Guinea pigs in the service of science

"It's changed our lives," Imma Santiago Die affirms with conviction and a genuine smile. "Not just mine, but everyone who's participated. We're not the same as before," she insists, giving her sister Carme a knowing look, who nods in agreement. "Now we take care of our diet, we exercise, do cognitive stimulation, and go for walks and do activities together. In fact, we're meeting up for lunch today," she explains.

Five years ago, when Imma was 67, she learned that the Hospital del Mar was recruiting volunteers for a dementia prevention study. She had just participated in another study by the Pasqual Maragall Foundation and was very satisfied with the results, so she not only signed up herself, but also convinced her sister Carme to join. "They gathered the eleven volunteers in Barceloneta, and we left feeling a bit scared. They gave us a dossier and various materials and explained everything we would have to do," explains Imma, who recalls that they ended up "speechless, because it required so much dedication." "It was exactly like having a job!" she exclaims. These sisters even say that "one man quit shortly after because he couldn't sustain such a commitment."

The study that Imma and Carme signed up for was PENSA, a clinical trial conducted jointly by the Hospital del Mar Research Institute (HMRIB) and the BetaBrain Research Center of the Pasqual Maragall Foundation. It aimed to evaluate whether an intervention targeting a higher probability of developing dementia could prevent its onset. In fact, the volunteers had to be carriers of the APOE4 gene, which increases the risk of developing the neurodegenerative disease up to five times.

Of the 1,500 people who applied, 129 were recruited. They were healthy individuals, aged between 60 and 80, who were closely monitored between November 2019 and March 2023. "It is the only study of its kind in the world," said Rafael de la Torre of HMRIB. Previously, the research team had already studied...Impact of the Mediterranean diet on cognition and had collaborated on a project at the Centre for Genomic Regulation, led by neuroscientist Mara Dierssen, to evaluate the effect of a molecule in green tea, EGCG, to improve cognition in people with Down syndrome. "Then we wondered if all those results could be applicable to people at risk of developing dementia," explains De la Torre, a professor at Pompeu Fabra University (UPF).

The day we met with Imma and Carme, the team of scientists had gathered the study participants to explain the results they had obtained after monitoring them for fifteen months: they found that participants who completed the entire study program—diet, physical activity, and personal training—experienced up to a 4-point improvement in cognition, a reduction of approximately 25%. "We required them to go to the gym with a trainer and participate in daily psychostimulation sessions. They had to follow a personalized diet and take part in group activities, such as outings to the theater, concerts, cooking classes...," explains De la Torre. "Some complained that they didn't have time left to spend with their grandchildren." They also received training on cognitive decline and Alzheimer's disease and the role of lifestyle in these conditions. "We wanted to empower the volunteers: to teach them the science behind every piece of advice we gave them," says Laura Forcano, a psychologist at Hospital del Mar and HMRIB. Perhaps participating was demanding, but for Forcano, in the end, it was a win-win:"We were able to extract the data we needed to carry out the study, and the volunteers adopted healthy lifestyle habits that benefited them," he points out.

Contribute to the common good

Neurodegenerative diseases, like Alzheimer's, They are the leading cause of disability worldwide, ahead of cancer and cardiovascular disease combined. Current estimates indicate that within ten years, one in three people between the ages of 40 and 65 will receive a diagnosis impacting their mental and brain health, which in turn will affect their quality of life. Faced with this global challenge, understanding what causes brain disease is crucial.

And that is precisely what this study aims to achieve. the Barcelona Brain Health initiative (BBHI)Led by the Guttmann Institute in collaboration with the University of Barcelona, ​​this type of study requires statistical power: large amounts of data from a diverse sample of patients over a long period. Only then can conclusions be drawn. In this regard, the BBHI has been following more than 6,000 healthy people over 40 years of age, residing in Spain, for eight years to study the biological impact that modifiable lifestyle habits have on brain health.

“We wanted to learn and understand how to maintain brain health over time,” says Javier Solana, research director at the Guttmann Institute. This, he explains, is achieved by “studying the brain before disease appears and looking for associations between a person’s lifestyle and the pathology they may develop in the future, with the aim of finding preventative measures.” The Guttmann Institute only needed two days to recruit the 6,000 volunteers it required. “Three types of profiles signed up: people who suspected cognitive decline but didn’t have a diagnosis; people with a family member with Alzheimer’s; and, finally, healthy, highly motivated people who altruistically dedicated their time to participating in the study. They are the ones who fascinate me the most,” Solana explains. Among the people in the third group is Isabel Moya, who was 45 years old when she signed up. "I had the feeling that there was a lot of research focused on the body, on extending youth, but little on the brain," he recalls. At first, participation was demanding. Guttmann has quantified the effort and generosity of the 6,000 volunteers: they answered 105,000 online questionnaires, yielding 14 million responses about lifestyle habits, medical history, and environmental, psychological, and social factors, as well as health complaints. In addition, 1,000 people in the cohort underwent two rounds of in-person medical tests, such as blood work, brain scans, and electroencephalograms, among others. The equivalent, in total, of 946 days. There are even volunteers who come from as far away as the Canary Islands, covering their own airfare, accommodation, and meals. "Their commitment to the research is incredible," Solana acknowledges, speechless. The majority of the volunteers, again, are women. "It has been very enriching. The project helps you get to know yourself better and, at the same time, you contribute to science.", Isabel says, joking: "If they ever discover a formula to keep the brain young, I hope to be one of the first to try it."

Participation in all phases

For some years now, at least in Europe, volunteers have not only participated in the study itself as guinea pigs, but also in its design. In the case of the BBHI, Solana explains, they selected a small group of volunteers to work on aspects of the research, the website interface, and the length of the questionnaires. Another innovative aspect of recent years is the increasing consideration given to gender and sex perspectives. The European Commission also requires this in all the projects it funds. Solana cites menopause as an example: "At the beginning, we didn't collect data on it, and three years later we started doing so. Now we consider this stage of a woman's life as a risk factor for cognitive decline and dementia. We don't have results yet, but it certainly has an impact," she points out.

The return to society

"I always have a yes for this home"They've cared for me and cured me, I trust them 100%. So, if they ask me for a sample and I can contribute to other patients getting better and not having to go through what I did, what's it to me?" says Tanit Tubau, a 36-year-old who exudes enthusiasm, referring to the Hospital Clínic in Barcelona.

Tanit has suffered from Crohn's disease since she was 9 years old, version "black hoof"," as he humorously refers to this inflammatory gastrointestinal disease. He has undergone sixteen surgeries, recovered from a coma, had a bone marrow transplant, and tried all sorts of treatments. "People think Crohn's is just a stomach ache, when it's an autoimmune disease, like his Crohn, She is also a volunteer black hoofIn addition to providing blood and tissue samples whenever requested, she has written a book and organizes fundraising events for research, and is very active on social media raising awareness about the disease.

The samples from Tanit, and also those from Isabel, a woman who began suffering from ulcerative colitis at age 60, are a precious treasure for conducting studies on inflammatory bowel disease. "Animal models are useful for investigating certain mechanisms, but ultimately we have to look at what happens in humans. Research in theIDIBAPS, the biomedical research center linked to the Hospital Clínic Barcelona, "It's 100% dependent on the samples that patients altruistically give us," says Azucena Salas, head of the IDIBAPS research group on inflammatory bowel disease.

The samples that patients "generously" give to the center go to the tissue biobank. Aina Rodríguez, head of scientific platforms at IDIBAPS, listens attentively as she explains how this repository works. "What you're doing is incredibly generous, and that's why we want to give back a little with these visits, also by going to patient associations to raise awareness, giving talks in schools... It's our way of trying to contribute to giving back."

Tanit stares in wonder at all the tanks. patients, and he liked seeing where the parts of his body he had had to part with were stored: fragments of his colon, his rectum... "Since they're stored here, it's as if I haven't completely gotten rid of them. They hurt me, but now they're useful for other patients and can help research. And that's worth any effort I have to make."