A new behavioral test to detect early Alzheimer’s risk

Summary: Researchers have developed a simple behavioral test to measure an individual’s risk of developing Alzheimer’s disease before symptoms appear.

Source: CalTech

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 affects more than 6 million Americans, most of whom are 65 or older. Although the neurological damage from the disease is irreversible, early detection and intervention have been shown to slow its progression.

Before the physical symptoms of Alzheimer’s appear, the most common method of measuring a person’s risk of developing the disease is to measure the levels of certain proteins, such as beta amyloid and tau, in the spinal fluid . This test is invasive, painful and expensive.

Now, a team at 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 before any symptoms appear.

An article describing the team’s findings appears in the journal Alzheimer’s and dementia: diagnosis, assessment and monitoring of the disease on September 20.

The research was conducted in the laboratory of Shinsuke Shimojo, the Gertrude Baltimore Professor of Experimental Psychology. Shimojo is an Affiliate Professor at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.

“Early detection of Alzheimer’s disease is important to take interventions that can slow the progression of the disease,” says the study’s first author, Shao-Min Sean Hung, formerly a postdoctoral researcher in the Shimojo lab and now an assistant professor at Waseda University. in Japan

“Prior to the onset of illness, by definition, cognitively healthy people do not have behavioral symptoms, and so traditional behavioral assessments of illness are not possible because behavioral symptoms are not yet present.

“What we’re trying to do is develop a test to detect behavioral abnormalities long before symptoms appear and in a less invasive way than measuring spinal fluid.”

The study involved 40 people with an average age of 75, all cognitively healthy, who underwent a myriad of tests related to Alzheimer’s risk: magnetic resonance imaging (MRI) of the brain, genome sequencing, and the invasive spinal fluid measurements mentioned above.

Based on these biological markers, individuals could be classified as high risk or low risk. The researchers aimed to develop a behavioral test whose results would correlate with these biological measures.

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, 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 the color green.

At each iteration of the task, the participant is asked to name the color of the word or the word itself. Compared to naming the word itself, naming the color of the text is considered “high effort”; it is more difficult than it seems.

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

The colorless word is intended to unconsciously distract the participant and measure “implicit cognition.” In addition to conscious and intentional information gathering or ‘explicit cognition’, our brain has a separate system in which sensory information is digested without conscious awareness, this is known as implicit cognition.

“Participants in our study are cognitively healthy at an explicit level, and we measure this using a battery of neuropsychological tests,” says Hung.

An example of a 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. Credit: Caltech

“But the central question of this study is: What about their implicit cognition? Could it be possible that their implicit cognition is more sensitive to show Alzheimer’s-related cognitive decline? The study tested the hypothesis that participants healthy high-risk and low-risk cognitive subjects will be distracted by an invisible word differently.”

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

The test showed that individuals with high-risk biological factors were about 4 percent slower on the Stroop test when shown an unconscious, inconsistent word.

This suggests, says Hung, that the conditions leading to Alzheimer’s may affect implicit cognition long before conscious cognition, and so a test to measure implicit cognitive performance may be able to detect a high risk of developing the Alzheimer’s disease without the need for invasive physical measurements. .

See also

This shows a woman

The researchers stress that this test is not yet diagnostic, meaning that this particular test cannot measure an individual’s risk of developing Alzheimer’s, but simply shows a correlation between the group of high-risk individuals and a worse performance on the test when an unconscious word distractor occurs. present

The next steps are to combine the test with other non-invasive physical measurements, such as heart rate and other neurophysiological markers, with the aim of making it more predictive.

Other Caltech co-authors are Shimojo and senior scientist Daw-An Wu, Ph.D. Professor Xianghong Arakaki of the Huntington Institutes of Medical Research is an additional co-corresponding author.

About this Alzheimer’s disease research news

Author: Lori Dajose
Source: CalTech
Contact: Lori Dajose – CalTech
Image: Image credited to CalTech

Original research: Open access
“Stronger implicit interference in cognitively healthy older participants at increased risk of Alzheimer’s disease” by Shao-Min Hung et al. Alzheimer’s and dementia: diagnosis, assessment and monitoring of the disease


Stronger implicit interference in cognitively healthy older participants at increased risk of Alzheimer’s disease


Cerebrospinal fluid abnormal beta amyloid (Aβ)42 and tau levels have been revealed decades before the onset of Alzheimer’s disease (AD) symptoms; however, the exam is usually invasive and inaccessible to most people. Thus, we aimed to develop a noninvasive behavioral test that targets potential early cognitive changes to measure cognitive decline. Specifically, we hypothesized that cognitively healthy older participants would perform comparable when the task was explicit and dependent on conscious cognition. However, when the task was implicit, the performance of participants at high and low AD risk bifurcated. That is, early changes in unconscious cognition could be related to cognitive health.


We measured implicit interference elicited by an imperceptible distractor in cognitively healthy older participants with normal (low risk) and pathological (high risk) Aβ.42/total tau ratio. Participants had to perform a Stroop task (word naming or color naming in a word inconsistent with ink semantics) with a visually masked distractor presented before the target task.


We found that, under a high-effort task (i.e., color naming in the Stroop task), high-risk participants suffered interference when the imperceptible distractor and subsequent target were incongruent in their responses they triggered Their reaction times were reduced by approximately 4%. This implicit interference was not found in low-risk participants.


These findings indicate that weakened inhibition of implicit distractor information may be a potential behavioral biomarker for early identification of AD pathology. Thus, our study provides a new experimental paradigm to reveal early pathological aging by assessing how individuals respond to subperceptual threshold visual stimuli.

Leave a Reply