Team from Caltech and Huntington Medical Research Institutes announce progress on behavioral test to detect early risk of Alzheimer’s disease

A sample Stroop Paradigm test. It takes a little extra mental effort to name the color of a word when it doesn’t match the word itself.
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Alzheimer’s disease is a neurodegenerative disease that damages a person’s ability to think, remember and perform basic functions. According to the National Institutes of Health, Alzheimer’s disease affects more than 6 million Americans, mostly aged 65 and older. Although the neurological damage of the disease is irreversible, early detection and intervention have been shown to slow its progression.

Before the onset of physical symptoms of Alzheimer’s disease, the most common method used to measure the risk of developing the disease is to measure the levels of certain proteins, such as beta-amyloid and tau proteins, in the fluid cerebrospinal. This test is invasive, painful and expensive.

Now, a team from Caltech and the Huntington Institutes of Medical Research has made progress toward developing a simple behavioral test to measure an individual’s risk of developing Alzheimer’s disease before any symptoms appear.

The research was conducted in the lab of Shinsuke Shimojo, Gertrude Baltimore Professor of Experimental Psychology. An article describing the results appears in the journal Alzheimer’s and dementia September 20. Shimojo is an affiliate faculty member of the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.

“Early detection of Alzheimer’s disease is important in order to take interventions that can slow disease progression,” says study first author Shao-Min Sean Hung, a former postdoctoral researcher at the Shimojo lab and now assistant professor at Waseda University. in Japan. “Before disease onset, by definition, cognitively healthy people do not show behavioral symptoms – and so it is not possible to do traditional behavioral assessments for disease because there are not yet What we’re trying to do is develop a test to detect behavioral abnormalities long before any symptoms appear and in a way that’s less invasive than measuring cerebrospinal fluid.

The study involved 40 people with an average age of 75 and all in good cognitive health, who underwent a myriad of tests linked to Alzheimer’s risk: magnetic resonance imaging (MRI) of the brain, genome sequencing and measurements invasive cerebrospinal fluid mentioned above. Based on these biomarkers, individuals could be categorized as high risk or low risk. The researchers aimed to develop a behavioral test whose results would correlate with these biological measurements.

The team developed a task in which a participant undergoes a so-called Stroop Paradigm test. In this common test, a person is shown a word – the name of a color – displayed in colored ink. However, the word itself does not necessarily match the color of the printed word. For example, the word “RED” is printed in green. At each iteration of the task, the participant is asked to name either the color of the word or the word itself. Compared to naming the word itself, naming the text color is considered “high effort” – it’s harder than it looks. (You can try it yourself below.)

In this study, the researchers also added a hidden element to the Stroop paradigm. Just before the actual target is displayed, a colorless word rapidly flashes across the screen, so rapidly that a participant cannot consciously detect it.

The colorless word is intended to subconsciously distract the participant and measure “implicit cognition”. In addition to conscious and intentional collection of information or “explicit cognition”, our brain has a separate system in which sensory information is digested without consciousness – this is called implicit cognition.

“Participants in our study are cognitively healthy at the explicit level, and we measure this through a battery of neuropsychological tests,” Hung says. “But the central question of this study is: what about their implicit cognition? Could it be that their implicit cognition is more sensitive to show the cognitive decline linked to Alzheimer’s disease? The study tested the hypothesis that high-risk and low-risk cognitively healthy participants would be distracted differently by an invisible word.

The study was double-blind, so neither the participants nor the researchers knew anything about the participants’ biological data prior to data analysis.

The test showed that people with high-risk biological factors slowed down by around 4% on the Stroop test when an unconscious and incoherent word was displayed. This suggests, says Hung, that the conditions that lead to Alzheimer’s disease may affect implicit cognition long before conscious cognition, and so a test to measure implicit cognitive performance may be able to detect an elevated risk of developing the disease. Alzheimer’s disease without the need for invasive physical measures. .

The researchers point out that this test is not yet diagnostic, i.e. this particular test cannot measure a people risk of Alzheimer’s but simply shows a correlation between the band high-risk individuals and poorer test performance when an unconscious distracting word is present. The next steps are to combine the test with other noninvasive physical measurements, such as heart rate and other neurophysiological markers, with the aim of making it more predictive.

The article is titled “Strongest implicit interference in cognitively healthy older participants at higher risk for Alzheimer’s disease.” Other Caltech co-authors are Shimojo and lead scientist Daw-An Wu (PhD ’06). Professor Xianghong Arakaki of the Huntington Institutes of Medical Research is an additional co-corresponding author. Funding was provided by the James Boswell Postdoctoral Fellowship and the Caltech Biology and Biological Engineering Division Postdoctoral Fellowship, the Whittier Foundation, and the National Institutes of Aging.

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