This is the Guardian. Alzheimer's disease is one of the most devastating diagnoses to receive. Which is why, in 2022, when a trial of a new drug found its slowed cognitive decline in patients in early stages of the disease, there was genuine real excitement. The drug is called Lecana Mab and it's not a cure, but it does delay cognitive decline. This is big news because the more Alzheimer's progresses, the more patients lose their independence. They're memory and so many aspects of living that are so precious to them. Now, a review has looked at whether they really do make a difference. When Ian and I get into the studio together to discuss the latest scientific research, there's never a lack of interesting topics to get into. What we actually end up chinwacking about, the lunch offering in the canteen, train delays and what we got up to at the weekend. And a new study offers a clue as to why we enjoy a little gab. But the subject you can knatter to any Brit about is, of course, the weather. And it looks like our favourite kind of small talk is about to be supercharged, as experts say a super El Nino is brewing. But is the world ready for what it will bring? From the Guardian, I'm Madeline Finley and this is Science Weekly. Ian, a few years ago, we reported on an exciting new treatment for Alzheimer's. Drugs that were hailed as bringing in a new ear-refer people with their disease to slow its progression. It all felt really hopeful, but at the same time there were these uncertainties around how effective the treatments were and their side effects. Now, a big review has come out that's looked into these questions a little bit more. But first of all, what do we think actually causes Alzheimer's disease and how are these drugs then thought to work? Well, what causes Alzheimer's disease is probably one of the biggest questions in Alzheimer's disease research at the moment, right? When you look at the brains of people with Alzheimer's disease, the hallmarks that people always talk about are clumps of amyloid beta protein and they form in between neurons in the brain. But you also see something called tau tangles. These are another type of protein that that tangled up inside neurons. And it's the tau tangles that seem to be most closely linked to cognitive decline. But the amyloid may be important for initiating the disease. And so what these drugs are doing is they are looking to take out the amyloid from the brain in the hope that if you get rid of that, that is actually a major cause of the disease that you see. But that really is still not very well understood. So the antibodies are helping to clear out this amyloid. I remember the initial excitement around the potential of this. So what led to the review of the drugs? What were they actually trying to find out? Well, yeah, these drugs were received with huge excitement because the data was suggesting that they were the first drugs to interfere with the progression of the disease. First of all, it's worth saying that two of the drugs that were mentioned in this review are Lecannamaab and Denanamaab. And they have been approved by medicines regulators in the US, in Europe, in the UK and other countries. But certainly in the UK, the body that we have called NICE, which stands for the National Institute for Health and Care Excellence, they decide on which drugs make sense for the NHS to provide. And they've decided that at the moment it doesn't make sense to offer those drugs because they just don't see a good enough benefit. But the point of this Cochrane review was really to pull together and analyse all of the randomised controlled trial data and look at the outcomes for people with mild cognitive impairment or mild dementia, the people who would be getting these drugs right. They were looking at both the benefits and the harms in nine different amyloid beta targeting antibody drugs. And for the review, they pulled together 17 studies with a combined total number of participants of just over 20,000. Yes, because I can remember when you were first reporting on the drugs and there was this sort of concern around the seriousness of the side effects. So what did the review find? So the review found that there was no question that these drugs can reduce the amount of amyloid in the brain, which is what they're designed to do. But there was serious doubt about how clinically meaningful the impact of that on the disease was. They had mixed results across different randomised control trials for different drugs, but they found little to no difference in the severity of people's symptoms when they took these drugs and no difference in the decline of memory and thinking. They did fly one study that found a small improvement in people's ability to do complicated tasks like transport or managing finances. So for the benefits, really they found that these drugs were clinically meaningless. They also looked at the side effects and the harms, which we know about from the trials when they first came out. And certainly in the groups taking those drugs, there was a small increase in the risk of brain swelling and microbleeds on the brain. And many of those were asymptomatic. They weren't causing any problems. But some did. And they were considered a potentially life threatening. This is such an interesting result for this review to conclude. What does it mean for this kind of therapy for Alzheimer's and actually for our understanding of the disease itself? The fact that the drugs were able to clear the amyloid, but that didn't have a clinically meaningful effect suggests that there is this question around the theory and what role the plaques are playing in the disease. So what should we take from this? I should say that the reviewers themselves say that there are limitations in the work that they've done and particularly this is really driven by the studies that they were looking at. And the length of those was between 18 and 24 months. That is a substantial amount of time to give someone a treatment for, but you may see more benefits, you may see more risks. If people are on those drugs for longer, that is something that we will find out as these trials do carry on. Cockrore reviews are held up as the gold standard for assessing whether drugs, for example, do or don't work. But the criticisms are quite strong. And some scientists have been saying, look, what they've done is they pulled data from clinical trials of drugs that simply haven't worked. Some of the very early drugs that were targeting amyloid. And they've pulled those together with drugs like Lecana Mab and Denanama, which have shown a modest effect. So if you do that, you really obscure any kind of benefits from those drugs, and that you make it look like all of them fail. And researchers are saying that there is actually still some cautious optimism that these drugs will work, perhaps in people who are particularly at risk because of genetics to Alzheimer's disease, maybe getting into them early, or maybe that these drugs will work if given enough time in patients. But in the end, this review was pretty damning. I'll quote from the review and it says, the current results make clear that successfully removing amyloid from the brain probably does not result in a clinically meaningful effect on cognitive decline in patients with mild cognitive impairment or early dementia due to AD Alzheimer's disease. New mechanisms of action for treatment of AD other than aiming for amyloid removal should be explored. So what they're saying is that you need to go back to the drawing board and find drugs that are tackling another part of this disease. I think really my taking from this is that yes, amyloid is part of the story, but it's not at least from the evidence at the moment the best target for trying to improve people without Alzheimer's disease that you need to find something which is actually preventing the damage and this does not seem to be it. Maddie experts have sounded the alarm that we may be heading towards a super el Niño, an extreme weather events and record temperatures. Remind us first for what is el Niño. An el Niño is part of a climate phenomenon known as the el Niño Southern Oscillation or the endso. The other phases you can have a neutral phase, but then the other main one is called a lanninia and they each tend to last around nine months to a year and they begin to develop in the spring in the northern hemisphere. Now all of this centers around the winds and temperatures in the Pacific. It's not a regular cycle but there's an approximate two to seven year period where there's a fluctuation between an el Niño neutral lanninia. It is a quite a complicated picture, but in essence during a lanninia you'll see cooler temperatures and more precipitation, downpours, storms in Australia and southeast Asia as well as in the north of [BLANK_AUDIO]
South America, and El Nino is the opposite, so that's hot temperatures much drier in the regions that I mentioned, and both mean worse and extreme weather events. So in an El Nino, which we're expecting to see later this year, you're going to have more and worse droughts, wildfires, heat waves again across Australia, India and the Amazon. Although you could as well see heavy rains in southern parts of the US and severe storms elsewhere. So what are the signs that a super El Nino could emerge this summer? So just to say a super El Nino is just one that is much stronger than might be typical, and to work out whether an El Nino is coming, experts monitor the sea surface temperatures and they use satellites and boys out in the Pacific Ocean, and anything above 0.5 of the average sea surface temperature indicates that an El Nino is probably coming, and a super El Nino you would see the temperature rising to at least two degrees Celsius higher. There are a few things that make predicting whether you're going to have an El Nino or a La Nino quite challenging. The first is that spring is a natural time of transition, so the temperatures are changing. The second is that actually we're coming out of a La Nino now where you would see lower surface temperatures, typically. And the third is that obviously the oceans are getting a lot warmer due to human induced rising global temperatures. So this might actually make an El Nino look stronger than it ends up being. Scientists from the National Oceanic and Atmospheric Administration have now said that there's around an 80% likelihood that an El Nino is going to develop later this year, and there's a one in four chance it's going to be a very, very strong one, and perhaps even the strongest in at least a decade. As you said, the ocean is trapping an awful lot of heat. Do we know if this impacts on El Nino's and La Nino's? And remember we had an El Nino in 2023-24, and that was like the fifth most powerful in recorded history. Are they getting worse and more frequent? This is a really interesting question, and scientists aren't necessarily in agreement on the answer. There was a recent study that found that El Nino's and La Nino's have been getting more frequent and intense since the 1960s. So that's really when you're going to see those ocean temperatures massively ramp up. But another suggested that events have been increasing in duration and frequency over the past 7,000 years. And the answer was probably going on for tens of thousands if not millions of years, and it swings over the course of decades. So it's actually really, really hard to tell if this is something you'd see without rising ocean temperatures. What I would say is that the climate crisis is already bringing worsening extreme weather events. According to the World Meteorological Organization, the last 11 years were the world's warmest on record, and just to hit this home last year was one of the three warmest since records began, and we were in a Lanemia, you know, a year when it's supposed to be cooler. So the last thing that you want is a great big whack from an El Nino on top of all the other problems that we already have from the climate crisis. You know, the more our earth heats up and the more feedback loops we get into, the closer that we're getting to all these tipping points. But unfortunately, Ian, it looks like this is what we're about to get. Starting up, while having a natter about the weather really will be less dull than you think. In every time we record together, we have a little chat about our days. You know, I always ask you what you're working on. We talk about the snacks that we've had, what we're listening to, what podcasts we're into, all of that stuff. And so I wondered what your capacity is for small talk. Do you dread walking into the studio? Or are you always ready to discuss the weather with me? I worry that I have an endless appetite for small talk. I really like talking to people, whether I know them or not, and I'm not saying I go up to people out the blue and start talking to them because that would be irritating. But I can't honestly remember the last time I had a boring conversation. And I really mean that. Wow, well, that's surprising, Ian, because the last time I ran, I was talking to you about a banana. But apparently, even that wasn't boring. So let's talk about this study that you've reported on this week because that kind of ties in to that idea that even me talking about a banana isn't boring. This was published in the Journal of Personality and Social Psychology, and it boldly stated that conversations about boring topics are more interesting than we think. Tell me about it. What was the premise of the study? Well, the researcher was telling me, she said, look, I'm one of these people who will avoid conversations with certain people, will not want to engage. It might be draining. It might be boring. And they want it to know, well, why is this? Because there's actually a lot of evidence that shows that having conversations with people is really good for your wellbeing and so on. And so yeah, they wanted to know, why do we avoid small talk? And why do we so often expect conversations to be dull or really tedious and draining? And so what did they do? How did they test this out? So they recruited about 1800 people, and they ran a series of experiments during which these people were either given lists of topics deemed to be boring, or they gave examples themselves of topics they would find boring. And these people were put into conversations either in person or online with people they knew, with friends or with total strangers. And before the conversations, they were told to say, how interesting do you think you're going to find this conversation? And consistently across the board, even when both people going into the conversation agreed that a topic was going to be dull, people consistently found the conversations more enjoyable than they expected. And just give me a flavour of some of the topics that the participants deemed would be boring. For that the researchers mentioned to me that people generally thought, well, it lead to a pretty dull conversation where the stock market, onions, Pokemon and vegan diets. And you can see where the people are coming from and that they rated those things as being pretty dull, but there was a long list. I'm so impressed that people are able to have a whole conversation about onions, and I was so really joy it. So what does this say about the power of communicating and connecting with other people? I remember it was during the pandemic actually that we did an episode about the value in talking to strangers, I guess it was when we weren't able to. And the fact that it can be so good for us. What I thought was really interesting from this study was that the researchers conclude that what people are doing when they are imagining how conversation might go and often deciding not to get in there is that they're making that judgement based on what they call the sort of static components of a conversation. So if you think you're going to go into a conversation about a topic that you find dull, then your judging how much you will enjoy the conversation based on the topic. But what seems to actually predict how enjoyable a conversation is is the dynamic component of the conversations. Simply this connection with another person, maybe you're being heard, you're having this to and fro with someone else and those dynamic things in of themselves are actually really enjoyable and give us a nice boost regardless of whether you're talking about onions or Pokemon or something like that. And the researchers were saying maybe we need to just rethink what we're going to get from a conversation as before we judge it. You're not always in the mood to have these kind of small talk conversations, but for those people who really struggle with the idea of sparking up a conversation in a taxi or at the hairdressers or in the sauna, really they've got to take the bull by the horns and just go for it. I think that's right. I've never regretted the sort of random conversations I've had through the day and Lord knows there are enough of them. But one thing the researchers pointed out was look, don't take this too far and that it doesn't mean that you should be seeking out boring conversations or wherever you go because there probably is a sort of diminishing return. And I think what she phrased it was this probably doesn't scale indefinitely. So don't bring up bananas to everyone I meet. Note it. Thanks to Ian. You can find all our reporting on these stories at theguardian.com. And if you'd like to tell us what your favorite or. least favourite small talk topics are, we'd love to hear from you. Or let us know what science you'd like to hear about so you always have an interesting fact on hand. email in on
[email protected] That's it for today. This episode was produced by Ellie Sands. It was sound designed by Joel Cox and the executive producer is Ellie Beary. We'll be back on Tuesday. See you then. This is The Guardian.
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