New study defines rapidly progressive dementia

A new multicenter study led by Mayo Clinic researchers has established a practical, evidence-based definition for rapidly progressive dementia (RPD), a rare but devastating form of cognitive decline that develops over months instead of years. The findings, published in Neurology, the medical journal of the American Academy of Neurology, may help clinicians recognize and treat RPD earlier, and enable researchers to work from a shared framework when studying the condition.

While most types of dementia progress gradually, RPD advances with alarming speed, often leading to significant cognitive decline or death within one to two years. Although it accounts for around 4% of dementia cases, RPD is difficult to diagnose. Symptoms can stem from numerous causes, including autoimmune disease, infections, neurodegenerative disorders such as Alzheimer's disease and rare conditions like Creutzfeldt-Jakob disease. This makes it challenging to consistently define the disorder across different settings.

"Clinicians need a clear, standardized way to identify patients whose decline is unusually fast," says Gregg Day, M.D., a behavioral neurologist at Mayo Clinic and senior author of the study. "This helps ensure that those with potentially treatable causes are recognized quickly, wherever they are seen. Furthermore, this is a necessary step before launching multicenter studies aimed at understanding why a small subset of dementia patients progresses rapidly and how to address this through clinical trials and treatments."

The new definition proposed by Dr. Day and his colleagues uses the Clinical Dementia Rating (CDR) scale, a well-established tool for assessing dementia severity. Criteria are based on the level of functional impairment involving memory, orientation, judgment, problem-solving, community affairs, home and hobbies, and personal care. Under the new framework, a person is considered to have rapidly progressive dementia if they develop mild dementia (CDR score of 1 or higher) within one year of symptom onset, or moderate-to-severe dementia (CDR score of 2 or higher) within two years. Researchers refer to this as the "1-in-1 or 2-in-2" rule.

To test this definition, the research team applied it to two large datasets. The first, known as the RaPID cohort, included 248 patients evaluated for suspected RPD at Mayo Clinic in Florida and Washington University in St. Louis. The second used data from the National Alzheimer's Coordinating Center, representing more than 19,000 participants across 46 research centers in the United States.

In the RaPID group, about 75% of patients met the new criteria. Nearly 1 in 3 had autoimmune or inflammatory causes - many of which are potentially reversible. In the broader national dataset, about 4% met the definition for RPD, with Alzheimer's disease being the most common underlying cause. Across both groups, people who met the RPD definition declined 3 to 4 times faster than those with typical dementia, based on changes measured using the CDR scale.

The new definition proved reliable across clinical and research settings, identifying both rare and common causes of RPD. It can be applied using a patient's clinical history instead of specialized testing, making it adaptable in diverse healthcare settings, including those with limited medical resources.

"By uniformly defining rapid progression, we can better identify patients who might benefit from treatment, improve consistency in research, and ultimately enhance care for people facing one of the most challenging forms of dementia," Dr. Day says.