IQ After Pediatric Concussion; Hearing Aids and Dementia Progression

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include the benefits of “weekend warrior” exercising, an interfering RNA for blood pressure, the impact of concussion on IQ in kids, and hearing aids and dementia.

Program notes:

0:40 Interfering RNA and hypertension

1:42 Injected to interfere with angiotensinogen

2:43 Have knocked it out before

3:24 Hearing aid use and dementia progression

4:24 Two groups recruited

5:24 In those with more risk factors it helped

6:21 Not at risk doesn’t really help

6:51 Benefits of exercise just on weekends

7:51 90,000 individuals, 30,000 active

8:51 Can concentrate activity

9:22 IQ after pediatric concussion

10:20 No clinically meaningful reductions

11:20 British football association study

12:00 End

Transcript:

Elizabeth: Does concussion have any impact on IQ in kids?

Rick: Affecting RNA to treat hypertension?

Elizabeth: Do hearing aids help with regard to the development of dementia?

Rick: And is it healthy to be a weekend warrior?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean at the Paul L. Foster School of Medicine.

Elizabeth: Rick, I would like to turn first to the New England Journal, if you’re okay with that — this hormone angiotensinogen and, gosh, what’s it have to do with hypertension?

Rick: Well, Elizabeth, it has a lot to do with hypertension. Angiotensinogen is actually made in the liver and it’s processed by a number of different enzymes, renin-angiotensin converting enzymes, and these particular compounds are responsible for retaining water and causing constriction of the blood vessels, all of which can increase blood pressure.

We have things like ACE inhibitors and angiotensin receptor blockers that are currently on the market to address this. This is a novel way of addressing not the subsequent products of the pathway, but the angiotensinogen.

What this is, it’s a study using RNA interference to affect the production of angiotensinogen at the level of the liver. What RNA interference does is, it attaches small pieces of RNA to a molecule. The molecule enters the liver and it prevents the production of angiotensinogen so the protein is really never made.

In this particular study, a phase I study, so it’s an initial dosing study, they use doses as little as 10 mg to as much as 800 mg. By the way, it’s injected, it’s followed for 4 weeks and up to 24 weeks to see whether it causes reduction of the protein, is this safe, and more importantly is, can it reduce blood pressure?

What it did show is that it effectively reduces angiotensinogen production by more than 90%. And in people with hypertension, it lowered their blood pressure substantially, even 24 weeks after a single injection.

More specifically, it lowered the systolic blood pressure by more than 20 mm and the diastolic pressure by more than 10 mm. By the way, there weren’t any serious side effects in the 107 patients in whom the drug was tested.

Elizabeth: This sounds, of course, like really great news. I guess I would just call out that RNAs are just darlings of research right now, aren’t they? All the different types that we have out there that we ignored for a very long time.

Let’s talk a little bit about something we started to talk about before we were recording, which is, gosh, angiotensinogen. I’m just guessing that once we knock it out, we’re going to find out that there is more to that cat than we thought.

Rick: Well, we’ve already knocked out some of the other products in the pathway and we know that if we give too much, it can cause hypotension or low blood pressure. It can cause elevated potassium. As you noted, this is a small study in a small number of patients, none of whom had significant comorbid disease. These are relatively “healthy” people with hypertension. But for proof of concept, I think it’s very good to be able to give a one-time injection and have reduction in blood pressure over the course of 24 weeks is pretty impressive. Now, as you mentioned, sometimes that may be harmful in some other conditions. There is really a lot more we need to discover about this particular drug.

Elizabeth: Let’s turn from here to The Lancet. This is a Johns Hopkins study, actually, by my friend and colleague Frank Lin et al. This is taking a look at what Frank has been working on for many, many, many years. It’s something that’s called the ACHIEVE study, a multicenter, parallel group, unmasked, randomized controlled trial of adults who were between 70 and 84 years of age with untreated hearing loss and without substantial cognitive impairment at the time that they were enrolled in the study. This took place at four community study sites across the U.S.

They ended up randomly assigning 490 people to a hearing intervention, and 487 to a health education control group. There were two groups of folks who were represented in this: [first], those who were already part of a study that’s been ongoing for quite a while looking at cardiovascular health, called the ARIC study, the Atherosclerosis Risk in Communities study. Then they also recruited what they called healthy de novo, or new, community volunteers.

There were folks of both of those groups who were in each of the groups: the intervention group and in the health education group. In the intervention group, they were assessed and then they were given hearing aids. Then in the health education group, they basically had education.

They followed these folks out to see whether or not there were any differences in their 3-year cognitive decline. The answer was No. In spite of the fact that some folks were using hearing aids, it did not reduce their cognitive decline in the 3 years that they were followed. However, in those adults who were at risk for cognitive decline, a subanalysis seems to suggest that it might be helpful.

Rick: As you mentioned, in the overall analysis — the total cohort combined both study groups — it showed no effect. But there was a 50% reduction in global cognitive decline in the ARIC cohort. Now, the ARIC cohort had more risk factors for cognitive decline and dementia. They had lower baseline cognitive scores and a faster rate of decline. This suggests that the hearing intervention might differ in its effect. If people are at low risk, then it’s probably not very helpful. But in individuals that are older, at an increased risk, it might have a very important effect.

We know that dementia is increasing worldwide, especially in low- and middle-income countries, and we’re looking at ways of preventing it or modifying it that are really cost-effective. This shows that addressing hearing issues, especially in the highest-risk individuals, may be most helpful.

Elizabeth: I just have to wonder whether waiting for people to be at risk is really a good strategy for prevention.

Rick: The study would suggest that people that aren’t at high risk or have a low rate of decline, it’s really not going to be very helpful. Therefore, you’re basically applying a treatment that really doesn’t change the outcome of the particular group. That’s why I think this particular study is really informative.

Elizabeth: It seems to me that people who are experiencing hearing loss experience an improved quality of life when their hearing is bolstered by hearing aids.

Rick: That’s an important point, but a different outcome. If you can show that the hearing intervention improves their quality of life, then you can target those individuals in whom they have experienced a decrease in quality of life and want to improve it.

Elizabeth: Let’s turn to JAMA. Gosh, if you are a weekend warrior, are you putting yourself at risk?

Rick: Elizabeth, I’m really glad they did this study because when we look at the exercise recommendations, for many of us it’s hard to meet them. For example, we know that the guidelines recommend 150 minutes or more of moderate to vigorous physical activity per week to receive an overall robust health benefit.

Now, let me take a step back and say that any amount of exercise is helpful, so even individuals that can’t do 150 minutes shouldn’t be discouraged. Whatever you can do, it’s more important to be active than to sit. But for those of us who really want to try to meet the deadline and have a very busy job, we can’t actually do 30 minutes of exercise 5 days per week. The question is, is doing this weekend warrior, where you concentrate all your activity in 1 or 2 days, is as beneficial as spreading it out over the course of the week?

They looked at almost 90,000 individuals. They were in the UK Biobank cohort study. A significant number of those actually had accelerated-based physical activity data, so they wore a tracker so we can tell when they exercise. Of these 90,000 individuals, about a third of them were inactive. But of the two-thirds that were active, most of them were actually weekend warriors. About two-thirds of those were weekend warriors; a third of those provided regular activity that was spread out through an entire week.

Then when they looked at the incidence of acute atrial fibrillation, heart attack, heart failure, or stroke, what they noticed is that there were similar declines in each of those, regardless of whether someone was a weekend warrior or whether they spread the activity out through an entire week. By the way, all of those were substantially decreased by 20% to 40% compared to those people that were inactive.

Elizabeth: Okay. This is all moving into no excuses because the other thing that we, of course, have noticed about physical activity is that even if all you do is get up and move for 5 minutes at a time, 6 times during the day, that that also results in significant benefits.

Rick: Absolutely. I mean, if you just even do a half or a third of the activity that’s recommended, you can still decrease these outcomes by 30% or 40%. Doing something is more important than doing nothing. It doesn’t have to be done every day of the week, so people can find the rhythm that best suits them. There are some individuals that want to do it every day of the week because it maintains that consistency, it’s easier for them to do it, and they have the time. But individuals like me, I can concentrate on 1 or 2 days a week and still get the same outcome. That’s great news.

Elizabeth: Yeah. For you, that’s, of course, great news. Finally, let’s turn to the journal Pediatrics, and this is a look at IQ after pediatric concussion. We’ve been doing an awful lot of talking about concussion and about its deleterious impacts.

In this study, they had 866 children between the ages of 8 and almost 17 years of age, and they were recruited from two prospective cohort studies from emergency departments both in the United States and in Canada. They were recruited sometime in the 48 hours after sustaining their concussion or they had a control group that had orthopedic injury.

In the United States, they administered IQ tests and performance validity testing post-acutely 3 to 18 days after their injury, or 3 months post-injury in Canada. They took a look at IQ scores and they examined them with three different statistical approaches. What they found, and this should make everybody feel really happy, is that there were no clinically meaningful differences in IQ scores after pediatric concussion.

Rick: This is a hard study to do. Because if you want to do it in the most rigorous way, you do an IQ test on all the kids before they have their concussion and an IQ test on them afterwards. But then you’ve got to know which kids are going to have a concussion. The investigators, realizing that couldn’t be done, they compared kids that had a concussion versus kids that also had sports injuries, orthopedic injuries, but without a concussion. As you mentioned, there was no meaningful difference in IQ either short term — as within days — or months afterwards.

Now, we’re not advocating for a concussion, but it is a little reassuring to know that, at least in these cohort studies, that there is not a meaningful difference in IQ for kids that have concussions. This is considered mild, traumatic brain injury, not moderate or severe, because we know that can affect both neurodevelopment and IQ. For these mild traumatic brain injuries, it doesn’t appear to significantly affect IQ.

Elizabeth: Right. Now, I would also note that just today there was a study that was undertaken by the British Football Association, aka soccer, taking a look at repeatedly “heading” a ball and whether that ultimately impacted. They did find that there was a problem. Once again, back to a single, mild concussion may not be problematic in the long term, but repeated injury for sure is something that we really need to pay attention to.

Rick: In the sports world, that chronic encephalopathy can develop with repetitive, severe head injuries.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.