Over the last two decades, the neurological sciences have been home to some of the most notable innovations in all of medicine, boasting new treatment classes and therapeutic guidelines in disease states such as stroke, multiple sclerosis, and headache. Despite these gains, however, much work remains in the effort to better understand and address the massive scope and burden of neurological diseases. Nowhere is this more apparent than in the treatment spectrum for Alzheimer’s disease (AD), which has been defined, of late, by a 14-year drought in new treatments.
Many symptomatic and disease modifying agents explored during that time have been unsuccessful in showing statistically significant clinical benefits, but according to Douglas Scharre, MD, Professor of Clinical Neurology and Psychiatry at The Ohio State University’s (OSU) Center for Memory and Cognitive Disorders, new research regarding the pathophysiology of the disease itself and early detection techniques are potentially laying the groundwork for a brighter future in care. Specifically, the realm of cognitive screening is of particular interest to Dr. Scharre, who developed the cognitive screening test called Self-Administered Gerocognitive Exam (SAGE), which has since been developed into a digital version called BrainTest. Ahead, Dr. Scharre shares insights on the recent advances in cognitive screening and discusses the impact new screening tools could have on the broader management of cognitive disorders and dementia conditions including AD.
How would you describe the recent trajectory of research regarding Alzheimer’s disease, dementia, and more generally cognitive decline?
One consistent theme in new research in the AD arena is the importance of early detection, according to Dr. Scharre. “Some of the key findings from research studies suggest that early detection is better for management,” he says. “Whether a patient is being treated with disease modifying agents or older, symptomatic therapies, one thing we have learned is that all of these agents seem to work better when they are started earlier.” Fortunately, Dr. Scharre observes, several threads of inquiry have emerged in recent years pertaining to the development of biomarkers for early and accurate detection of AD, including amyloid PET, CSF biomarkers, and more recently tau PET imaging. In addition to these new developments, Dr. Scharre believes that neurologists should more seriously consider utilizing what he calls cognitive biomarkers. “Evidence from the Alzheimer’s Disease Neuroimaging Initiative and other trials suggest that cognitive tests can be used as early biomarkers for the detection of mild cognitive impairment (MCI).” Moreover, “the research suggests that particularly executive and memory impairment are some of the earliest changes noted in MCI due to AD. We can potentially use these cognitive profiles to identify individuals at very early stages of their disorder and follow for changes over time.”
Cognitive Screening Resources
BrainTest is not yet available, as the company awaits publication of validation data. Patients and physicians can learn more about it at the company’s website. A downloadable version of the pen and paper SAGE test is available on the Ohio State University Center for Cognitive and Memory Disorders site, along with other resources for patients on early signs of cognitive and brain dysfunction.
“Unfortunately, patients often come to the doctor too late in the process. This may be due to impaired insight, embarrassment over ‘losing it,’ or maybe they think their cognitive loss is due to normal aging,” says Dr. Scharre. On average, he points out that it takes roughly three to four years after patients notice changes in cognitive abilities before they first visit their PCP. “Typically, by the time neurologists see these patients, they’re already in the mild to moderate stages of dementia.” This underscores the need for identifying cognitive impairment at the MCI stage, Dr. Scharre suggests, especially given that therapies are more effective when started early. This notion holds true particularly in light of the recent efficacy research on experimental disease modifying therapies, he further notes.
Can you talk about the importance and need for cognitive screening tools?
“There are definite advantages to having cognitive assessments performed, particularly if you’re at higher risk—such as patients who are at an increased age, have a family history, or are worried about cognitive decline,” says Dr. Scharre. Any patients who have these risk factors should receive baseline cognitive testing and be clinically evaluated, he notes. “Each of us has different talents—some are good with words, or math, or have artistic abilities. So getting a baseline cognitive assessment is critical. Repeat assessments represent the only way to identify if someone is declining from their baseline over time.” Such evaluations may help physicians to identify MCI at an earlier stage.
Dr. Scharre points out that many cognitive assessment tools are currently available. “There are excellent brief evaluations, pen-and-paper tests, and computer exams all the way up to and including neuropsychological tests that may take hours to complete,” he says. However, the crowded field of cognitive screening tools can make it difficult for physicians to determine which are useful.
For initial cognitive screening, Dr. Scharre believes that tools that are easy to administrate and score and that can be validated clinically and scientifically are essential to identify cognitive loss, “so that, if appropriate, patients can begin the conversation of their symptoms with family members and physicians to help identify next steps.” To better meet this need, Dr. Scharre headed up a team of collaborators at The Ohio State to develop a test. “As a cognitive neurologist specializing in AD, I was mostly frustrated seeing patients referred to me many years after their cognitive symptoms started,” he recounts. “That got me interested and engaged in finding a better test.”
In the development of SAGE, Dr. Scharre felt that one of the most essential elements to its success was self-administration. “With the great help of OSU and our team of researchers, I developed and designed SAGE as a practical tool to help people identify impairment at the MCI stage,” he observes. “We needed a test that individuals could take on their own without the use of a medical assistant or nurse to administer it; patients can take it in the doctor’s office, in their own home or virtually anywhere in about 15 minutes. Then, it can be taken to a physician for scoring, interpretation and to decide about further evaluation that may be needed based on that.”
Another critical aspect of SAGE is its validation. “We did a validation study on the paper SAGE test, and in that study we correctly identified 80 percent of people who had MCI and memory issues,” he said. We based it on the gold standard of a clinical evaluation including an extensive battery of neuropsychological testing.” Dr. Scharre notes further that SAGE, in addition to 80 percent sensitivity, also yielded a specificity of 95 percent, i.e., correctly identifying patients who were determined not to have cognitive impairment.
There are four equivalent versions of SAGE, all with excellent test-retest reliability, according to Dr. Scharre. SAGE was further evaluated in the community regarding its effectiveness as a cognitive assessment tool. “We assessed more than 1,000 patients over 50 years old, from multiple community events and we concluded that SAGE was internally consistent and well balanced in scoring for language, visuospatial, executive, memory and reasoning/computation cognitive domains, all of which were represented fairly equally in the total score.”
Regarding its role in care, Dr. Scharre points out that SAGE and now BrainTest, the digital adaptation of SAGE, are not diagnostic tests. They are intended to reassure those whose score is normal, and motivate people with less positive scores to visit their doctor in early stages of potential cognitive decline. “Detecting signs earlier would allow people to seek treatment options and perhaps prompt increased supervision to help keep them safe,” he says.
Can you explain how and why the SAGE test is being adapted into a digital version?
“We live in a digital age, so we needed to find a practical digital solution to cognitive testing.” According to Dr. Scharre, the company BrainTest Inc. (braintest.com) was interested in making a digital form of SAGE for use on an iPad or Android tablet, with the specific goal of ensuring that it was scientifically validated. “We took the exact questions and converted them to a digital platform without changing the substance of any question,” he says. “We then compared BrainTest to SAGE and other classical neuropsychological tests,” says Dr. Scharre. A validation clinical trial was completed and presented in July 2016 at the Alzheimer’s Association International Conference in Toronto. “Results presented showed that BrainTest performed very similarly to the validated paper test, with no evidence of scale bias.”
In addition to enhanced functionality, BrainTest offers the option of timing the assessment, which is not possible with the pen and paper version. Additionally, Dr. Scharre says, BrainTest is remotely scored in a core-lab model, which removes the need for physicians to learn how to score the test. “Physicians are provided the item scores and interpretations, can explain the results to patients, and can also track results over time to help better evaluate cognitive health,” he says.
“Physicians appreciate practical solutions that save them time, and so these types of tests could have a significant impact on their multi-step approach to reaching a diagnosis and developing a care plan,” says Dr. Scharre. “For example, physicians are encouraged to evaluate for cognitive issues during their patient’s Medicare Annual Wellness Visit—any tools to help them achieve these goals are often very appreciated.” A self-administered and clinically validated test would not only offer flexibility in an office setting by eliminating the need for a staff person to administer the test, but would also provide an objective cognitive assessment that can determine if further evaluation is needed. Knowing a patient’s cognitive status will likely, eventually, reduce costs for patients and the broader health system, he suggests. “Normal results may also help avoid unnecessary costly diagnostic evaluations that ultimately also saves healthcare dollars.”
For patients, the self-administered aspect of the test may also prove particularly beneficial. “Many patients don’t like to go to the doctor and be tested for their cognitive abilities by health care workers,” Dr. Scharre observes. The self-administered feature takes away many common stressors for patients who get nervous answering test questions in front of people. Less stressful visits better facilitate conversations between physicians and patients. “If a patient does poorly, perhaps a discussion about the possibility of more supervision would be warranted. And for patients who do well but may be worried about cognitive decline, physicians can provide some reduction of angst or anxiety and help with their peace of mind by having them retake the self-administered test over time. This allows close monitoring of their concern.”
Ultimately, BrainTest combines the advantages of SAGE with an accessible digital format and offers potential widespread availability, according to Dr. Scharre. He also points out that BrainTest may enable physicians to reach patients who reside in areas where it is difficult to visit their health care provider and are far from specialized cognitive evaluation centers. “The hope is that these tests could be used to provide cognitive assessments in rural areas where access to a physician can be more limited, as well as in underserved populations. Giving individuals more control of their situation and encouraging further conversations with a physician about their cognitive and memory concerns is a goal.”
What are your take-home thoughts on the future of cognitive screening, particularly as it relates to the patient-physician relationship?
“Based on current trials we are learning that we can think of cognitive assessments as important biomarkers,” says Dr. Scharre. For patients who notice subtle cognitive changes and wish to explore that on their own before speaking with a physician, self-administered cognitive tests could provide an important resource and a stepping-stone for better communication between physicians and patients.” Additionally, he observes, the availability of these tests in a digital platform with widespread availability could have innumerable benefits beyond the physician-patient relationship. “The wide adoption of this test might help with referrals to clinical trials for appropriate individuals with MCI. This could lead to research trials being completed faster and better treatment options in the future for dementia patients,” he notes. For these reasons, digital self-administered cognitive screening tools will likely become a major factor in overcoming the many obstacles we find in identifying early cognitive changes,” Dr. Scharre suggests.
Douglas Scharre, MD is a Professor of Clinical Neurology and Psychiatry and Director of the Division of Cognitive Neurology at The Ohio State University.