We cannot yet predict who will develop dementia and who will not.
Una década antes de que la memoria comience a fallar, la química de la sangre ya puede susurrar lo que viene: dos estudios publicados en The Lancet revelan que proteínas mensurables en adultos de mediana edad señalan el riesgo de Alzheimer con años de antelación. El hallazgo no es aún una herramienta clínica, sino una encrucijada ética y científica: saber no equivale a poder curar, y el conocimiento prematuro puede infligir su propio daño. La humanidad se encuentra, una vez más, ante la paradoja de ver el horizonte sin poder alcanzarlo todavía.
- Análisis de sangre detectan marcadores moleculares del Alzheimer en personas de 56 a 69 años sin síntomas, con un riesgo hasta doce veces mayor de deterioro cognitivo para quienes los portan.
- La promesa choca con una realidad incómoda: los únicos fármacos disponibles apenas ralentizan la enfermedad un 27% y cuestan 25.000 euros anuales sin cobertura pública en España.
- Los expertos advierten que una cribado masivo generaría una avalancha de falsos positivos, sembrando alarma en personas que quizás nunca desarrollarán demencia.
- Ensayos clínicos con pacientes asintomáticos están en marcha, y su resultado podría redefinir en pocos años si intervenir antes de los síntomas cambia realmente el curso de la enfermedad.
- El debate de fondo divide a la comunidad científica: ¿basta con tener biomarcadores para recibir un diagnóstico de Alzheimer, o son necesarios también los síntomas?
Dos estudios publicados esta semana en The Lancet describen un posible punto de inflexión en la detección del Alzheimer: análisis de sangre capaces de identificar las huellas moleculares de la enfermedad en personas de mediana edad que se sienten perfectamente bien, sin pérdida de memoria ni señales de deterioro cognitivo.
El primero siguió a 1.350 personas de entre 56 y 69 años durante al menos 35 años. Aproximadamente el 6% ya portaba variantes de las proteínas beta-amiloide y tau —características del Alzheimer— pese a no tener diagnóstico cognitivo. Quienes presentaban dos marcadores específicos multiplicaban por cuatro su riesgo de problemas de memoria verbal; en algunos casos, la probabilidad pasaba de uno en cien a doce en cien. El equipo de Kristine Yaffe, de la Universidad de California en San Francisco, argumenta que esta detección temprana importa porque hasta el 30% del riesgo de demencia puede prevenirse con ejercicio, hábitos saludables y estimulación cognitiva, y porque los nuevos fármacos lecanemab y donanemab solo funcionan en las fases más iniciales.
El segundo estudio explora un trazador experimental llamado MK6240 que, mediante tomografía por emisión de positrones, detecta la acumulación de proteínas antes que los métodos convencionales —escáneres cerebrales o punción lumbar—, abriendo otra vía hacia el diagnóstico precoz.
Sin embargo, los expertos piden cautela. Pascual Sánchez Juan, director científico de la Fundación CIEN, advierte que la baja prevalencia de estos marcadores en la población general haría que un cribado masivo produjera muchas falsas alarmas, y que ningún fármaco puede revertir aún el curso de la enfermedad. Las investigadoras finlandesas Anna Rosenberg y Tiiia Ngandu señalan que el poder predictivo de estos marcadores se debilita en personas más jóvenes y que las pruebas no son apropiadas para la población general.
Juan Fortea, neurólogo del Hospital Sant Pau de Barcelona y coautor del segundo estudio, ve el campo ante dos visiones en pugna: quienes exigen biomarcadores y síntomas para diagnosticar la enfermedad, y quienes consideran que los biomarcadores solos deberían bastar. Fortea cree que el cribado poblacional es prematuro, pero podría volverse viable en pocos años si los ensayos en curso demuestran que intervenir antes de los síntomas modifica el curso de la enfermedad. Mientras tanto, personas sanas ya solicitan pruebas privadas, y la pregunta de fondo sigue sin respuesta: saber que el riesgo existe, ¿cambia realmente el destino?
Two studies published this week in The Lancet describe a potential turning point in how we might catch Alzheimer's disease—not when it arrives, but years before the mind begins to fail. Researchers in the United States have found that simple blood tests can reveal the molecular signatures of the disease in middle-aged people who feel perfectly fine, who show no signs of memory loss or mental slowdown. The discovery raises an urgent question: should we be screening everyone for these invisible markers, or would that create more harm than help?
The first study followed 1,350 people between 56 and 69 years old, all of them cognitively healthy at the start, all of them tracked for at least 35 years. Researchers led by Kristine Yaffe at the University of California in San Francisco measured two proteins in their blood—variants of beta-amyloid and tau—that accumulate in the brains of Alzheimer's patients. About 6 percent of the participants already carried these molecular markers, even though they had no diagnosed cognitive problems. But when the researchers looked closer, these people showed subtle signs of mild cognitive impairment: their memory was slightly weaker, their mental processing slightly slower. Those with two specific markers—Aβ42/40 and p-tau217/Aβ42—faced dramatically elevated risk. The Aβ42/40 marker alone increased the risk of verbal memory problems more than fourfold. For someone carrying it, the chance of developing such problems jumped from one in a hundred to twelve in a hundred.
Yaffe's team argues that this early detection matters because roughly 30 percent of dementia risk can be prevented through straightforward interventions: exercise, a healthy lifestyle, cognitive engagement. Two new drugs, lecanemab and donanemab, cannot cure Alzheimer's but can slow its progression modestly—by about 27 percent over 18 months—if given in the earliest stages. The blood tests, they suggest, could identify people in middle age who might benefit from these interventions and medications before irreversible damage occurs.
A second study, also published in The Lancet, explores a different detection method. Currently, doctors confirm Alzheimer's biomarkers through brain scans or by extracting cerebrospinal fluid through a spinal tap—reliable but expensive and invasive procedures. A new experimental tracer called MK6240, developed by the American company Lantheus, uses positron emission tomography to detect Alzheimer's proteins in the blood. In nearly 700 cognitively healthy participants aged 50 to 89, this method identified protein accumulation earlier than conventional diagnostic approaches, potentially opening another path to earlier detection.
Yet experts are sounding alarms about rushing into widespread screening. The Spanish Society of Neurology estimates that more than half of mild Alzheimer's cases go undiagnosed, and there is typically a two-to-three-year gap between first symptoms and official diagnosis. But Pascual Sánchez Juan, a dementia specialist and scientific director of the CIEN Foundation, cautions that these findings, while valuable for research, are not yet ready for clinical application. The 6 percent of middle-aged people showing markers will probably develop dementia within a decade, he notes, but because the prevalence is low, a general screening program would produce many false alarms. More troubling: no drugs currently exist that can reverse Alzheimer's course, only slow it. "This type of test would not be justified outside of research," he says, "and no one should worry about getting one unless they have recognizable cognitive symptoms."
Anna Rosenberg and Tiiia Ngandu, researchers at Finland's Institute for Health and Welfare, add another concern: the predictive power of these markers weakens in younger people. They warn that blood tests are "not appropriate for large-scale screening of the general population." The core problem remains unsolved: we cannot yet reliably predict which people carrying these markers will actually develop dementia and which will not.
Juan Fortea, a neurologist at Hospital Sant Pau in Barcelona and coauthor of the second study, sees the field at an inflection point. Two competing visions are emerging: one holds that Alzheimer's diagnosis requires both biomarkers and symptoms; the other, championed by patient advocacy groups, argues that biomarkers alone should constitute a diagnosis. Fortea believes population screening is premature but could become viable within years if pharmaceutical trials demonstrate that intervening before symptoms appear actually works, and if researchers develop reliable risk calculators—tools similar to those already used for heart disease or cancer screening. Raquel Sánchez-Valle, who coordinates the Spanish Neurology Society's dementia research group, sees both promise and peril. These tests can help researchers select participants for intervention trials, some already underway, that may yield answers within years. But healthy people are already requesting private testing, and the flood of false positives could overwhelm both patients and clinicians with information that has little predictive value for any individual. The real test, she suggests, will come when we know whether intervening before symptoms appear actually changes the disease's course.
Citações Notáveis
This type of test would not be justified outside of research, and no one should worry about getting one unless they have recognizable cognitive symptoms.— Pascual Sánchez Juan, dementia specialist and scientific director of the CIEN Foundation
The predictive power of these markers weakens in younger people, and blood tests are not appropriate for large-scale screening of the general population.— Anna Rosenberg and Tiiia Ngandu, researchers at Finland's Institute for Health and Welfare
A Conversa do Hearth Outra perspectiva sobre a história
Why does it matter that we can detect these proteins a decade before symptoms show up if we can't cure the disease anyway?
Because the new drugs work only in the earliest stages, before the brain damage becomes irreversible. If we can identify people ten years ahead of time, we might slow or even prevent the cognitive decline altogether—but only if we catch them before symptoms appear.
So the blood test is really just a tool to find candidates for drug treatment?
Partly, yes. But it's also about lifestyle. Thirty percent of dementia risk is preventable through exercise and healthy living. A blood test could motivate people to make those changes while there's still time.
But the article mentions false positives. What does that actually mean for someone who tests positive?
It means you might carry these protein markers and never develop dementia. You could live your whole life with them in your blood and stay cognitively sharp. Right now we can't tell who will progress and who won't.
That sounds like it could cause a lot of unnecessary anxiety.
Exactly. That's why the experts are cautious about screening everyone. If you tell a healthy 60-year-old they have Alzheimer's markers, you've potentially created a patient out of someone who might never get sick.
What would change their minds about screening?
If drug trials prove that treating asymptomatic people actually works. And if we develop reliable risk calculators—like we have for heart disease—that can tell individuals their real probability of getting sick. Then screening becomes justified.