Ultra-Rapid Progressive Dementia: Characteristics of an Uncommon Neurological Disorder

ObjectiveDetermine the patient characteristics, clinical presentation, results of investigations, in patients with ultra-rapid progressive dementia (RPD). BackgroundThe term RPD refers to dementia developing within one year, or complete incapacitation within two years of symptom onset. While most RPD patients exhibit subacute deterioration, a small subset develops dementia within 7 days. The causes and contributors to this ultra-rapid form remain poorly understood. Design/MethodsOne-hundred and eighty-eight patients with RPD were prospectively enrolled in a study of RPD at Mayo Clinic (Jacksonville, Florida) and Washington University (Saint Louis, Missouri) from February 2016 to September 2023. Patients who developed persistent (≥1 month) dementia (global Clinical Dementia Rating® ≥1) within 7 days of the onset of first symptom were classified as ultra-RPD. Prospectively assessed patients were considered together with cases identified through systemic review of the extant literature to inform the patient characteristics, presenting symptoms and signs, results of common clinical tests, and causes of ultra-RPD. ResultsThree patients in our prospective study of RPD had ultra-RPD (3/188, <2%): an 80-year-old female with right fornix acute infarction; a 92-year-old female with presumed strategic stroke, and a 71-year-old male with GABAB-receptor antibody-associated encephalitis presented with sudden amnesia. An additional 55 cases (with a median age of 55.0 years at symptoms onset [range: 18-97], 36% female) were reported in 47 publications attributed to vascular (41%), toxic/metabolic (24%), autoimmune/inflammatory (21%), and iatrogenic/structural (e.g., colloid cyst removal; 9%) causes. Brain MRI changes within Papez circuit structures were common in 52/57 (91%) patients with ultra-RPD, providing a unifying localization. Twelve patients (17%) had potentially treatment-responsive causes of ultra-RPD. ConclusionsPatients with ultra-RPD are rarely encountered in clinical practice. The evaluation of patients with ultra-RPD should prioritize testing for potentially treatment-responsive vascular, toxic/metabolic, and autoimmune/inflammatory conditions that often disrupt neuroanatomical structures critical for memory formation and retrieval.