Identification and diagnosis of ultra-rapid progressive dementia: evidence from a prospective cohort study and systematic literature review.

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.