Objective: We describe atypical motor and cognitive features in a case of familial Alzheimer disease (FAD) due to presenilin-1 (PS-1) mutation.
Background: Extrapyramidal signs (EPS) typically are a late-presenting feature of sporadic Alzheimer disease (AD), but relatively little data are available regarding EPS in FAD.
Method: A 59-year-old, right-handed man of Caribbean-Hispanic descent underwent brain imaging studies, laboratory tests for AD, and serial neurologic and neuropsychologic evaluations.
Results: The patient presented with recent-onset delusional ideation associated with cognitive decline. Prominent EPS developed soon after initiation of an atypical neuroleptic agent. Neuropsychologic evaluation revealed global cognitive deficits; he was found to be a carrier of a PS-1 point mutation at position G206A. EPS resolved completely after discontinuing the neuroleptic agent and coincided with improved motor speed, set initiation, and verbal fluency.
Conclusions: Severe neuroleptic sensitivity and associated deficits of cognitive speed occurred in response to a dopaminergic antagonist agent; both responded readily to withdrawal of the offending agent. Patients with PS-1 AD may be at substantially increased risk of neuroleptic-induced EPS. That feature underscores the heterogeneity of the FAD clinical phenotype.