As rapidly progressive dementia (RPD), general paresis and Creutzfeldt-Jakob disease (CJD) may have overlapping clinical presentation due to a wide variety of clinical manifestations.

A 57-year-old man presented with rapid progressive cognitive decline, behavioral change, ataxic gait, tremor and pyramidal signs for 3 months. In addition to these multiple systemic involvements, positive result for the cerebrospinal fluid (CSF) 14-3-3 protein tentatively diagnosed him as probable CJD. However, due to increased serum rapid plasma reagin, venereal disease research laboratory, and fluorescent treponemal antibody-absorption reactivity in CSF, the final diagnosis was changed to general paresis.

A patient with RPD needs to be carefully considered for differential diagnosis, among a long list of diseases. It is important to rule out CJD, which is the most frequent in RPD and is a fatal disease with no cure. Diagnostic criteria or marker of CJD, such as 14-3-3 protein, may be inconclusive, and a typical pattern in diffusion-weighted imaging is important to rule out other reversible diseases.