The Clinical Dementia Rating Sum of Boxes, or CDR-SB, is a highly sensitive research tool that can be used to detect changes in a patient's condition that are meaningful, both clinically and to patients and care partners. It has been used as an endpoint in clinical trials of early Alzheimer's disease.

I'm Doctor Joy Snider, and I'm going to share the 5 top facts to know about this measure so we can better evaluate the results of these trials, regardless of whether you utilize the CDR-SB in clinical practice. Let's get started.

Fact one: The CDR-SB is valid, reliable, and sensitive in the early AD population.

AD can be divided into 5 stages. Preclinical AD, where there is evidence of AD pathology in the brain without any clinical symptoms. Mild cognitive impairment or MCI. Mild AD dementia. Moderate AD dementia and severe AD dementia. It should be noted that MCI can be associated with a number of causes such as sleep disorders, medication, depression, and other neurological disorders. Here, we are specifically referring to MCI due to AD. The earlier AD is identified and treated, the greater the opportunity for benefit. Therefore, recent clinical studies have focused on the earliest symptomatic stage of AD: MCI due to AD in the mild AD dementia stage. Because of this, there has been interest in tools that can track disease progression in early AD and clinical trials. As we said earlier, the CDR-SB has been shown to be a valid, reliable, and sensitive tool in this population, making it widely used in clinical research.

Fact 2: The CDR-SB is a measure of disease severity and is the sum of the scores across 6 domains of the CDR.

Initially developed here at Washington University School of Medicine in Saint Louis, Missouri, is a staging tool to categorize dementia severity. The Clinical Dementia Rating, or CDR, is a scale used to characterize 6 domains applicable to AD. The domains assess cognitive and functional performance. It is administered as a structured interview with both the patient and a reliable informant, such as a family member.

The CDR yields 2 scores. The global CDR, which stages disease on a scale from 0 to 3, and the CDR-SB, which is a more granular measure of disease severity and is the sum of the scores across the 6 domains.

Each domain is scored on a scale of impairment ranging from 0 to 3, with 0 being normal level of function and higher scores indicating greater impairment. The total score for the CDR-SB can range from 0 to 18. However, in early AD the typical ranges from 0.5 to 6.

This brings us to fact 3: Compared with the global CDR, the CDR-SB is more sensitive to smaller increments of change.

The use of CDR-SB scores for staging disease severity offers several advantages over the global score because the increased granularity of CDR-SB makes the assessment helpful for tracking changes across time. Furthermore, it is sensitive to smaller increments of change in a patient's cognition. Importantly, progression on an individual domain of the CDR-SB can be a meaningful change for a patient.

In early AD, natural disease progression within 18 months is 1.5 to 2 points on the CDR-SB. In fact, this is our fourth fact.

For example, let's look at the memory, orientation, and judgment and problem-solving domains.

The CDR-SB is highly sensitive and can detect changes in a patient's condition that are meaningful, both clinically and to patients and care partners.

With respect to memory, a shift of just 0.5 points on the CDR scoring table, such as progressing from 0.5 to 1, could indicate a decline from consistent, slight forgetfulness to forgetfulness that interferes with everyday activities. In my experience, patients with a score of 0.5 still remember events well, like going out to eat with friends the day before or where they went on vacation a few weeks ago.

Patients with a score of 1 are more likely to forget the pertinent details of recent events. A shift from .5 to 1 also could mean a patient who had been able to manage their own appointments may now need reminders.

With respect to the orientation domain score, at 0.5, the patient can still be driving and going places with only slight difficulty understanding time relationships. And a score of 1, driving might have to be limited to familiar areas. This could mean a change from being able to drive to visit family in a distant city to limiting driving to just their local neighborhood.

And as patients move from .5 to 1 in the judgment and problem-solving domain, they go from having mild difficulty solving problems and detecting similarities and differences, to moderate difficulty. This could meet a need for more support from a care partner to negotiate daily life. For example, a score of 0.5 indicates that patients may still manage their finances and balance their checkbook, but it might take a little longer. They may still plan a trip and book their own travel, but with a score of 1, patients will need help with these tasks.

Okay, we've made it to fact 5. The CDR-SB has been widely used in clinical trials in early AD.

This is because, as noted earlier, the CDR-SB has been shown to be a valid, reliable, and sensitive tool in the early AD population. It is also considered a clinically meaningful endpoint by the US Food and Drug Administration.

To wrap up, here are the top 5 facts to know about the use of the CDR-SB in evaluating early AD. Hopefully, this overview aids understanding of the sensitivity of the CDR-SB and its meaningfulness, both clinically as well as to patients and care partners. Please share this with your team members and colleagues to help them interpret the results of early AD clinical trials.