Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease

Abstract

Early-onset Alzheimer disease (EOAD) diagnosis often represents a challenge because of the high frequency of atypical presentations. Our aim was to describe the clinical features, APOE genotype, and its pathologic correlations of neuropathologic confirmed EOAD. Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD (<60 years). Forty cases were selected. Mean age at onset was 54.5 years (range 46-60). The mean disease duration was 11 years with a mean diagnostic delay of 3.1 years. A total of 37.5% had a nonmemory presentation. Behavioral/executive dysfunction was the most prevalent atypical presentation. Incorrect initial clinical diagnoses were common (53%) in patients with atypical presentations, but rare when anterograde amnesia was the presenting symptom (4%). The incorrect initial clinical diagnoses were 2 behavioral variant frontotemporal lobar degeneration, 2 normal pressure hydrocephalus, 1 semantic dementia, 1 primary progressive aphasia, 1 corticobasal degeneration, 1 pseudodementia with depression, and 1 unclassifiable dementia. APOE genotype was ε3/ε3 in 59%, with no significant differences between typical and atypical presentations. APOE ε4 was 3.3 times more frequent in subjects with family history of AD. A total of 97.5% of the cases presented advanced neurofibrillary pathology. A total of 45% of the patients had concomitant Lewy body pathology although localized in most cases and without a significant clinical correlate. One third of patients with pathologic confirmed EOAD presented with atypical symptoms. Patients with EOAD with nonamnestic presentations often receive incorrect clinical diagnoses.