Evaluate the performance of diagnostic criteria for autoimmune encephalitis (AE) in patients undergoing evaluation for rapidly progressive dementia (RPD) and consider the factors associated with progression to autoimmune dementia (AiD).

AE is a common cause of RPD, requiring early detection for optimal treatment. Current diagnostic criteria for AE criteria have been validated in younger cohorts with AE and common mimics. It is unknown whether these criteria can be applied to identify patients with suspected RPD due to AE.

Patients with suspected RPD were evaluated at two tertiary centers (2016-2023) and AE diagnostic criteria specified by Graus et al. 2016 prospectively documented. Two dementia specialists independently reviewed clinical data, brain imaging, electroencephalograms, and CSF/blood tests and assigned clinical diagnoses. We further assessed the patient- and disease-specific factors associated with persistent cognitive/behavioral impairment (i.e., AiD) in patients with AE.

Two-hundred-forty patients with suspected RPD were enrolled (mean age 61.3 years, 46% female), including 73 (30%) with AE. AE criteria showed good sensitivity (87%), excellent specificity (97%), and strong PPV (93%) and NPV (95%). Nine patients (12%) were missed by AE criteria (false negative), including 2 patients with LGI1-antibody-associated, and one patient each with NMDAR- and PCD-1-antibody-associated AE. Five patients without AE, met AE criteria (false positive; 5/168, 4%), including 3 patients with cerebral amyloid angiopathy with related inflammation and one patient each with Susac's syndrome and progressive multifocal leukoencephalopathy. Persistent cognitive impairment (>3 months) developed in 49/72 (68%) patients with suspected RPD due to AE. Almost all patients received immunomodulatory therapies (70/73, 96%); delayed initiation of immunomodulatory therapies was associated with AiD (mean difference: 2.3 months, 95%CI: 0.6-4.0; p-value = 0.008).