Background: A clear understanding of common causes of rapidly progressive dementia (RPD) is needed to prioritize diagnostic testing, enhance diagnostic accuracy, and improve clinical management. We previously reported that rapidly progressive presentations of Alzheimer disease and related dementias (ADRD) accounted for 3.6% of cases accrued within a large neurodegenerative brain bank from 1998 to 2020. Here, we update experience over the past 5 years.

 

Methods: Patients with <4 years from the onset of cognitive impairment to death were identified within the Mayo Clinic Neurodegenerative Brain Bank across an expanded epoch: 1998-2025. Demographics, family history, dominant symptoms/signs at onset, and common comorbidities (e.g. depression, psychoses, sleep disturbance) were extracted from clinical records. Neuropathological diagnoses were assigned following standard protocols. We evaluated whether the frequency of rapid presentations of ADRD have changed over time using Chi-square tests (1998-2020 vs 2021-2025).

 

Results: 408/11738 (3.5%) cases met RPD criteria: proportions were similar before (310/8586, 3.6%) and after 2020 (98/3152. 3.1%; p=0.21). Patients with prion disease commonly presented with RPD (71%, 40/56; previously 74%; p=0.58), followed by patients with progressive supranuclear palsy/corticobasal degeneration (PSP/CBD: 6.9%, 162/2362; previously 7.5%; p=0.02) and other forms of frontotemporal lobar degeneration (FTLD: 8.5%, 50/585; previously 5.7%; p<0.0001), Lewy body disease (LBD: 4.4%, 78/1762; previously 4.1%; p=0.36), and Alzheimer disease (AD: 1.7%, 68/3807; previously 1.8%; p>0.99). Average age-at-symptom onset was 69.1±10.4 years and disease duration 2.9±1.0 years. Symptomatic duration was shortest in patients with prion disease (1.4±1.2 years). Comorbid cerebrovascular disease was reported in 23.5% of cases but was not associated with symptomatic duration. Although depression, psychosis, and sleep disturbances were common across all neuropathological groups, depression was most common in patients with FTLD (58%, p<0.015), whereas psychosis (75.6%, p<0.001) and sleep disturbances (60.3%, p<0.035) were most frequent in patients with LBD.

 

Conclusions: Rapidly progressive forms of neurodegenerative diseases accounted for 3.5% of cases in our neurodegenerative brain bank. The overall proportion of rapidly progressive cases and distribution of causes remained relatively stable over time, with exception of FTLD cases. These findings highlight the need to consider atypical presentations (i.e., rapid) of common ADRD in patients with RPD.