Diagnosing and Treating Rapidly Progressive Dementias

Diagnosis of rapidly progressive dementias is difficult due to broad pathology and underdeveloped diagnostic criteria for clinical settings.

Dementia may result from as many as 40 different diseases and conditions ranging from dietary deficiencies to inherited diseases, according to the Encyclopedia of Mental Disorders.1

With that, the definition of dementia has broadened over time from a focus on memory loss to a focus on impairment in one or more cognitive domains — particularly memory, language, frontal executive function, organizing, planning, and multitasking — that is severe enough to interfere with a person’s daily function.1

Typically, chronic degenerative dementias are characterized by damage or wasting away of brain tissue usually progressing over seven to 10 years. These include Alzheimer’s disease, frontal lobe dementia, and Pick’s disease. Dementias associated with progression of other diseases or conditions include Huntington’s disease, Lewy body dementia, and other parkinsonian dementias, such as corticobasal degeneration. 

Michael Geschwind, MD, PhD, associate professor of neurology at the Memory and Aging Center at the University of California, San Francisco said that although there is no defined time frame for rapidly progressing dementias (RPDs), he uses the term to describe patients that go from normal cognition to dementia within a year or less. However, he has seen some patients with Creutzfeldt-Jakob Disease (CJD) take as long as two years to develop dementia.

Although there can be overlap with some typical degenerative dementias presenting in a rapid fashion, in general, patients who may have an RPD need clinicians to consider a different set of disorders, because these conditions can be both treatable and quickly fatal in some cases, Geschwind explained.

RPDs include prion diseases such as CJD, autoimmune dementias, paraneoplastic conditions, infections that can mimic prion diseases, and fungal infections as well as some viral and toxic metabolic conditions, such as Wernicke’s encephalopathy (a condition that stems from thiamine deficiency often due to malnutrition) and even conditions stemming from complications from an overdose of Pepto-Bismol.

In a 2007 monograph on RPD published in Neurology Clinic, Geschwind’s team observed that 15% to 20% of the 825 patients referred to UCSF with rapidly progressing dementia presumed to be CJD turned out to have other non-prion conditions.2 One explanation is that the WHO criteria for CJD are designed for epidemiologic purposes and aren’t useful for making a clinical diagnosis.

“What I mean by that is the criteria are designed to ascertain the prevalence CJD within a population,” Geschwind said. “Epidemiologic surveillance for CJD looks at [cases proven at autopsy], but a lot of cases never make it to autopsy. [Researchers] want to have criteria so they can say with a high degree of certainty in a patient who didn’t have an autopsy how likely it was that they had CJD.”

As a result, those criteria are not very sensitive. In the era of treatment trial, clinicians need criteria that can be used to diagnose patients while they are still alive.

A Challenging Diagnosis

In terms of sensitivity, the diagnosis of RPDs continues to evolve. In one case report, six patients were shown to have rare rapidly progressing fatal prion dementia with prominent degeneration in the thalamus that may or may not be a completely new prionopathy. It was not found with standard tests for human prion diseases. They showed that an additional test called conformation-dependent immunoassay (CDI) might be needed when prion disease is suspected but not found with standard tests.3