S4 E15: Donanemab & Alzheimer's Disease; Diet Against Dementia; Weekend Exercise; Opioids & Acute Back Pain

Welcome to the Hot Topics podcast from NB Medical with Dr Neal Tucker.  School's out for summer but general practice never stops. This week we look at the medical news story of the week: donanemab for Alzheimer's disease - can this monoclonal antibody revolutionise dementia care?

Also in research, prevention is better than a cure, so can a Mediterranean-DASH diet keep cognitive decline at bay? For you weekend warriors out there, is cramming exercise into the weekend as good as exercising throughout the week. A new paper in JAMA answers this question. And is there ANY role for opioids in acute back pain? A new Australian study goes strong to see if there is benefit with this common problem.

Don't forget to check out all our upcoming courses including the new Hot Topics course in September and much more on www.nbmedical.com.

References

JAMA Donanemab
NEJM MIND diet for dementia prevention
JAMA Weekend warriors and CVD risk
Lancet Opioids for Low back and neck pain

www.nbmedical.com/podcast

Transcript

Speaker 1: 0:01

School's out for the summer. Baga. It's Friday, the 21st of July. This is the Hot Topics podcast. Welcome to the Hot Topics podcast from MB Medical. It's Neil Tucker here to take you through the next 20 minutes or so on what's been going on in general practice and the world of research in the last few weeks. It is now officially the summer holidays.

Speaker 1: 0:36

This will strike fear into those of you with children and you will either have been desperately scrabbling around to try and find some childcare be that friends, be that family, be that some kind of holiday club to put your kids in so that you can still keep going to work, or you've already fought to the death with your colleagues. Presumably you're the winner if you're listening to this, so that you can have the privilege of paying grossly extorted fees for holiday in the summer break. What I do like about the summer is that for most practices things seem to get a bit easier, so the demand goes down. It's not crazy like it was over winter. I don't know if it's just the sunshine, if people don't get so ill, they just don't have as many infections, or if maybe they've just stopped bothering coming to us. I don't know. Whatever it is, it doesn't feel like the chaos that was going on at the start of the year. So in this research today, we're going to have a think about this new dementia drug that hit the headlines this week. We're going to also have a think about whether diet can modify your chance of developing dementia. We're going to have a look at whether exercising just at the weekend can help produce your cardiovascular risk. And we're going to have a look at an interesting paper Interesting, because it's slightly baffling to me why they did it.

Speaker 1: 1:51

This is a paper that published in the Lancet this morning on the use of opioids for acute low back pain. Not just codeine, not just tramadol, but a good dose of oxycodone. Is this just what patients need when their back starts to hurt? In news, lots of doctors have been striking in England, but of course not in general practice, not least because the GP committee of the BMA seems to be in utter chaos right now. Meanwhile, the government have graciously offered a 6% below inflation pay increase for salaried staff in GP practices and they will increase the funding to practices to accommodate that. Well, probably not all of that, not extra pension contributions and national insurance and all those kind of things, but you know some of it. Partners continue to get a raw deal. Retention woes continue when we go round and round in circles. If we were on national TV, this would be about the time I'd bring out a dog on a surfboard to make everyone feel happier, but instead we're going to have a look at some research.

Speaker 1: 2:52

The big news story this week was, of course, about Dunonimab, a monoclonal antibody that clears amyloid plaques from the brain and has been hailed as a turning point in the fight against dementia. This study was published in JAMA this week and had no less than four accompanying editorials. Will this drug change how we manage dementia? Probably not. Why not? Well, there's a whole range of issues. It's got debatable. Real world benefit it's way too expensive. It requires specialist radiological investigations to determine who should get the treatment in the first place and then monitoring them once they're on it, of which we have limited access to in the UK. It's associated with serious adverse events for some patients.

Speaker 1: 3:44

The final current research only examined a very narrow group of patients, with 91.5% of participants being white. So what did they actually do in the trial? So this was a randomized controlled trial of over 1,700 participants with early symptomatic Alzheimer's disease, an amyloid and tau pathology. I had to look the latter one up. So tau pathology correlates with functional deficits. In people with Alzheimer's, it's another protein, like amyloid, that gets deposited around the brain. So first up, patients need to have that identified, and to do that you need to do a PET scan.

Speaker 1: 4:24

Once that was confirmed, half of them were randomized to receive IV Donanumab every four weeks for up to 76 weeks, and the other half received placebo injections. The primary outcome was change in integrated Alzheimer's disease rating scale, which is a validated tool looking at cognition and daily function. There was a whole bunch of other endpoints that they looked at, including re-scanning people to see what was actually going on with those amyloid and tau plaques. Good news, then, for the manufacturer that this drug is very good at clearing amyloid plaques. 80% of the treatment group had them cleared.

Speaker 1: 5:01

Bad news, though, that the clinically important stuff like cognition and daily function all continued to get worse, albeit at a slightly slower rate, in the treatment group. One of the editorials comments that this slightly less worsening is small when looked at in absolute values, although it does go on to acknowledge that slowing progression by a quarter to half a year, as seen with this medication, to allow someone to remain in a group where they may be classed as having mild cognitive impairment or mild stage dementia, rather than progressing on to more moderate dementia and having more significant impact on daily living. Well, that may be meaningful for some. What's the big barrier here? Well, no one really knows what the cost of this medication is and, of course, more and more we're seeing expensive drugs be negotiated in price between drug companies and governments or health services. But the company's own stated price for cost effectiveness analysis that some researchers had been doing was $28,000 per year. It seems pretty unlikely that at this price, nice is ever going to give it a seal of approval.

Speaker 1: 6:13

I almost forgot to mention drug related complications, and this is also important for this treatment group and we're also seen in similar drugs such as Lacanamab. One in four people developed brain edema or effusions Definitely a drug effect, because only 2% in the placebo group showed the same. One in three in the treatment group had evidence of brain hemorrhage, compared with about one in seven or eight in the placebo group. Difficult to know how clinically important those figures are, but it is worth noting that there were three deaths in the treatment group that were attributed to the drug itself, compared with one in the placebo group. So this is a very expensive drug with potentially significant risks and minimal clinical benefit.

Speaker 1: 7:02

Are we going to see Denonimab in the UK anytime soon? I don't know. I think so. Sorry, everyone, that's the best I've got today. Perhaps, instead of relying on very expensive medications to help with dementia, we could just think about lifestyle measures. What about improving our diet for preventing cognitive decline in older people? Now there has been some observational data suggesting that a mind diet, so that's a combination of the Mediterranean and the DASH diet. So DASH stands for dietary approaches to stop hypertension. These diets focus on reducing red meat consumption, increasing green leafy vegetables, about all vegetable consumption, healthy fruits, nuts, olive oil, whole grains, fish, beans, that kind of thing. It's been speculated that they may offer protective benefits against cognitive decline, but this is the first randomized, controlled trial to look at the mind diet for prevention of cognitive decline in older people. This was published in the New England Journal of Medicine last week.

Speaker 1: 8:12

This was a study done in America. So they recruited older adults without cognitive impairment but with a family history of dementia. They needed to be overweight, so they had a body mass index of greater than 25% because they were going to be put on a diet and then they had to have a suboptimal diet as well. They managed to recruit 600 people. 300 went into the mind diet group and 300 went into the control diet group. So both of them got dietary counseling. Obviously, the mind diet group focused on all those good foods and in the control group they continued to have their normal diet, but they were counted on things like calorie tracking, portion control, behavioral strategies to lose weight. So they were meant to be in a bit of a calorie deficit to try and help get that weight down. At three years, which was the end of the trial, there was good news and the good news was that actually both groups got a little bit better. Their global cognitive scores improved. It wasn't by a huge amount, but they got a little bit better. The bad news for anyone pinning their hopes on the mind diet is that it wasn't any better than the control group. This doesn't mean there is no role for the Mediterranean or for the diet. They still could have benefited in people for reducing their cardiovascular risk profile. But perhaps the key message coming out of this study is simply that if we try and be a bit more healthy with our diet with our lifestyle in whatever way, then that might lower our risk of cognitive issues in the future. This brings us neatly on to our third study, which also has a lifestyle theme and the title accelerometer derived weekend warrior, physical activity and incident cardiovascular disease.

Speaker 1: 10:01

I'm sure many of you and many of our patients would like to be doing more exercise, but life gets in the way. Whether it's work, family, whatever, it's just too busy. Fitting an injury in the week is very, very difficult. So what if you're someone like me who enjoys putting on lycra at the weekend? Just to clarify, that is to facilitate exercise, it's not just to scare the children. Is exercising at the weekend as beneficial as being able to do regular exercise throughout the week? This was published in JAMA, but actually it's based on UK data and it's quite phenomenal. This is from the UK Biobank and they gave 90,000 people accelerometers to collect data on activity throughout the day.

Speaker 1: 10:48

The researchers then stratified people into three groups so you could be an active weekend warrior. So your total weekly exercise time was over 150 minutes and over half of that had to be within the one to two days of the weekend. You could have been an active, regular exerciser, so you've done more than 150 minutes, but that spread more throughout the week, not just at the weekend, or you were in the inactive group that did less than 150 minutes of exercise in that week. The average age of participants was 62 years. 56% of them were women and, amazingly, a vast majority actually fulfilled the criteria for being active 42% were in the active weekend warrior group, 24 were in the active regular group and 34% were in the inactive group. Good news, then, for weekend warriors, because whether you did it all at the weekend or you did it throughout the week, the improvements that you saw were very similar and markedly better than the inactive group. To give you a few examples compared with the inactive group, the active group had a reduction in MIs of around 25 to 35 percent, a reduction in heart failure of around 35 to 40 percent, reduction in stroke of around 20 percent.

Speaker 1: 12:14

The caveat is that this is observational data, so we can only show an association between physical activity, whether at the weekend or throughout the week, with lower risk of cardiovascular outcomes. We can't show a causal response. You could argue that this active group is also more likely to have a better diet, or maybe be in a higher socioeconomic group or live in a nicer area, be less exposed to air pollution and so forth. Regardless, for me, what this study shows is that we can be very positive with our patients. If they want to do some exercise, we can say to them it doesn't matter if you can only do it at the weekend, it's going to be helpful. Go and enjoy yourself with the knowledge that it's also going to be helping your cardiovascular health.

Speaker 1: 12:58

Our last study of the day is one looking at a very common problem, and this is acute low back pain and acute neck pain. We know this can be really unpleasant for our patients. We also know that treating this can be very, very challenging. The latest nice guidelines on managing low back pain suggest that we could consider all all steroids for low back pain. Consider weak opioids where that's contraindicated or it's been ineffective. Don't offer paracetamol and don't routinely offer opioids for managing acute low back pain, although the implication from that is that we may non-routinely consider using opioids in that situation. That's the starting point for this study.

Speaker 1: 13:43

This was a triple-blinded, placebo controlled, randomized trial conducted in primary care and emergency departments in Sydney, australia. Participants were adults with at least moderate pain in their low back or in their neck, or in both. They were then randomized to either the control group, which was guideline recommended care plus a placebo for up to six weeks, or the active group, where they gave guideline recommended care and, rather sportingly, 20 milligrams of oxycodone per day in a tablet with both oxycodone and naloxone in it. This seemed a bit sporting to me, but, as the authors point out, as high as two thirds of people in Australia receive an opioid as first line treatment when presenting for care with low back pain or neck pain. I've no idea what the figures are like in the UK for this. I'd like to think they're much lower, but the reality is there's probably lots of situations where we give out opioids because we just want to try and help people, even when sometimes we know that this won't help people. It came to pass that this is exactly what happened with oxycodone as well. When they looked at pain scores, quality of life, in fact, any metric that they looked at over the course of the study, they found that they were no different in the group with oxycodone compared with those receiving the placebo. This wasn't just at week six. It was at week two and four and six and 12 and 24 and 52. The bottom line is opioids don't help. The authors concluded that opioids should not be recommended for acute, non-specific low back pain or neck pain. This would be a great time for me to go, but here's another study that shows this might help, but I don't have one.

Speaker 1: 15:33

Sorry, everyone, when it comes to back pain, we're on our own. Okay, everyone, thank you. That is it for the research and it for the podcast. Today. Nb takes a little bit of hiatus over the summer. Do check out the website so that you can get yourself prepped up for the whole range of new webinars that we've got coming up. In September and beyond. We will, of course, have a new Hot Topics course coming out at that point, but also we've got our new Dermatology course, women's Health, diabetes course loads more as well. So do check out the website. Probably we'll have one more podcast before then over the next few weeks, but I hope that you have a very nice summer. I hope that maybe you get to go on holiday, I hope maybe the sun comes back and, if nothing else, I hope you get to pull on some Lycra this weekend. Take care, bye-bye.