Why we need cognitive testing in research

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We hear a lot about cognitive testing in the literature, but why is it so important at home, at the clinic and during trials research?

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In simplified terms, we can define cognition as a process of mental processing to acquire and relay information, particularly understanding through experience and senses. Cognitive ability is sometimes difficult to define and, since it underpins a whole host of brain conditions from neuropsychiatry to neurodegeneration, we need comprehensive tools with sufficient breadth to assess and monitor it.

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Neuropsychiatry and Neurodegeneration - What's the difference?

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The most prominent use cases of cognitive testing lie in the assessment of neuropsychiatric and neurodegenerative conditions. Neuropsychiatric conditions can include anxiety, stress, depression, mania, schizophrenia and obsessive compulsive disorder (OCD), and are not intimately tied to degeneration of nerve cells. Neuropsychiatry is underpinned by neurophysiological changes that affect our mood, emotion, perception of pleasure and displeasure. While these conditions can be phasic and can affect the wider population sporadically throughout life, they can also threaten life when they become chronic and long-term. For these reasons, cognitive testing and wellbeing monitoring are useful for the whole population, regardless of their participation in research, or any pre-existing or arising diagnoses.

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Neuropsychiatric mental states can apply to everyone at some point in their life and, at a molecular level, can be affected by neurotransmitters and neurotropic factors. Some of these you might be familiar with include BDNF, serotonin and dopamine. These factors, while important in the aetiology and presentation of neuropsychiatric conditions, also have weighting on neurodegeneration which we will talk about next.

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Neurodegeneration has rich genetic links, is often age- and inflammatory-mediated and, as the name suggests, is tied with the decline or death of cells in the nervous system milieu. Conditions including Alzheimer's Disease and Parkinson's Disease are some of the most common and we will all likely know of someone who has unfortunately been affected by these debilitating conditions.

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While these can also be impacted by neurotransmitters and neurotropic factors, the true pathology is much more molecularly and histologically apparent. In the case of Alzheimer's Disease, for example, this is very visually apparent in the form of peppered spots of amyloid-β in affected tissue as well as brain shrinkage. These striking features can sometimes make neurodegenerative conditions easier to characterise and diagnose.

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Why are cognitive tests so important?

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Over the last 10 years, reported cases of depression, stress and anxiety have soared and while they have been catalysed by world events including the COVID-19 pandemic, geopolitical instability, climate change concerns and war, metabolic co-morbidities including obesity, diabetes and auto-immune diseases are also playing their part in this multifaceted space.

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The "Causation : Causality" paradox between these conditions is difficult to understand, however evidence suggests from comprehensive epidemiological meta-analyses that these contributing factors are all closely linked. To add even greater complexity to our narrative, the cross-talk between stress, anxiety, depression and metabolic disorders also has roots in neurodegeneration.

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In fact, neuropsychiatric conditions and metabolic disorders are now recognised as risk factors for neurodegenerative disorders. Dementias including Alzheimer’s Disease and Parkinson’s Disease are dramatically on the rise and co-presentation with obesity, diabetes, depression and stress are now commonplace. Figures by the Alzheimer’s Society suggest that there are more than 850,000 cases in the United Kingdom alone, some 50 million cases worldwide and this number is increasing every day.

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For a whole host of reasons, cognitive and neuronal decline and poor wellbeing can potentially impact upon the entire human population. Whether it's in an established disease-setting, or in otherwise perfectly healthy people, cognitive monitoring is crucial to providing useful data which can support good health and improved quality of life. Our brains are truly unique and we have a growing repertoire of tests (digitally and questionnaire-based) at our disposal to explore their depths. These tools are instrumental in assessing health in all walks of life, and here's what they can do.

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Cognitive Tests: Which ones to use - and why?

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We can compartmentalise cognitive tests into specific areas of focus which have key interaction with certain functions and locality in the brain. Through extensive validation in the literature, we now know which tests are sensitive to which facets of biology and brain functionality. They can test a whole host of regions of the brain, including areas essential for executive function, attention and memory.

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Executive Function

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A battery of tests including the Stroop Test, Wisconsin Card Sorting Test (WCST) and Trail Making Test (to name a few) can help assess working memory and attention control as part of executive function. By presenting participants with combinations of colours, shapes and words, they are challenged to select a correct response which is often not what is expected. Response Inhibition tests which challenge inhibitory control are also effective in assessing executive function. For example, the participant might press a series of buttons which are expected to be correct. However, every so often something unexpected appears and the participant must mentally reconcile this and refrain from answering incorrectly.

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Challenging participants in these ways enables us to monitor performance in a variety of research settings including epilepsy, neurodegeneration, depression and anxiety, traumatic brain injury (TBI) and more.

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Attention and Processing Speed

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Tests including eminent behaviourist Burrhus Frederic Skinners Match-To-Sample (MTS) have been pivotal in assessing attention and short-term memory. These tests require the participant to match a particular pattern or visual to similar-looking patterns or visuals. The participant must identify which pattern they are already familiar with to score correctly. Rapid Serial Visual Processing (RSVP) is also an effective test to assess attention and processing speed. First developed by internationally renowned MIT psychologist Mary Potter, these tests present participants with a correct serial code which they must identify from a stream of stimuli which will sporadically present this target code. This code can take the form of visuals, digits or words, but will always be mixed amongst other material which the participant must identify it from. The MTS and RSVP tests are particularly sensitive when assessing depression, neurodegenerative conditions, epilepsy and autism.

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Memory

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Memory is a complicated process which defines the way in which information is encoded, stored and recalled. Conditions which are very susceptible to memory loss (including dementias such as Alzheimer's Disease) are very sensitive to memory testing. Common tests include Digit Span where the participant is challenged to remember increasingly longer sequences of numbers. In this way, the threshold of their memory is being challenged and, assuming basic numeracy skills, this enables reproducibility in many different target groups. Modifications on Skinners' Match-To-Sample experiments have also been introduced to create a greater challenge on human memory. These Delayed Match-To-Sample are very similar, however, allow enough time to pass as to introduce greater challenge and assess the participants ability to retain this information in their working memory.

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Mental Status

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Perhaps the most commonly used tool in neuronal decline assessment is the Mini-Mental State Examination (MMSE). Since it's creation in 1975 by Folstein and colleagues, it's been incredibly useful as a diagnostic tool. MMSE is a 30-point test, designed specifically to test cognitive impairment by addressing a number of key functions including recall, language and attention. Low test scores strongly indicate cognitive impairment, and the multi-functionality of the test allows for differentiation between different types of dementia. For example, Alzheimer's Disease patients score very poorly on orientation to time and space tasks and recall. MMSE has been instrumental in monitoring and supporting diagnosis of neurodegenerative conditions.

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Some readers may also be familiar with the Montreal Cognitive Assessment (MoCA) and revised Addenbrooke's Cognitive Examination (revised, ACE-R) tests which are also commonly used alongside or in-place of MMSE.

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Other Tools

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Non-interactive tests are also incredibly useful for the assessment and monitoring of depression, stress, anxiety and similar neuropsychiatric conditions. These include the Scale of Positive and Negative Experience (SPANE), Positive and Negative Affect Schedule (PANAS) and General Anxiety Disorder-7 (GAD-7).

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Combinations of these tools have become very powerful when assessing overall health, mental wellbeing and cognitive function and it is becoming increasingly important for wellbeing and quality of life metrics to be taken at trial alongside other data pertinent to the research question.

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The Trialflare platform is able to obtain a variety of these measurements using holistic interactive and non-interactive approaches. These tests can be run at a clinic, or, for greater flexibility, our mobile app can be used off-site in a decentralised manner. If you have any questions regarding our repertoire of cognitive and wellbeing tests, please get in touch at help@trialflare.com and we will get back to you shortly.