Institute for Behavioral Genetics

Detecting cognitive decline before its symptoms start

Rachel Sauer — Wed, 13 Nov 2024 20:24:58 +0000

Detecting cognitive decline before its symptoms start Rachel Sauer Wed, 11/13/2024 - 13:24

Daniel Long

In his research on the brain, Daniel Gustavson looks for clues about when cognitive decline begins

According to Daniel Gustavson, assistant research professor in the Institute for Behavioral Genetics, much of the research on cognitive decline starts late.

“A lot of studies of older adults—too many, in my opinion—focus on when some cognitive decline has already happened,” he says. “It's clear that a lot of the disease, or even just normal aging, has already taken place by the time somebody comes into a clinic and says, ‘I'm worried about my brain.’”

Gustavson wants to dig deeper into the timeline and see if cognitive decline can be spotted before its telltale signs arise. A paper he coauthored and recently published in Neurobiology of Aging makes headway toward accomplishing that goal.

ŷ��ڱ��Ƶ Boulder researcher Daniel Gustavson notes that a lot of cognitive decline, or even just normal aging, has already taken place by the time "somebody comes into a clinic and says, ‘I'm worried about my brain.’”

The cognitive gas tank

Gustavson’s study—which used twin research, genetic analysis and magnetic resonance imaging (MRIs), among other methodologies—examines the relationship between brain reserve in middle age and executive function later in life.

“Brain reserve,” says Gustavson, “is a bit like a gas tank. You have a certain amount of gas built up when you’re a young adult, when your brain is at its healthiest, and as you age, you start to lose some of that fuel.”

Executive function, he adds, refers to complex goal management or attentional control. “It captures higher-level cognitive processes, where you have to be controlling other sub-processes.”

An example of executive function in action is asking someone to memorize and reorder a string of letters and numbers.

“You might have people listen to a list like X, six, B, Y, seven, J, and then they’d have to remember that list in their head and repeat the numbers back in numerical order and the letters in alphabetical order,” Gustavson says. “It’s a little more complicated than just repeating what someone said.”

Using data from the Vietnam Era Twin Study of Aging (VETSA), which includes more than 1,600 subjects who have undergone various cognitive assessments at regular intervals over the past 20 years, Gustavson and his coauthors concluded that higher brain reserve at the age of 56 was associated with better executive function at the age of 68.

Looks can be revealing

Brain reserve, says Gustavson, is a proxy for brain thickness, and brain thickness is determined through MRIs.

To analyze the hundreds of MRIs of VETSA subjects, Gustavson and his coauthors used a machine-learning algorithm developed by James H. Cole, professor of neuroimage computing at the MANIFOLD Lab, which was trained in much the same way Google trains its search algorithms.

“You can train it over and over again,” Gustavson says. “The more data you have”—that is, MRIs—“and the more times you tell it, ‘You were wrong this time. You were right this time,’ the better it gets at classifying this brain as one age versus that brain as another age.”

The algorithm assesses plump, padded brains as younger and atrophied, motheaten brains as older, regardless of the chronological age of the people in whose heads those brains reside. That means, for example, that a 56-year-old can have a brain that appears 60 and a 60-year-old can have a brain that appears 56.

And this matters, Gustavson says, because how a brain looks in an MRI predicts its executive function years later.

“Controlling for their actual age, people with younger-looking brains had much shallower decline in executive function over the subsequent 12 years, and people whose brains appeared older than average had steeper drops in executive function.”

Yet the cause of this discrepancy—genetics? environment? trauma?—is something the algorithm alone can’t explain. That’s where twin research comes in.

Same genes, different story

One of the benefits of twin studies like VETSA, Gustavson says, is their ability to separate environmental influences on a person’s health—things like diet, exercise and place of residence—from genetic influences.

“Brain reserve is a bit like a gas tank. You have a certain amount of gas built up when you’re a young adult, when your brain is at its healthiest, and as you age, you start to lose some of that fuel,” says Daniel Gustavson. (Illustration: iStock)

“Those two things aren't fully separable, but basic twin studies give us some idea of how inherited different constructs are—not only cognitive abilities, like memory or speed, but also changes in those abilities. Twin studies help us quantify how much those changes are due to genetics and how much are due to environment.”

If one twin experiences cognitive decline faster than the other, in other words, researchers can confidently point to environment as the reason, since twins share the same genes.

But twin studies can go only so far, Gustavson says, as they tend to paint with a broad brush. “You often can't pinpoint specific genes or specific environments that matter, because it's all statistical.”

That’s why Gustavson and his team incorporated genetic analyses in their study. They wanted a higher-resolution snapshot of the genetic influences on cognitive decline, specifically by seeing if the APOE genotype, which is strongly associated with Alzheimer’s, predicted a drop in executive function.

What they found is that, although APOE alone did not fully explain changes in subjects’ executive function over time, those subjects’ genes taken as a whole did.

“Most of the association between people's brain health and their future cognitive decline, about two-thirds, was explained by genetics,” Gustavson says.

But that’s not to dismiss the other third as inconsequential.

“Things like healthy lifestyle, diet, smoking and alcohol use, social engagement—those things don't seem like they relate to cognitive changes, but they might impact your brain health in the first half of your life, and then your brain health in midlife will impact your cognition later,” says Gustavson.

The fourth wave

Gustavson and his fellow researchers just completed the fourth wave of data collection, when the VETSA subjects were 74 years old, and are therefore currently working to build upon their findings.

“We would like to expand our models to capture the cognitive changes even further out,” he says.

Gustavson would also like to deepen his understanding of what exactly the brain-age algorithm is detecting. “Is it capturing something new to midlife, or is it capturing something from young adulthood, the consequences of which are only becoming apparent in midlife?”

He suspects it’s the latter, but he’s not yet sure. “I really want to look at that in more detail.”

Jeremy A. Elman, Chandra A. Reynolds, Lisa T. Eyler, Christine Fennema-Notestine, Olivia K. Puckett, Matthew S. Panizzon, Nathan A. Gillespie, Michael C. Neale, Michael J. Lyons, Carol E. Franz and William S. Kremen contributed to this research.

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In his research on the brain, Daniel Gustavson looks for clues about when cognitive decline begins.

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ADHD and reading disability often occur together, study finds

Anonymous — Thu, 17 Oct 2024 14:56:38 +0000

ADHD and reading disability often occur together, study finds Anonymous (not verified) Thu, 10/17/2024 - 08:56

Daniel Long

It’s surprisingly common for children to have both conditions, ŷ��ڱ��Ƶ Boulder researcher Erik Willcutt argues in a recently published paper

According to a paper coauthored by Erik Willcutt, professor of psychology and neuroscience at the University of ŷ��ڱ��Ƶ Boulder and faculty fellow of the Institute for Behavioral Genetics, many children with attention-deficit/hyperactivity disorder (ADHD) also have reading disability, and vice versa.

“A lot of kids tend to have both learning and attentional difficulties,” says Willcutt, a clinical child psychologist by training. “Similarly, many children with reading disability also experience broader learning difficulties in areas such as math and writing.”

This research marks a shift in the clinical understanding of learning disabilities.

In recently published research, Erik Willcutt, a ŷ��ڱ��Ƶ Boulder professor of psychology and neuroscience, finds that many children with attention-deficit/hyperactivity disorder also have reading disability, and vice versa.

“Twenty-five years ago, we all went into an assessment with a child thinking we had to figure out what the diagnosis is.”

“The” diagnosis—singular.

“Back then, it was always kind of surprising if a child met criteria for more than one diagnosis. We’d think, ‘Maybe we’re just wrong, and we’ve got to figure out which diagnosis is correct.’”

Yet, as research has progressed, this either-or thinking has transformed into something more like both-and thinking.

“We’ve realized over time, there are a lot of kids that really do seem to have more than one diagnosis, and that in many cases both diagnoses would benefit from treatment.”

When one diagnosis complicates another

The phenomenon of multiple diagnoses for one person is called comorbidity, a term “that came out of classic medical literature where people could have more than one illness at the same time,” says Willcutt. “For example, heart disease frequently co-occurs with other physical conditions such as diabetes, and this may mean that treatment of the heart disease is complicated by the diabetes or another co-occurring illness.”

It’s the same idea with reading disability and ADHD. “That comorbidity suggests that a child's difficulties extend beyond what they would be if that child had just reading disability.”

Reading disability, Willcutt points out, doesn’t simply mean difficulty reading. It means unexpected difficulty reading, with the expectations being based on a child’s education.

So, a child who struggles to read but hasn’t had an adequate reading education may not have reading disability. Perhaps that student struggles because he or she hasn’t grown up around books, or hasn’t been read to, or hasn’t been given adequate reading instruction. For a student such as this, difficulty reading may not be a disability so much as the natural consequence of a less-enriched reading environment.

It's the children who have had an adequate education and still underachieve in reading who may have reading disability. And if those kids also happen to have ADHD, their reading disability will likely be harder to manage, just as heart disease becomes more challenging for someone who also has diabetes.

“Individuals with more than one disorder often differ in important ways from individuals with a disorder in isolation, with the comorbid group frequently experiencing greater symptom severity, more extensive and severe functional and neurocognitive impairment, and poorer long-term outcomes,” Willcutt and co-author Stephen A. Petrill state in their paper.

Externalizing and internalizing behaviors

Researcher Erik Willcutt notes that reading disability doesn’t simply mean difficulty reading. It means unexpected difficulty reading, with the expectations being based on a child’s education.

There is a range of behaviors associated with reading disability and ADHD, Willcutt explains, some of which are “externalizing” and some of which are “internalizing.”

Externalizing behaviors are those that children express outwardly—“things like aggression, delinquency or conduct problems,” says Willcutt—whereas internalizing behaviors “are more internally focused—so if you feel anxious or you feel depressed or withdrawn.”

Willcutt says that reading disability and ADHD frequently co-occur with both internalizing and externalizing behaviors, but the specific profile varies among children. One student with comorbid ADHD and reading disability may continually show up late to school and disrupt class, whereas another student with the same diagnoses may be quiet and anxious.

“And there are some different behavior clusters that seem to really matter,” Willcutt adds. “The kids who have reading disability and ADHD along with early aggressive or delinquent behaviors tend to be a subgroup that is at higher risk for more severe antisocial behaviors during adolescence. On the other hand, students who have ADHD and reading disability along with internalizing symptoms often show pronounced difficulties in the classroom because they are really anxious about their academic performance.”

Assessment and treatment

Willcutt says that one key takeaway from his and Petrill’s study is that comorbidity matters and is much more common than previously thought. “At least 25% of kids who have ADHD have a learning disability, which is much higher than we would expect by random chance.”

Willcutt therefore hopes those who read his and Petrill’s study, particularly clinicians, adjust their assessment practices in a way that addresses the potential for comorbid diagnoses.

We’re at the point of saying when a child has ADHD and reading disability, both conditions really warrant interventions. Rather than trying to decide which is more important, we should really target both of them by providing the optimal intervention for reading disability and the optimal intervention for ADHD.”

“If you’re assessing learning disabilities, it’s really important to also assess whether a child has attention problems, anxiety or conduct difficulties along with that. For clinicians who specialize in the assessment of ADHD, it's critical to include a screening measure to determine whether the child may also have learning problems. Our results suggest that it may matter quite a bit if they have a comorbid diagnosis.”

For the field more broadly, Willcutt hopes that his and Petrill’s work prompts other researchers to study treatments for comorbid learning disabilities and attentional difficulties.

“We’re at the point of saying when a child has ADHD and reading disability, both conditions really warrant interventions. Rather than trying to decide which is more important, we should really target both of them by providing the optimal intervention for reading disability and the optimal intervention for ADHD.”

In other words, if a child has both reading disability and ADHD, treating only one will likely have little to no effect on the other.

“Reading intervention might really help with the reading, but it may not address some of the other concerns that are also getting in the way for that child.”

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It’s surprisingly common for children to have both conditions, ŷ��ڱ��Ƶ Boulder researcher Erik Willcutt argues in a recently published paper.