Prion disease masquerading as Alzheimer's disease

With the realistic prospect of disease modifying therapy, accurate and early diagnosis of Alzheimer's disease is increasingly important. Although prion diseases are classically recognised as rapidly progressive multi-focal dementias associated with other neurological features such as ataxia, myoclonus and visual symptoms, their clinical manifestations are remarkably heterogeneous. The very rapid clinical decline that typically prompts consideration of Creutzfeldt-Jakob disease is not seen in some atypical sporadic cases, nor in most inherited prion diseases. In some cases these may have disease durations and clinical presentations that are similar to those of Alzheimer's disease. We report 5 case studies and clinical data from the National Prion Monitoring Cohort (a longitudinal observational study into all forms of prion disease in the UK which has been enrolling patients since October 2008). Of 188 consecutive patients with prion disease systematically examined and investigated in the ongoing UK National Prion Monitoring Cohort study, 58 (31%) had isolated cognitive symptoms in the early stages of disease. In order to understand the features that led to correct diagnosis, we report 5 patients from this group in whom a diagnosis of young-onset or familial Alzheimer's disease was made on the basis of initial specialist assessment and investigations. They include 3 patients subsequently diagnosed with inherited prion disease, and 2 with sporadic Creutzfeldt-Jakob disease. The early distinguishing clinical and neuropsychological features may include the presence of subtle ataxia or myoclonus, and an emphasis on abnormal executive function, language output or praxis, rather than episodic memory. None of these clinical features are specific to prion disease however, and correctly identifying these cases on clinical grounds alone remains problematic. In all 5 cases the diagnosis was confirmed by PRNP genotyping or by specialist review of diffusion-weighted MR brain imaging to identify signal change and restricted diffusion in the cortex and/or basal ganglia. Prion disease can mimic the clinical presentation of Alzheimer's disease. PRNP genotyping and diffusion-weighted MR brain imaging allow early confirmation of the diagnosis. We recommend that these investigations should be considered in patients presenting with young-onset or familial dementia.