Rapidly Progressive Dementia in the Outpatient Clinic: More Than Prions

Abstract

Background: Published approaches to the evaluation and management of patients with rapidly progressive dementia (RPD) have been largely informed by experience at academic hospitals and national centers specializing in the diagnosis of Creutzfeldt-Jakob disease. Whether these approaches can be applied to patients assessed within lower-acuity outpatient settings is unknown.

Methods: A total of 96 patients with suspected RPD were assessed within the Washington University School of Medicine (Saint Louis, MO) outpatient memory clinic from February 2006 to February 2016. Consensus etiologic diagnoses were established following independent review of clinical data by 2 dementia specialists.

Results: In total, 67/90 (70%) patients manifested with faster-than-expected cognitive decline leading to dementia within 2 years of symptom onset. Female sex (42/67, 63%), median patient age (68.3 y; range, 45.4 to 89.6), and years of education (12 y; range, 6 to 14) were consistent with clinic demographics. Atypical presentations of common neurodegenerative dementing illnesses accounted for 90% (60/67) of RPD cases. Older age predicted a higher odds of amnestic Alzheimer disease dementia (OR, 2.1 per decade; 95% CI, 1.1-3.8; P=0.02). Parkinsonism (OR, 6.9; 95% CI, 1.6-30.5; P=0.01) or cortical visual dysfunction (OR, 10.8; 95% CI, 1.7-69.4; P=0.01) predicted higher odds of another neurodegenerative cause of RPD, including sporadic Creutzfeldt-Jakob disease.

Conclusions and relevance: The clinical environment influences the prevalence of RPD causes. The clinical evaluation should be adapted to promote detection of common causes of RPD, specific to the practice setting.

Figure 1:

Rates of change in CDR-SB at diagnosis. The annualized rate of change in the CDR-SB is shown at the time of RPD designation, stratified by clinical diagnosis. Annualized rates of change were greatest in patients with RPD due to prion disease or “other” (non-neurodegenerative) causes. Differences were evaluated using an analysis of covariance (ANCOVA), controlling for age, and adjusting for multiple comparisons. The dashed horizontal line depicts mean annualized rates of change reported in patients with typical amnestic AD dementia (±95% CI).

Figure 2:

Kaplan-Meier ‘survival’ curves. A. Depicting time from diagnosis to death or severe dementia (CDR 3), stratified by clinical diagnosis. B. Depicting time from diagnosis to death or severe dementia (CDR 3), stratified by the presence or absence of secondary diagnoses. Events were defined as death or the development of severe dementia (CDR 3). Participants lost to follow-up were censored at the time of their last assessment. No differences were noted in time to outcome across groups (log-rank statistics, p>0.05).

Figure 3:

Diagnostic testing in RPD patients. The prevalence of diagnostic testing performed in RPD patients is depicted together with the frequency of abnormal test results. CSF biomarker profiles deemed consistent with AD or CJD were labelled as “abnormal”. Similarly, the detection of disease-associated autoantibodies in serum or CSF were labelled “abnormal”.