Rapidly progressive dementias — aetiologies, diagnosis and management

Rapidly progressive dementias (RPDs) are a group of heterogeneous disorders that include immune-mediated, infectious and metabolic encephalopathies, as well as prion diseases and atypically rapid presentations of more common neurodegenerative diseases. Some of these conditions are treatable, and some must be diagnosed promptly because of their potential infectivity. Prion disease is considered to be the prototypical RPD, but over the past two decades, epidemiological reports and the identification of various encephalitis-mediating antibodies have led to a growing recognition of other encephalopathies as potential causes of rapid cognitive decline. Knowledge of RPD aetiologies, syndromes and diagnostic work-up protocols will help clinicians to establish an early, accurate diagnosis, thereby reducing morbidity and mortality, especially in immune-mediated and other potentially reversible dementias. In this Review, we define the syndrome of RPD and shed light on its different aetiologies and on secondary factors that might contribute to rapid cognitive decline. We describe an extended diagnostic procedure in the context of important differential diagnoses, discuss the utility of biomarkers and summarize potential treatment options. In addition, we discuss treatment options such as high-dose steroid therapy in the context of therapy and diagnosis in clinically ambiguous cases. The term ‘rapidly progressive dementia’ (RPD) describes a cognitive disorder with fast progression, leading to dementia within a relatively short time. This Review discusses the wide range of RPD aetiologies, as well as the diagnostic approach and treatment options. Key points Definitions of rapidly progressive dementia (RPD) vary according to the aetiological background and relate to the speed of cognitive decline, time from first symptom to dementia syndrome and/or overall survival. RPD can occur in rapidly progressive neurodegenerative diseases, such as prion diseases, or in primarily slowly progressive diseases as a consequence of intrinsic factors or concomitant pathologies. Besides neurodegenerative diseases, inflammatory (immune-mediated and infectious), vascular, metabolic and neoplastic CNS diseases are important and frequent causes of RPD. To identify treatable causes of RPD, the technical diagnostic work-up must include MRI and analyses of blood and cerebrospinal fluid, and further diagnostics might be indicated in unclear cases. Therapeutic options for many non-neurodegenerati