Novel Test Can Detect Onset of Neurodegenerative Disease Before Symptoms Present

April 23, 2021
Matthew Gavidia
Matthew Gavidia

Matthew is an associate editor of The American Journal of Managed Care® (AJMC®). He has been working on AJMC® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

A recently published study found that the DCTclock, a test for cognitive assessment, was associated with greater detection of biomarkers related with cognitive decline in patients who had yet to show any symptoms when compared with traditional testing methods.

A novel neurocognitive and neuromotor assessment test called the DCTclock, a digital version of the classic Clock Drawing Test, was effective in detecting the beginnings of Alzheimer disease (AD) pathology among cognitively normal (CN) patients who had yet to show symptoms of dementia, according to study findings published in Neurology.

For neurodegenerative diseases, the significance of biomarkers and genetics have grown in recent years as researchers seek to better understand the pathogenesis of conditions such as AD and Parkinson disease (PD) and develop targeted therapies. Notably, amyloid beta plaques, a protein prevalent in AD that also presents in PD, can appear in the brain as early as 15 to 20 years before clinical symptoms begin.

To assess these symptoms, the gold standard of cognitive testing includes the Clock Drawing Test, conducted via pen and paper that can be time consuming and lack the sensitivity to detect neurocognitive disease early in its course. Moreover, tests that can assess neurodegenerative biomarkers, such as positron emission tomography (PET) brain imaging scans, are expensive and can be inaccessible for some patients.

As a lower cost cognitive test that takes approximately 2 minutes to administer, the Linus Health DCTclock has been registered as a Class II medical device by the FDA. In the study, the DCTclock was compared to that of standard neuropsychological assessments, including the Preclinical Alzheimer Cognitive Composite (PACC) and amyloid/tau PET imaging, in detecting biomarkers of amyloid and tau pathology in CN older adults.

Among the 300 participants who were recruited, 264 were CN—143 of these patients had amyloid and tau PET imaging (Clinical Dementia Rating [CDR], 0; Mini-Mental State Examination [MMSE] mean [SD], 28.9 [1.2])—and 36 had a diagnosis of mild cognitive impairment or early AD-related dementia (CDR, 0.5; MMSE, 25.2 [3.9]).

In their findings, the DCTclock was able to effectively discriminate between diagnostic groups, and among CN participants with biomarkers, proved better at detecting and discriminating for amyloid and tau burden than the PACC.

In an email exchange with The American Journal of Managed Care® (AJMC®), the chief executive officer of Linus Health, David Bates, PhD, spoke further on how the low-cost, efficient test can be effective in examining scalable symptoms of progressive neurological disorders such as PD and AD, as well as why detection of underlying symptoms of cognitive decline could prove vital amid increasing associations of neurological illness among survivors of COVID-19.

AJMC®: Can you speak on how cognition is typically assessed, and the cost and outcome implications of current standards of care?

Bates: Cognitive screening is recommended for elderly patients in the primary care setting. These screens include standard paper-based assessments that are meant to be completed by primary care physicians, but they are time consuming to complete in the setting of a busy practice, don’t have high sensitivity or specificity, and can be subject to administrator bias.

Following the initial assessment, patients who are suspected to have some cognitive impairment are usually referred to specialists, but an appointment with an expert neuropsychologist can take months to secure and it typically involves several hours of testing. Following lengthy neuropsychological evaluations, confirmatory follow-up testing is needed to get to the diagnosis of the underlying disease.

Although confirmatory tests such as a PET scans, cerebrospinal fluid taps, or MRI tests are objective and sensitive, they are expensive, invasive, and time-consuming. The PET scan costs up to $6000 per scan, and it requires a radiotracer to be injected into the patient. It’s important to note that these tests do not assess cognitive function, rather they reveal potential underlying pathology.

Early detection is the key to optimizing outcomes. Patients with cognitive impairment need to be identified at the earliest onset of symptoms, or even before they’re detected and begin to impact the patient’s daily life, in order to develop a care plan that can stave off disease progression, delay dementia, and minimize decline for AD, dementia, PD, or other impairments. However, most cognitive assessments are not sensitive enough to detect pre-symptomatic impairment or they require considerable time with a specialist, which is not scalable.

AJMC®: For several cognitive conditions there are suggested factors that play a significant role in its pathogenesis, such as beta amyloid for AD and alpha synuclein for PD. Can you explain the mechanisms of this device in assessing cognitive health for these diseases, as well as other cognitive conditions that may lead to dementia but do not have concrete biomarkers as of yet?

Bates: The Linus Health DCTclock test assesses neurocognitive and neuromotor function regardless of the underlying pathology. When individuals take the test, they’re prompted to draw an analog clock. On the tablet, we collect about 100 clinically significant metrics from the whole process, including the drawing, location, size, relationship, etc. There are also other tests that we use which collect data such as voice and speech patterns, visuospatial memory, dual-tasking ability and fine motor control, as well as movement, balance, and pulmonary capacity, and more.

For AD, the recent study found that the DCTclock test in the Linus Health platform was able to indicate the beginnings of AD pathology in CN individuals, those with no outward symptoms of dementia. After the individuals took the DCTclock test, the results were compared against PET scans, which correlated with the evidence of amyloid plaques in asymptomatic individuals.

The test takes under 3 minutes to perform, making it easier and more accessible for providers to administer to patients in a variety of settings. Linus Health also has other tests that can be called up and rapidly administered to further assess cognition, behavioral health, identify tremors associated with PD or symptoms of ALS.

AJMC®: Psychiatric and neurological illnesses have been reported in survivors of COVID-19 at rates twice those seen among those with the flu and other respiratory conditions. How can this tool be leveraged in the general population to assess for risk of dementia and other cognitive disorders? And what further measures should be taken to address the negative impact of COVID-19 on brain health?

Bates: Many studies have been published detailing the correlation between contracting COVID-19 and experiencing impaired cognition long after recovery; people suffering from it sometimes refer to it as a brain fog. The cognitive effects of COVID-19 have elevated the awareness of the need for better access to brain health care.

The increased risk of cognitive issues associated with contracting COVID-19 sheds light on the issue that everyone should have regular cognitive health screenings, not just the elderly or those who have contracted an inflammatory illness. However, time and cost implications of traditional tests limit the access to cognitive assessment for patients.

Linus Health and tests like the DCTclock are designed for rapid, sensitive screening, and longitudinal monitoring of brain function, which enables greater access to brain health care for everyone and early detection of cognitive issues.

Early detection is key and being able to detect functional impairment that may arise from the presence of amyloid plaque before showing clinical symptoms of impairment opens the opportunity for better research, characterization, and treatments.