Nonmemory Symptoms Can Lead to Misdiagnosis in Early-Onset Alzheimer Disease

Although the autosomal dominant form of early-onset Alzheimer disease (AD; onset at or before age 60) is often recognized because of family history, sporadic cases are less frequently identified in the early stages of the illness. In a retrospective case review of 40 patients with autopsy-proven early-onset AD (age range, 46–60; mean age, 54; mean duration of illness, 11 years), researchers highlight diagnostic pitfalls in this subpopulation. Clinical histories were provided by the diagnosing clinicians who had managed the patients during their illness. Pathologic assessments and genetic testing for APOE alleles were conducted in autopsy specimens.

Overall, 62% of patients presented with typical episodic memory dysfunction, and 38% first presented with predominantly nonmemory symptoms, including frontal dysfunction (behavioral dyscontrol, executive dysfunction, or both); language deficits; or posterior variants (visuospatial dysfunction, praxis deficits, or both). Regardless of the presenting symptoms, mean delay to diagnosis was 3.1 years. Initial clinical misdiagnoses were made in 53% of patients with atypical presentations and 4% of patients who presented with memory deficits. Final clinical misdiagnosis rates remained significantly different (atypical, 47%; typical, 4%). Patients with family histories of AD were more than three times as likely as those without such histories to carry APOE*E4 alleles; however, APOE status had no significant relation to clinical presentation.