Gregory Day1, Philip Tipton1, Evelyn Lazar4, Nihal Satyadev5, Yuka Martens2, Steven Dunham6, Michael Geschwind7, John Morris6, Neill Graff-Radford3
1Neurology, 2Neuroscience, Mayo Clinic Florida, 3Mayo Clinic Florida, 4Neurology, JFK Medical Center, 5University of Medicine and Health Sciences, 6Washington University School of Medicine, 7UCSF
Objective:
Describe a diagnostic approach to the evaluation of patients with suspected rapidly progressive dementia (RPD) and review common causes of RPD.
Background:
Overlap in clinical features and the results of diagnostic tests confounds the etiologic diagnoses of RPD and contributes to diagnostic delays, missed treatment opportunities, and poor patient outcomes. There is a need to improve diagnostic accuracy in patients with RPD.
Design/Methods:
Patients with RPD were prospectively enrolled and evaluated in inpatient settings and outpatient subspecialty (memory) clinics at two tertiary care centers from 2016-2022. Etiologic diagnoses were independently assigned by two dementia specialists, integrating clinical features and the results of accessible diagnostic tests, and referencing established diagnostic criteria. Diagnostic disagreements were resolved via blinded review by a third specialist when required. Clinicopathologic correlation was evaluated using neuropathological and genetic data when available.
Results:
225 patients with suspected RPD were assessed, of which 154 patients (68.4%) met established criteria for RPD. The median age-at-symptom onset of RPD was 66.0 years (range: 18.3-84.7); 46.7% were female. Diagnostic inter-rater reliability (91% agreement; Cohen’s κ=0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic or genetic data). Autoimmune encephalitis was the leading cause of RPD (82/154, 53.2%), followed by Alzheimer disease and related dementias (45/154, 29.2%), including frontotemporal lobar degeneration, Lewy body disease, and vascular cognitive impairment. Creutzfeldt-Jakob disease accounted for 30/154 cases (19.4%). Other causes included neurosarcoidosis, metabolic disruptions, neoplasms, and other autoimmune/inflammatory diseases.
Conclusions:
Etiologic diagnoses can be reliably established in patients with RPD using available clinical data. Potentially treatable causes of RPD are common emphasizing the need for diagnostic approaches that improve recognition of treatment-responsive patients early in the symptomatic course.