Objective:

To improve recognition of patients with potentially treatable causes of rapidly progressive dementia (RPD).

Background:

RPD includes patients with less than two years from the onset of cognitive impairment to incapacitation due to dementia. Although RPD is often associated with invariably fatal neurodegenerative diseases such as Creutzfeldt-Jakob disease, treatable forms of RPD are increasingly recognized in clinical practice. Early recognition of treatment responsive causes of RPD is associated with earlier treatment and better outcomes.

Design/Methods:

154 patients with RPD were prospectively enrolled from February 2016 to August 2022 in studies of RPD at two tertiary care centers. Two neurologists independently determined etiologic diagnoses. Causes of RPD were further classified as treatment-responsive or non-responsive. Demographic, clinical, and paraclinical features associated with treatable causes of RPD were identified using stepwise multivariate logistic regression.

Results:

82/154 patients (53.2%) had potentially treatable causes of RPD, including autoimmune conditions (n=51, 62.2%), vasculopathies (n=17, 20.7%), psychiatric conditions (n=4, 4.8%), and nutritional deficiencies (n=4, 4.8%). Younger age at symptom onset (OR=1.22 per decade, 95%CI: 1.11-1.36), seizures at presentation (OR=6.86, 95%CI: 2.27-20.68), CSF pleocytosis (OR=6.47, 95%CI: 2.36-17.84), and MRI features suggestive of autoimmune encephalitis (OR=6.19, 95%CI: 1.21-31.79) were associated with greater odds of a treatable cause of RPD. Model performance was good (area-under-the curve = 0.81; 95%CI: 0.75-0.87; p<0.001), corresponding to >80% accuracy in detection of patients with potentially treatable causes of RPD.

Conclusions:

Treatment-responsive causes of RPD were common in our series. Younger age, early seizures, and CSF- or imaging-based evidence of inflammation should prompt consideration of treatable causes, with early initiation of treatment when indicated.