Silence, the Shipwreck of the Mind

CESAR CRUZ REQUEJO

19 March 2025

Read the original version here.

More than 900,000 people suffer from Alzheimer's in Spain. Currently, there is no cure. It is a disease that erases memories and blurs identities. Alejandro, whose father was diagnosed in an advanced stage, shares his experience with family members and experts from medical foundations and hospitals in Madrid and Barcelona.

I - Dying Twice

“It must be the age.” That sentence, laced with hints of ageism, was what doctors in the 1990s cited as a possible cause of progressive cognitive decline. “I call it a double death for the simple fact that the mind dies, you’re confined to a chair, and later the body dies,” is the case of Alejandro, a young caregiver whose father died overnight in 2016, after a late diagnosis about thirty years earlier.

How does Alzheimer’s disease (AD) affect the brain? What does it mean to live with this neurodegeneration? Alejandro captures the experience of this process both literally and metaphorically through Greek legends and mythology in his book, Dying Twice (Morir dos veces). On each page, he delves into the personal experience of a child who comes of age looking after his father. He decides to take care of him in his living room with the help of his sister and mother. This way, he relives the fleeting wisdom of an absent parent.

On a warm afternoon in Peru, Alejandro shares the reason for his book. From his literary tour, the Barcelona native explains how the disease varies greatly depending on the follow-up and treatment received. Today, there are many associations dedicated to helping affected families with therapy or support groups. “It would also be good to look at the financial support each family receives,” Alejandro points out. “There is a big difference in the treatment of those who suffer from Alzheimer’s in places with greater access.”

With this bad guy, as the Royal Spanish Academy or national dictionary puts it [mal in Spanish], you never know how quickly the person will forget. Suddenly, you rely on the hope that they will recognize you, but the thought rapidly dissipates. “My father was alive when the book was already finished.” Precisely at the end of Chapter 29, ‘The Second Death,’ “he goes to bed that night in 2016, and the next morning, my mother finds him lifeless.”

His father lived mostly on his couch, where he only moved to beam at them. The man wore that innocent smile that doesn’t truly process his surroundings with the awareness of a person with a healthy brain. Even so, he witnesses his descendants, who give every minute, every second of effort to improve his vitality. Salvador’s case in Dying Twice manages to identify the reality of this illness in an environment where euthanasia, intensive care, and third-party services are refused for the family to look after him themselves.

“Alzheimer’s starts in silence”

Similarly, Pedro sees it through a caregiver lens. A 70-year-old, whose wife has suffered from Alzheimer’s for about twenty years, began to notice the symptoms as time went on. These were progressive and increased. Contacting him via WhatsApp and email, he claims that the woman he loves did not have a good night; he would rather not talk.

“Alzheimer’s starts in silence,” says Alejandro. In any case, “we are devastated by the speed at which autonomous thought vanishes in the brain and how fast they forget the face and identity of family members or acquaintances.” Pedro’s partner has become dependent.

Days pass, brain atrophy sets in, and the cortex thins, affecting areas responsible for thinking, planning, and memory. Also, the hippocampus shrinks, affecting the formation of new memories. This results in loss of synapses and neurons.

According to science, synapses are the communication between neurons. Therefore, cognitive function declines, and neurons progressively die. Language becomes instantly burdened by the struggle to find words and to understand them. This hinders self-judgment and is an early symptom. Spatial orientation worsens when it becomes tricky to recognize places or loved ones, and it is easy to get lost on familiar routes.

What are the risk factors? Alzheimer’s disease is influenced by risk factors divided into non-modifiable ones—such as age, genetics, and even, according to some evidence, being born a woman—and those that can be modified. Nationally, 32 percent of women suffer from some type of dementia. Age is the main factor since the risk increases especially after age 65, but many people maintain their cognitive function for years. It should be noted that younger people may also develop the disease, which means that aging increases the risk, but it does not mean that everyone will experience it. The Pasqual Maragall Foundation also warns that it is not necessarily hereditary.

However, latest research suggests that certain risk factors are modifiable. These are those related to cardiovascular health and lifestyle, as the Spanish Center for Cardiovascular Research’s immunologist Miguel Ángel del Pozo Barriuso indicates. Heart risk factors encompass various medical conditions, including high blood pressure, diabetes, cholesterol, smoking, and obesity. The specialist explains that controlling these depends not only on medical follow-up but also on maintaining healthy habits.

“A sedentary lifestyle and an inadequate diet can compromise cardiovascular health and, secondarily, brain health,” notes the immunologist. “There is increasing scientific evidence supporting the close relationship between both systems, reaffirming that everything that benefits the heart also protects the brain.”

II - Journey to the Center of the Science

Could treatment with psycho-stimulation and speech therapy slow the decline and provide emotional support? The foundations consulted argue that language impairment in Alzheimer’s does not progress equally in all areas. From mild stages, people already strive to speak off the cuff. Yet, their ability to understand and differentiate sounds remains relatively good, even in advanced stages.

This deterioration begins with anomia—difficulty naming objects—and can progress to global aphasia, in which language is completely lost. Language difficulties, such as anomia and paraphasias, worsen as the patient progresses through the stages of the disease. Adapting communication and using nonverbal strategies become crucial to improve interaction with those affected and mitigate emotional frustration.

Global aphasia is facing trouble when speaking and understanding language. The person can barely say words or understand what is said. Imagine trying to talk in a language you don’t know. Someone asks you questions, and you can only respond with sounds or single, meaningless words.

Anomia interferes with remembering names and specific objects. People know what something is used for but cannot recall its name. For example, someone with Alzheimer's might point to a "watch" and describe it by saying, "That thing that tells the time... the thing you wear on your wrist..."

Paraphasias consist of saying the wrong word instead of the intended one. It may sound similar or be a different word. It can happen when the patient wants to ask for “bread” but says “belly” or even “telephone” instead.

These hurdles are common and affect everyday communication. The most important thing is to classify the stages. In the early phase, mild memory issues and personality changes appear. In the moderate stage, there are barriers to performing everyday tasks without confusion. Finally, in the advanced stage, there is total dependence on care and hygiene, resulting in a significant loss of physical and mental abilities.

“It affects nearly 50 million people”

Alzheimer’s is a neurodegenerative disease that, according to the World Health Organization (WHO), affects nearly 50 million people. Thus, it becomes a challenge for modern medicine today, as there is no cure. In 2020, a study by the Faculty of Medicine of the University of Alcalá de Henares revealed that the areas with the highest Alzheimer’s mortality rates in Spain are located on the Mediterranean periphery of the peninsula. In 2017, places like Navarra, Teruel, Castellón, and Barcelona had the highest peak.

Every September 21st, the WHO and family associations commemorate this day in honor of the 900,000 people in Spain who account for AD, more than half of all dementia cases in the country.

The Spanish Society of Neurology (SSN) warns about the high level of underdiagnosis. Many mild cases are not detected early, and this delay, which can exceed two years, prevents patients from accessing early treatment. Symptoms worsen.

Globally, medical research has made key advances, such as the approval of drugs to slow the progression of Alzheimer’s. However, in Europe, “the European Medical Association (EMA) takes greater precautions in approving certain treatments to ensure they work well,” says Dr. Marc Suárez-Calvet, a neurologist at Hospital del Mar and researcher at the Pasqual Maragall Foundation in Barcelona.

The neurologist conducts research from his office on Wellington Street, next to Pompeu Fabra University. There, he supervises students enrolling in master’s degrees offered to explore specific topics such as the role of blood tests. These tests help provide a rapid diagnosis with or without symptoms.

“Alzheimer’s develops when the brain plaques produce an excess of the beta-amyloid protein, essential for the information transmission between neurons, and a decrease in another protein, positive tau, worsening cognitive processes,” says Suárez-Calvet. In other words, it works as if a swarm of bees steals honey from a hive; the honey supporting the hive disappears.

According to the SSN, before the first symptoms of Alzheimer’s appear, toxic plaques form between neurons, damaging them. These plaques have proteins, essential molecules in almost all cellular processes in our body. The Alzheimer’s Association in the U.S. classifies this disease as the most common form of dementia. In addition, the Pasqual Maragall Foundation ponders that it is closer to home than we think: one in two people has a direct or indirect relationship with it.

III - The milestone of blood biomarkers

Scientists have been diligent in creating treatments that do more than relieve symptoms. They aim to change how Alzheimer’s disease progresses. Dr. José Terencio, the Vice President of Innovation and New Technologies at Grifols, a company focused on immunology and AD, highlights this shift in medical research toward slowing it down.

In this context, the search for an Alzheimer’s vaccine has gained prominence in recent years. Researchers in Barcelona, ​​supported by the Pasqual Maragall Foundation and Araclon Biotech, a Grifols subsidiary, have been working on ABvac40, the first Spanish Alzheimer’s vaccine. Then again, it is unknown whether it will be released to market in the short term, as stated in the company’s December 2023 press release. It depends on individual hope, whether we prefer to have it or ignore it.

“The results of the Phase 2 clinical trials are encouraging, as they have shown a significant reduction in disease progression in patients in early stages,” Terencio says. Grifols claims that treatment with ABvac40 showed a reduction of up to 38 percent in disease progression.

Recently, the European Medical Association (EMA) approved a new drug: lecamenab. Though it does not mean there is a cure, it offers hope by slowing its progression. Several medications represent a step forward by targeting the core of Alzheimer’s and attacking it viciously. Still, its availability remains subject to additional approvals.

For now, let’s get back to real life. There is a breakthrough. Dr. Suárez-Calvet emphasizes that treatment focuses on controlling symptoms and, at the same time, improving the quality of patients and their caregivers. These are the people who require the most assistance and who may suffer long-term consequences. According to the Barcelonaβeta Brain Research Center (BBRC) project, of which the doctor is a part: “The diagnosis of AD involves a comprehensive evaluation, which includes medical history, cognitive testing, and neuroimaging.”

“Blood biomarkers are perhaps one of the most important discoveries in recent years in the field of Alzheimer’s,” says Suárez-Calvet. This innovation allows the disease to be detected through a simple blood test, avoiding more invasive methods such as lumbar puncture. “In some university hospitals, we have already begun to implement this method,” he adds, proving how this practice is beginning to change current medical use. The doctor adds that the development of new treatments, such as anti-amyloid therapies, seeks to modify the progression of the disease, detect it early, and empower decision-making.

Imagine the brain is a large library, and you want to know if there are any damaged books. A lumbar puncture is like reviewing old library records—the cerebrospinal fluid. A little of that fluid is extracted from the back to see if there are signs that something is wrong, such as a buildup of rare proteins. Then, Positron Emission Tomography (PET) or Amyloid PET is an advanced neuroimaging test that can detect the buildup of beta amyloid plaques in the brain. That is like using a special flashlight to look for dust spots on books, but directly on the shelves—the brain. A tracer is injected that glows in the presence of amyloid plaques—linked to Alzheimer’s—and then a scan is done to see if they are there. Both methods look for the same thing, but from different angles: one reviews the traces in the files, and the other shines light on the shelves to look for dust specks.

The Pasqual Maragall Foundation has been one of the pioneers in using blood biomarkers in the preclinical phase. This stage, without symptoms, is critical for early diagnosis. Biomarkers begin to rise ten to twenty years before AD signs appear.

The neurologist Suárez-Calvet in the lab (photo by César Cruz Requejo).

The doctor (left) and César Cruz Requejo (right) (photo by Paula Ortiz, Lab Manager of BBRC).

Suárez-Calvet’s laboratory, established three years ago, is rich in cutting-edge research. In the lab, there is a project called SIMOA, which consists of an innovative machine: the Single Molecule Array. This machine stands as an ultrasensitive technology that allows for the detection of very low protein concentrations. It is a thousand times more sensitive than traditional methods.

Before the new equipment, researchers had to rely on the Swedish University of Gothenburg to perform these analyses, causing time and access limitations. The new machinery, nevertheless, allows the studies to be autonomous while also optimizing time and experimental capacity.

The results have been validated in nearly 900 participants from three international studies: the Alfa Study in Barcelona, ​​the TRIAD study at McGill University in Montreal, and a group of patients from a Parisian hospital. All analyses were performed at the University of Gothenburg using the SIMOA HD-X.

“We are convinced that in the near future we will be able to detect silent changes in the brain with a simple blood test requested by the primary care physician,” adds Suárez-Calvet. “This will allow intervention before neuronal damage becomes irreversible.”

Yet, Alzheimer’s is complex and has no single cause. Genetic factors, such as the APOE4 gene, and environmental factors, such as pollution, play roles in its development. In demographic terms, Suárez-Calvet repeats that it is more prevalent in women. The incidence is higher in women than in men. Although the exact reason is unclear, this pattern highlights the need for a unique approach to research and treatment.

“I hope that in the coming years, we can provide quality of life to patients,” the doctor admits. “It is essential,” Suárez-Calvet concludes by inviting us to collaborate hand in hand with the scientific community. “It is what Americans call a physician-scientist; neuropsychologists collaborate with us and other specialists to further our knowledge.”

IV - Better safe than sorry

Foundations emphasize that AD affects both the patients and caregivers alike. The care required by patients may be intensive. Over the years, society has disagreed on treatment. Some hire services, but others take the reins to look after their family members. The latter may be logical, as some family organizations inform that the costly care and treatment may be overwhelming in advanced stages.

Dr. Mariana Muñoz, a follow-up specialist at the Doce de Octubre Hospital in Madrid, claims that day centers have become a pillar for patient care. Therefore, she deems it an ideal option. These centers not only offer a safe place but also give families a break, allowing them to continue with their daily activities while knowing their loved ones are in good hands. Muñoz establishes a follow-up visit every six months, during which patients are provided with a mobile phone and given questionnaires to monitor cognitive decline.

“Despite promising advances in the field of diagnosis and treatment, Alzheimer’s remains arduous to treat.” Dr. Mariana Muñoz emphasizes that clinical trials continue to face challenges, such as the strain in evaluating the long-term efficacy of treatments and the need to develop safe medications that slow the disease progression.

In this condition, everything is debated. From how one wants their family member to be treated to the science behind it. From where the family members will be taken care of to who will look after them. From which medication they will take to how costly it may get. From being in an advanced stage to remaining in a mild state. In any case, everyone we talk to agrees that something is happening. And we need to act on it, but who is right then?

V - From the core to the future

The most evident question for specialists is: how does the disease evolve? Does it ever stop? Alejandro and Pedro, who faced the frustration of undergoing the turmoil firsthand, remain unanswered.

In the oceans of human wisdom, where minds sail for answers, calm waters offer hope. As the storm of Alzheimer’s threatens to set sail, it is advisable to follow a clear course: a diet rich in omega-3s, learning new skills, and physical and mental activity. It seems like no one’s consolation, but as rhetoric evolves, it never hurts to grasp the dullness of everyday life and transform it into a future filled with somewhat more pleasant expectations.

Neurology advances, and so do the dreams of finding land in sight. To achieve this, the compass of science guides us with a haven from the winds of oblivion: a good book where words, like the gears of a clock, help us remember the time. But, in a sigh filled with mystery, the question arises: who knows if, as in Jules Verne’s novels, all these solutions are merely a map to a future yet unknown or a future that may be called fiction today but might as well become true.