Older age and presence of prion disease were associated with shorter disease duration in patients with rapidly progressive dementia, according to findings of a study presented at the ANA 2022, the annual meeting of the American Neurological Association held in Chicago in October.¹

To determine the neuropathological causes of rapidly progressive dementia, Day et al examined 8586 brain samples in the Mayo Clinic neurodegenerative brain bank from 1998 to 2020. They also sought to examine the clinical features. For the purpose of the study, rapidly progressive dementia was defined as disease duration of less than 4 years from onset of symptoms to death. Data was obtained from medical records.

Out of the 8586 brain samples examined, 306 (3.6%) were determined to be rapidly progressive dementia with disease duration (average) of around 3 years. Nearly 40% of these were women. The median age when the symptoms first appeared was 70.8 years.

The most common cause of the dementia was prion disease (Creutzfeldt-Jakob disease) accounting for almost 75% cases. The other causes were progressive supranuclear palsy and corticobasal degeneration (7.4%), other frontotemporal lobar degeneration (5.7%) and Lewy body disease (4.1%). and Alzheimer disease caused less than 2% of cases. The shortest duration was for Prion diseases (1.6 years).

Cognitive impairment or decline was the commonest complaint among all patients, but patients with supranuclear palsy/corticobasal degeneration mainly presented with motor symptoms. Less than half (43.5%) had two or more simultaneous pathologies. However, the presence of concurrent pathologies did not affect the duration of disease.

On multivariate analysis, the disease duration was found to be shortest in patients with advanced age and Creutzfeldt-Jakob Disease, whereas pathologies like vascular disease and progressive supranuclear palsy/corticobasal degeneration were associated with longer disease duration. No such differences were observed for sex, APOEe4 carrier status, other neurodegenerative diseases and the presence of depression, hallucinations/delusions, or sleep pathology.

Unlike the slowly progressive dementia that occurs in diseases such as Alzheimers’s, rapidly progressive dementia develops within weeks to months. Although Creutzfeldt-Jakob disease is the first condition that comes to mind when managing such cases, other potentially reversible causes such as toxic encephalopathy, infectious causes, vitamin deficiencies must also be ruled out.²

Nearly 4% of dementia were rapidly progressive in nature as shown in the present study.¹ However, there was no impact of co-existing diseases or “patient-specific factors” on the duration of symptoms. Hence, the authors suggest that “rapidly progressive neurodegenerative diseases represent a distinct disease subgroup” and recommend molecular characterization of these diseases to further elucidate the underlying neuropathological causes of rapidly progressive diseases.

References

1. Day GS, et al. S115. Dissecting the causes and contributors to rapidly progressive dementia: an autopsy study. Ann Neurol. 2022;92(suppl 29): S51-S52.
2. Geschwind MD.  Rapidly progressive dementia. Continuum (Minneap Minn). 2016 Apr;22(2 Dementia):510-37.