized by progressive visuospatial dysfunction, affects patients who struggle with depth perception and object perception.4 Recent studies have shown that language is intricately intertwined with visuospatial processing.4 The logopenic variant primary progressive aphasia (lvPPPA) presents with word-finding difficulty and difficulty understanding longer sentences; early non-verbal symptoms include difficulty with hearing in noise, route-finding, and memory.5
The behavioral variant of Alzheimer disease (bvAD) represents another important non-amnestic presentation. Patients with bvAD may show more severe behavioral symptoms than typical AD but remain less severe compared with behavioral variant frontotemporal dementia (bvFTD).6 Cognitively, patients with bvAD demonstrate worse executive performance than those with typical AD, while memory performance falls between typical AD and bvFTD.6 Neuroimaging has shown two phenotypes: an AD-like pattern with relative frontal sparing and a bvFTD-like pattern with posterior and anterior involvement, indicating that bvAD is clinically most similar to bvFTD while sharing pathophysiological features with typical AD.6
Recognition of these presentations requires comprehensive and timely evaluation that extends beyond memory testing to assess executive function, language, and visuospatial abilities.7 To aid in early detection of Alzheimer’s disease, machine learning integration into existing electronic health records data offers emerging promise.8 Clinicians who maintain awareness of Alzheimer’s phenotypic diversity ensure that non-amnestic presentations do not result in diagnostic delay or exclusion from appropriate treatment pathways.
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