A 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 rather than years. The findings, published in Neurology, the medical journal of the American Academy of Neurology, can help healthcare professionals recognize and treat RPD earlier, and also allow researchers to work from a common framework when studying this condition. While most types of dementia progress gradually, RPD advances at an alarming rate, often leading to significant cognitive decline or death within one to two years. In the largest national dataset, about 4% met the definition of RPD, with Alzheimer's disease being the most common underlying cause. Additionally, this is a necessary step before launching multicenter studies aimed at understanding why a small subgroup 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 widely validated tool for assessing the severity of dementia. This definition can be applied based on a patient's clinical history without the need for specialized tests, making it adaptable to different care settings, including those with limited medical resources. 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 over 19,000 participants from 46 research centers across the United States. In both groups, individuals who met the RPD definition experienced decline 3 to 4 times faster than those with typical dementia, as measured by changes on the CDR scale. The new definition proved reliable in both clinical and research settings, identifying both rare and common causes of RPD. Although it accounts for about 4% of dementia cases, RPD is difficult to diagnose. This makes it challenging to define the disorder consistently across different clinical settings. “Clinicians need a clear, standardized way to identify patients whose decline is unusually rapid,” says Gregg Day, M.D., a behavioral neurologist at Mayo Clinic and the study's lead author. “By defining rapid progression uniformly, we can better identify patients who might benefit from treatment, improve research consistency, and ultimately optimize care for people facing one of the most complex forms of dementia,” states Dr. Day. Researchers refer to this criterion as the “1-in-1 or 2-in-2” rule. According to this new framework, a person is considered to have rapidly progressive dementia if they develop mild dementia (a CDR score of 1 or higher) within one year of symptom onset, or moderate-to-severe dementia (a CDR score of 2 or higher) within two years. Symptoms can have multiple causes, including autoimmune diseases, infections, neurodegenerative disorders like Alzheimer's disease, and rare conditions like Creutzfeldt-Jakob disease. In the RaPID group, approximately 75% of patients met the new criteria. Nearly 1 in 3 had autoimmune or inflammatory causes — many of them potentially reversible. “This helps ensure that people with potentially treatable causes are recognized quickly, no matter where they are cared for,” the researchers add. The criteria are based on the level of functional decline affecting memory, orientation, judgment, problem-solving, community affairs, home and hobbies, and self-care.
