Rapidly Progressive Dementia: Key Factors That May Aid Diagnosis

Factors such as hallucinations, cortical visual loss, advanced brain atrophy, and a normal cerebrospinal fluid (CSF) white blood cell count are found to be associated with rapidly progressive dementia (RPD), according to study results presented at the 2025 American Academy of Neurology (AAN) annual meeting, held from April 5 to 9, 2025, in San Diego, California, and published in the journal Neurology.                 

Identifying cases of faster-than-expected cognitive decline with risk for RPD is important for effective patient management and research enrollment.

In a prospective study, researchers aimed to identify factors predictive of “true” RPD and distinguish them from non-RPD.

Patients with suspected RPD were enrolled at 2 tertiary centers in the US between 2016 and 2023. Dementia specialists reviewed data and confirmed diagnoses of RPD.

RPD was defined as progression to dementia within 1 year (global Clinical Dementia Rating [CDR] ≥1) or incapacitation (global CDR ≥2) within 2 years of symptom onset.

A total of 248 patients with suspected RPD were included in the analysis, of whom 187 (75.4%) met criteria for RPD.

Participants with vs without RPD were older (62.6% vs 55.0%; P <.001) and more likely to have Alzheimer disease (19.1% vs 4.6%; P =.008) or Creutzfeldt-Jakob disease (28.3% vs 9.8%; P =.003). Non-RPD cases were diagnosed as autoimmune/inflammatory conditions (42.6%) or other causes, such as psychiatric, neoplasms, toxic/metabolic conditions (34.4%).

After adjusting for age, hallucinations (odds ratio [OR], 2.86; 95% CI, 1.26-6.52) and a normal CSF white blood cell count (<5 cells/mm³; OR, 2.09; 95% CI, 1.05-4.09) were independently associated with RPD, and cortical visual loss (8.2%), advanced brain atrophy (14.7%), and periodic epileptiform discharges on electroencephalogram (71.9%) were observed in all patients with RPD.

“Early recognition of these features in patients with suspected RPD may inform clinical care and support enrollment in studies of RPD,” the researchers concluded.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.