Late-Onset Depression Mimicking a Primary Psychiatric Disorder: Diagnostic Pitfalls in Sporadic Creutzfeldt-Jakob Disease

Human prion diseases are rare neurodegenerative disorders that typically present with rapidly progressive neurological decline. Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disorder characterized by rapidly progressive encephalopathy. Although classically presenting with cognitive decline and myoclonus, early manifestations may be predominantly psychiatric, particularly in older adults, leading to diagnostic delay. We report the case of a 75-year-old woman with no prior psychiatric history who initially developed late-onset depressive symptoms accompanied by behavioral changes and progressive cognitive impairment. Her condition deteriorated over several weeks, evolving into a confusional state with apraxia and agnosia. Initial neurological examination did not reveal myoclonus. Brain magnetic resonance imaging (MRI) demonstrated diffusion-weighted imaging (DWI) hyperintensity involving the basal ganglia with cortical ribboning. Electroencephalography (EEG) revealed generalized periodic sharp wave complexes. Cerebrospinal fluid (CSF) analysis was non-inflammatory, the 14-3-3 protein was positive, and the real-time quaking-induced conversion (RT-QuIC) assay was not performed due to limited local availability. During hospitalization, she progressed to akinetic mutism, generalized myoclonus, autonomic instability, and severe dysphagia, consistent with advanced sCJD. This case illustrates that isolated late-onset depression may represent an early manifestation of sCJD. In elderly patients presenting with rapidly progressive psychiatric symptoms and poor treatment response, prion disease should be considered. Timely multimodal evaluation, including MRI, EEG, CSF 14-3-3 protein, and RT-QuIC when available, is critical to support the diagnosis and prevent inappropriate psychiatric management.