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Background and Objectives: The term rapid progressive dementia (RPD) may be applied to patients who develop dementia within 1 year or complete incapacitation within 2 years of the first symptom of impairment. However, in select cases, cognitive impairment may emerge abruptly, with symptoms evolving across hours or days. We sought to determine the frequency, etiologies, and factors that associated with ultra-RPD., Methods: Ultra-RPD was defined as persistent dementia (global Clinical Dementia Rating ®  ≥ 1), developing within 7 days of initial symptoms. Patients with ultra-RPD were identified via case review of patients enrolled in a prospective study of RPD at two tertiary care centers (February 2016-September 2023) followed by a systematic review of multiple English-language databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (completed January 2024)., Results: Three of 188 patients with RPD enrolled in our prospective series met the proposed definition for ultra-RPD (frequency = 1.6%). Systematic review yielded 57 additional cases from 47 publications (60 total cases). Ultra-RPD was attributed to vascular (40%), toxic/metabolic (22%), autoimmune/inflammatory (20%), and iatrogenic/structural (12%) causes. Lesions within the Papez circuit were detected in 52/59 (88%) of patients on neuroimaging. Twelve patients (20%) had potentially treatable causes of ultra-RPD., Discussion: Patients with ultra-RPD were rarely encountered in our prospective series, representing < 2% of cases of RPD, and rarely reported in the extant literature. The evaluation of patients with ultra-RPD should prioritize testing for vascular, toxic/metabolic, and autoimmune/inflammatory conditions that affect neuroanatomical structures or networks critical for memory formation and retrieval., Competing Interests: Declarations. Conflicts of interest: Yoav D Piura reports no conflicts of interest relevant to the manuscript. Nick Corriveau-Lecavalier reports no conflicts of interest relevant to the manuscript. Abd Moain Abu Dabrh reports no conflicts of interest relevant to the manuscript. Michael D Geschwind reports no conflicts of interest relevant to the manuscript. Tara Brigham reports no conflicts of interest relevant to the manuscript. Gregory S Day reports no conflicts of interest relevant to the manuscript. Ethical approval: The experimental procedure was approved by the ethics committee of Washington University School of Medicine and Mayo Clinic and complied with the ethical standards of the Declaration of Helsinki. Consent to participate: Informed consent was obtained from all individual participants or legal guardians included in the study., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Prion disease classically presents with rapidly progressive dementia, leading to death within months of diagnosis. Advances in diagnostic testing have improved recognition of patients with atypical presentations and protracted disease courses, raising key questions surrounding the relationship between patterns of neurodegeneration and survival. We assessed the contribution of fluorodeoxyglucose (FDG-PET) imaging for this purpose., Methods: FDG-PET were performed in 40 clinic patients with prion disease. FDG-PET images were projected onto latent factors generated in an external dataset to yield patient-specific eigenvalues. Eigenvalues were input into a clustering algorithm to generate data-driven clusters, which were compared by survival time., Results: Median age at FDG-PET was 65.3 years (range 23-85). Median time from FDG-PET to death was 3.7 months (range 0.3-19.0). Four data-driven clusters were generated, termed "Neocortical" (n = 7), "Transitional" (n = 12), "Temporo-parietal" (n = 13), and "Deep nuclei" (n = 6). Deep nuclei and transitional clusters had a shorter survival time than the neocortical cluster. Subsequent analyses suggested that this difference was driven by greater hypometabolism of deep nuclei relative to neocortical areas. FDG-PET-patterns were not associated with demographic (age and sex) or clinical (CSF total-tau, 14-3-3) variables., Interpretation: Greater hypometabolism within deep nuclei relative to neocortical areas associated with more rapid decline in patients with prion disease and vice versa. FDG-PET informs large-scale network physiology and may inform the relationship between spreading pathology and survival in patients with prion disease. Future studies should consider whether FDG-PET may enrich multimodal prion disease prognostication models., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)