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March 7, 2023/Geriatrics

New Cognitive Battery Reliably Screens for MCI, Early AD in Primary Care Setting

Self-administered tool can be completed in 10 minutes in waiting room


The Cleveland Clinic Cognitive Battery (C3B) — consisting of self-administered digital modules of visual memory and processing speed tests — effectively discriminates between healthy aging and cognitive dysfunction, reports a team of Cleveland Clinic investigators. The battery, which can be completed independently by patients in a primary care clinic and is automatically scored, offers a new rapid screening tool for mild cognitive impairment (MCI) and early Alzheimer’s disease (AD).


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“The C3B is a low-cost alternative to clinician-administered cognitive testing that can be readily integrated into primary care clinical practice,” says Stephen Rao, PhD, lead author of a series of studies of the C3B from validation to initial implementation, as described in the Journal of Alzheimer’s Disease. “As a screening test for older adults, it can facilitate detection of cognitive dysfunction earlier in its course so that preventive and therapeutic interventions can be started when they are more likely to be effective.”

Dr. Rao is Director of the Schey Center for Cognitive Neuroimaging at Cleveland Clinic and staff in the Lou Ruvo Center for Brain Health, Cleveland.

Timely and efficient cognitive testing needed

Experts increasingly recognize that the brain changes associated with AD typically start many years before the disease is diagnosed. Interventions to reduce risk factors — including lifestyle changes and specific therapies as they become available — are likelier to prevent or delay onset of dementia if implemented early. But most patients do not seek care until symptoms of cognitive impairment are noticeable, when interventions are less likely to help. Current early cognitive tests are impractical as general screening tools, as they are administered by a professional and take significant time to complete.

In 2014, the National Institute on Aging recommended integrating cognitive screening tools into primary care clinical practice with minimal disruption to workflow in order to facilitate detection of MCI and early AD in asymptomatic older adults. In response, the Cleveland Clinic team developed the C3B, a self-administered instrument comprising a visual memory test (for episodic memory) and a processing speed test (for information processing and attention maintenance). The battery is taken on an iPad and can be completed and scored within 10 minutes.

Five studies: designs and findings

As detailed in the Journal of Alzheimer’s Disease report, the team conducted a series of investigations designed to validate the C3B and assess its reliability in real-world settings:

  • Study 1: Generating regression-based norms. TheC3B was tested in 428 cognitively intact, healthy adults aged 18 to 89 years at four testing sites. Performance was found to be influenced primarily by age, education and race, and adjusted z-scores were developed to allow more accurate clinical interpretation.
  • Study 2: Evaluating reliability and practice effects. Testing was conducted twice — with two weeks in between — in 30 healthy older volunteers (mean age, 73.5 years). Both C3B modules were found to have acceptable test-retest reliability and negligible practice effects.
  • Study 3: Discriminating MCI from healthy aging. C3B results from the study 2 cohort were compared with those of 30 demographically matched patients with an established diagnosis of MCI. The C3B was found to discriminate MCI from healthy aging as effectively as standardized cognitive tests used in neuropsychological clinical practice and better than the Mini-Cog, a commonly used primary care screening test.
  • Study 4: Assessing test-taking in a distracting setting. The C3B was taken by 29 healthy older adults (mean age, 72 years) in a private room and in a clinical waiting room while wearing noise-cancelling headphones. The tests were administered one hour apart with a counterbalanced design. No significant individual performance differences were observed.
  • Study 5: Determining completion rates and patient satisfaction. In this demonstration project, the C3B was administered to 470 consecutive patients (mean age, 73.8 years; range, 65-99) who came to Cleveland Clinic for a Medicare annual wellness checkup. The completion rate was high (> 92%), as were measures of satisfaction (ratings of clarity of instructions, test difficulty, feeling that testing is important).


“Our results indicate that the C3B can be an excellent general screening tool for early cognitive dysfunction in patients 65 and older,” Dr. Rao observes. “Importantly, it can be incorporated inexpensively into the regular workflow in a primary care clinic.”

Clinical implementation starts as research refinements continue

Dr. Rao emphasizes that the C3B does not depend on reports about cognitive function from patients or family members, which often are unreliable indicators of MCI or early AD. Instead, the C3B directly tests cognitive function in a manner that demonstrates high discrimination between healthy aging and cognitive dysfunction.

His team is currently preparing for a large multisite study to better define test result thresholds for cognitive dysfunction and to expand diversity of the test population. Patients — both those who score well and those who score poorly on the C3B — will be randomly selected to undergo MRI scanning, laboratory tests, extensive cognitive testing and a neurological examination to determine whether they are cognitively healthy or have MCI/AD or some other form of dementia.

Dr. Rao notes that the C3B will soon be incorporated into the primary care waiting room at Cleveland Clinic Hillcrest Hospital, which has advanced imaging capabilities for the validation studies. “Because our current evidence is strong, we will start using the C3B for clinical screening purposes and not only for research,” he adds. “Patients with test results suggesting cognitive dysfunction deserve to be offered further workup promptly.”

Disclosure: Dr. Rao reports that he has co-authored intellectual property around the C3B software for which he has received royalties from Cleveland Clinic.


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