FDA Has Cleared New Cognitive Screening Tests

The Food and Drug Administration recently cleared, meaning it deemed safe, two tests that may help doctors screen for cognitive decline. One is the so-called Cognision system from Neuronetrix, a company based in Louisville, Kentucky. It is an electroencephalography (EEG) device that allows non-specialists to measure electrical activity in the brain with a portable, hand-held recorder. It can be used to estimate cognitive performance, said company CEO K.C. Fadem. The other is a cognitive assessment battery that can be administered on a mobile device, such as a smartphone or tablet. Called the Defense Automated Neurobehavioral Assessment (DANA) and developed by AnthroTronix in Silver Spring, Maryland, this set of tests measures items like reaction time, spatial discrimination, and memory. It was originally developed to detect cognitive impairment in soldiers on the battlefield, as well as likely causes, be they concussion, combat distress, or exhaustion. The company is now trying to expand its potential uses to clinical settings, said Corinna Lathan, its CEO.

Signal in the Brain Waves
The Cognision system measures event-related potentials. ERPs are voltage patterns measured at the scalp, which are generated from the coordinated firing of populations of neurons in the brain. Characteristic ERPs occur at set times after a stimulus and are thought to reflect specific cognitive processes, such as the brain’s initial evaluation of a sensory input and its subsequent processing of that information (see Nov 2011 conference story). Though scientists have been measuring ERPs for decades, they have only recently become attractive as biomarkers for Alzheimer’s disease (AD) (see Nov 2012 conference story). Major barriers have been the expertise and special equipment needed to measure ERPs.

One Cap Fits All?

The Cognision system measures EEGs with a portable, hand-held unit. [Image courtesy of Neuronetrix.]

Neuronetrix sees a marketing opportunity in these hurdles. The Cognision system simplifies EEG measurements with electrodes built into a cap, and a wireless, battery-operated system that captures and analyzes data. Set-up takes 10 minutes, and the tasks themselves 10 to 30 minutes. The system delivers a series of sounds through earphones, and the electrodes measure ERPs as the person either listens or responds to certain tones by pressing a button. The ERPs then tell clinicians if a person performs within the normal range for their age. Over time, the ERP may flag whether cognitive impairment is progressing, Fadem told Alzforum. The device received 510k clearance, meaning that the FDA established that it was substantially equivalent to an already legally marketed device, and just as safe and effective at measuring ERPs.

In a typical ERP signal, the highest peak is strong and comes soon after the stimulus. As people age, and more so as AD progresses, that peak weakens and gradually gets delayed. “That electrical activity depends on contact between nerve cells and propagation of the electrical impulse,” said Gregory Jicha, University of Kentucky, Lexington. “The signals become abnormal because of underlying synaptic dysfunction, an early change in AD that may precede development of plaques and tangles,” Jicha explained. He was a site leader in a previous trial reporting that ERPs measured with Cognision differentiated people with Alzheimer’s from healthy controls.

Whether the test can detect preclinical trouble is still unknown. Two studies reported that ERP changes occur 10 years before the onset of familial Alzheimer’s disease (see Quiroz et al., 2011; Golob et al., 2009). Such studies suggest ERPs may be a good preclinical biomarker, said Karim Bennys, Montpellier University Hospital, France. ERPs are cheaper and less invasive than imaging and spinal fluid biomarkers, he said. His previous studies imply that ERPs predict progression from mild cognitive impairment (MCI) to AD (see Bennys et al., 2011). 

Neuronetrix will market Cognision to Alzheimer’s specialty centers and clinics that evaluate patients for cognitive problems. Eventually, they will market to primary care practitioners as well. Fadem suggested that ERPs could help assess potential Alzheimer’s treatments in clinical trials. Two clinical trials are using Cognision as a secondary outcome measure: the HAND study of HIV-associated dementia, based at East Tennessee State University, Johnson City, and a Phase 2a trial assessing the sigma-1 agonist Anavex 2-73 in patients with AD. The system was also used to measure ERPs for a study on the nutritional supplement Alpha BRAIN (see company press release). 

Some scientists commented privately to Alzforum that they are unsure whether ERPs are ready for prime time as an efficacy biomarker for Alzheimer’s drug candidates, since little evidence exists yet that these signals change over time.

A Mobile-Friendly Test Battery
DANA comprises a library of cognitive and psychological tests. It is meant to be modular, in that the user can choose what to assess. DANA comes in three main versions ranging from a rapid, five-minute screen with simple measures of reaction time (see image below) to a 45-minute evaluation that adds tests of learning and memory and questionnaires about sleep and stress (see Lathan et al., 2013).

Reaction time reflects attention and processing speed, attributes that underlie higher cognitive functions, Lathan said. DANA is not specific for Alzheimer’s, or even memory. However, it does pick up subtle cognitive decline that could result from concussion, post-traumatic stress disorder, depression, or dementia, Lathan said. Patients could take the rapid version at annual health checks to give a quick measure of brain health, she suggested. If DANA indicates deterioration from the year before, the doctors could refer patients for further testing.

The Patient Affordable Care Act of 2010 requires that Medicare pay for an annual wellness visit—including a test for cognitive impairment. Because the Centers for Medicare and Medicaid Services has not identified specific tests for reimbursement, primary care physicians are left to choose. Guidelines formulated by an expert panel convened by the Alzheimer’s Association recommend several quick tests, including the AD8, the General Practitioner Assessment of Cognition, and the Memory Impairment Screen, but they did not evaluate DANA (see Cordell et al, 2013).

Test in a Tablet.

DANA’s battery of tests is administered on a mobile device. [Image courtesy of AnthroTronix.]

AnthroTronix is exploring if DANA could be applied more specifically to dementia patients. The Burke Rehabilitation Hospital in White Plains, New York, will evaluate in a pilot study whether a 30-minute version, taken once a week at home, detects cognitive impairment and change in AD patients over three months. This version includes tests of visuospatial processing, learning, memory, sustained attention, and response control.

Michael Weiner, University of California, San Francisco, cautioned that reaction time is a simple measure of brain function and said he is unsure what value it will have in clinical trials. DANA is currently not validated for use in MCI or AD, and the sensitivity and specificity to detect those conditions are unknown, he said. Predictive and longitudinal validity of DANA has been reported for testing people who experienced hypoxia due to altitude changes and Marines who had suffered concussion (Roach et al., 2014; Spira et al., 2014).—Gwyneth Dickey Zakaib 

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References

News Citations

  1. EEG: Coming in From the Margins of Alzheimer’s Research?
  2. CTAD: EEG Gains Luster as More Trials Incorporate Biomarkers

Therapeutics Citations

  1. Blarcamesine

Paper Citations

  1. Quiroz YT, Ally BA, Celone K, McKeever J, Ruiz-Rizzo AL, Lopera F, Stern CE, Budson AE. Event-related potential markers of brain changes in preclinical familial Alzheimer disease. Neurology. 2011 Aug 2;77(5):469-75. PubMed.
  2. Golob EJ, Ringman JM, Irimajiri R, Bright S, Schaffer B, Medina LD, Starr A. Cortical event-related potentials in preclinical familial Alzheimer disease. Neurology. 2009 Nov 17;73(20):1649-55. PubMed.
  3. Bennys K, Rondouin G, Benattar E, Gabelle A, Touchon J. Can event-related potential predict the progression of mild cognitive impairment?. J Clin Neurophysiol. 2011 Dec;28(6):625-32. PubMed.
  4. Lathan C, Spira JL, Bleiberg J, Vice J, Tsao JW. Defense Automated Neurobehavioral Assessment (DANA)-psychometric properties of a new field-deployable neurocognitive assessment tool. Mil Med. 2013 Apr;178(4):365-71. PubMed.
  5. Cordell CB, Borson S, Boustani M, Chodosh J, Reuben D, Verghese J, Thies W, Fried LB, . Alzheimer's Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimers Dement. 2013 Mar;9(2):141-50. PubMed.
  6. Roach EB, Bleiberg J, Lathan CE, Wolpert L, Tsao JW, Roach RC. AltitudeOmics: Decreased reaction time after high altitude cognitive testing is a sensitive metric of hypoxic impairment. Neuroreport. 2014 Apr 9; PubMed.
  7. Spira JL, Lathan CE, Bleiberg J, Tsao JW. The impact of multiple concussions on emotional distress, post-concussive symptoms, and neurocognitive functioning in active duty United States marines independent of combat exposure or emotional distress. J Neurotrauma. 2014 Nov 15;31(22):1823-34. Epub 2014 Oct 9 PubMed.

External Citations

  1. 510k clearance
  2. trial
  3. HAND study
  4. Phase 2a trial
  5. company press release

Further Reading

Papers

  1. Snyder PJ, Jackson CE, Petersen RC, Khachaturian AS, Kaye J, Albert MS, Weintraub S. Assessment of cognition in mild cognitive impairment: a comparative study. Alzheimers Dement. 2011 May;7(3):338-55. PubMed.
  2. Brinkman SD, Reese RJ, Norsworthy LA, Dellaria DK, Kinkade JW, Benge J, Brown K, Ratka A, Simpkins JW. Validation of a self-administered computerized system to detect cognitive impairment in older adults. J Appl Gerontol. 2014 Dec;33(8):942-62. Epub 2012 Sep 18 PubMed.
  3. Jacova C, McGrenere J, Lee HS, Wang WW, Le Huray S, Corenblith EF, Brehmer M, Tang C, Hayden S, Beattie BL, Hsiung GY. C-TOC (Cognitive Testing on Computer): Investigating the Usability and Validity of a Novel Self-administered Cognitive Assessment Tool in Aging and Early Dementia. Alzheimer Dis Assoc Disord. 2014 Sep 1; PubMed.
  4. Tarnanas I, Tsolaki M, Nef T, M Müri R, Mosimann UP. Can a novel computerized cognitive screening test provide additional information for early detection of Alzheimer's disease?. Alzheimers Dement. 2014 Mar 18; PubMed.

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