NIH Test Can Detect Cognitive Changes in Young People With Fragile X

NIH Toolbox Cognition Battery may help guide treatment decisions

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by Steve Bryson, PhD |

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The NIH Toolbox Cognition Battery (NIHTB-CB) test accurately detects developmental changes in cognitive function among young people with intellectual disabilities, including those with fragile X syndrome, a study reports.

Matching, or even exceeding, the changes detected in a standard IQ test over two years, the NIHTB-CB is a promising option to evaluate the effects of new investigational therapies for intellectual disabilities in clinical trials.

“These findings may help to guide us in terms of where intervention would be the most effective or beneficial,” David Hessl, PhD, the study’s senior author and a professor at the University of California (UC) Davis, said in a university press release.

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People with developmental disabilities often excluded from research studies

The study, “Sensitivity of the NIH Toolbox to Detect Cognitive Change in Individuals With Intellectual and Developmental Disability,” was published in the journal Neurology.

Fragile X syndrome is the most common cause of inherited intellectual disability, generally characterized by an IQ of about 70 or below. Finding tools to accurately measure intellectual disability to evaluate the effect of new therapies in clinical trials is challenging.

“People with lower developmental abilities are often excluded from research studies and clinical trials,” said Hessl, who also works at the UC Davis MIND Institute. “That means the results of those studies do not apply to everyone, and this entire group is left out from having the potential benefit of a treatment.”

The NIHTB-CB is administered by computer or tablet using a battery of brief tasks to assess attention, working memory, and language. Tasks include comparing two pictures and deciding if they are the same, listening to words and pointing to a matching picture, or placing images from a story in the correct order.

Hessl and colleagues at the UC Davis MIND Institute and other institutions evaluated NIHTB-CB’s sensitivity to detect developmental changes in people with intellectual disabilities against the Stanford-Binet intelligence scales – 5th edition (SB5), a long-established IQ test.

These findings may help to guide us in terms of where intervention would be the most effective or beneficial

Two-year intellectual growth was evaluated for 197 participants

Although SB5 is often used in clinical studies, many researchers dislike repeating IQ tests over short periods of time.

“There can be practice effects for some IQ test components, as well as an emphasis on acquired knowledge-type questions,” Hessl said. “For an outcome measure, you want something with more fluid and easily changeable components, like the NIHTB-CB.”

Both tests were administered to 256 individuals, ages 6–27 years: 78 with fragile X, 92 with Down syndrome, and 86 classified as having other intellectual disabilities. A total of 197 participants were re-tested after two years. Two-year intellectual growth was evaluated at three age points: 10, 16, and 22 years.

“We knew that a substantial portion of young people would be making gains in cognition during this period, and we could use that opportunity to see if the Toolbox picked up on those developmental changes,” said Hessl. “Before using a measure in clinical trials, it is really important to learn whether it is sensitive to change.”

Results showed that NIHTB-CB-detected intellectual growth over two years was comparable to, or exceeded, that measured with the reference-standard measure, SB5. The growth patterns in intellectual development for each patient group, as assessed with NIHTB-CB, also matched their SB5 growth results.

All groups showed significant intellectual gains at 10 years of age on both tests, except for NIHTB-CB’s reading test — in which fragile X patients showed no significant change at any of the age points.

Two-year cognitive growth at ages 16 and 22 varied between groups, but it was largely absent in people diagnosed with fragile X and mostly pronounced among those with Down syndrome.

Compared with participants with other intellectual disabilities, those with fragile X showed delayed improvement in attention and inhibitory control (self-controlled behavior), while Down syndrome patients had delayed growth in receptive vocabulary (understanding words).

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Young adults with Down syndrome show improvement

In sharp contrast to patients in the other two groups, young adults with Down syndrome showed significant gains in attention and inhibitory control, as well as working memory.

All participants showed little improvement in cognitive flexibility, or the ability to adapt to new rules or environments.

At their first visit, fragile X male patients had lower cognitive performance than female patients on SB5 and on most tasks of NIHTB-CB, while no sex differences were seen in the other groups.

These findings highlighted that “the NIHTB-CB is sensitive to developmental changes in individuals with ID [intellectual disability],” the researchers wrote, adding that it has the “potential to identify meaningful trajectories across cognitive domains and ID [conditions].”

“Sensitivity to change within the context of treatment studies and delineation of clinically meaningful changes in NIHTB-CB scores, linked to daily functioning, must be established in future research to evaluate the battery more completely as a key outcome measure,” they added.

Hessl noted that NIHTB-CB may also be used in the clinic or in schools to gauge intellectual growth.

“I think we have strong evidence that the NIH Toolbox Cognition Battery does detect changes in cognition over time,” Hessl said. “It’s not universal – not for every single subtest with all the groups that we studied – but there was enough evidence across the groups and the different tests that it’s picking up on some important elements of change.”