From the novel to the mobile: hunting for the first signs of Alzheimer's

Irish writer and philosopher Iris Murdoch was diagnosed with Alzheimer's in 1997. She died two years later, at the age of 79, and the study of her brain confirmed the signs of the disease: beta-amyloid protein plaques and tau protein tangles. But when might the first symptoms of cognitive decline have appeared? In 2004, researchers from the Institute of Cognitive Neuroscience at University College London published in the journal Braina comparative study of three novels: the first, Under the Net, from 1954, her most highly valued work; The Sea, the Sea, from 1979; and the last one she released, Jackson's Dilemma, from 1995, poorly received by critics. The study showed that the vocabulary used by Murdoch had decreased and the language had been simplified.

Can the literary works of an author serve to detect early symptoms of Alzheimer's? In 2014, researchers at the University of Groningen, in the Netherlands, published a much broader analysis with a new methodology and involving six authors: Iris Murdoch, Gerard Reve, and Hugo Claus, who were diagnosed with Alzheimer's; Agatha Christie, who is suspected to have had the disease; and P.D. James and Harry Mulisch, who did not develop it. Published in Cortex, the study reveals an impoverishment of the works in the first four cases: reduced vocabulary, more general and less concrete terms, more repeated phrases and words, and greater use of pronouns instead of proper nouns. These changes, however, were not observed in James and Mulisch.

Could a person's texts be used to predict the disease in advance? For Gonzalo Sánchez Benavides, a researcher at the BarcelonaBeta Brain Research Center of the Pasqual Maragall Foundation and the Hospital del Mar Medical Research Institute, "with people who write diaries recurrently, it would be possible." According to this researcher, "with patients in general it is very difficult," because an extensive written record of each person is needed.

The voice as a diagnostic and prognostic tool

While the texts may suggest symptoms of Alzheimer's, it is very important to detect them in the early stages of the disease, because early diagnosis allows for interventions to be planned, while a medication that can cure or alleviate the disease in advanced stages does not yet exist. Now, explains Sánchez Benavides, research into voice biomarkers is on the rise. The patient's responses and narratives are recorded and transcribed to analyze lexical and syntactic aspects, as well as to explore acoustic aspects. This way we can see if the language has a certain complexity or lexical richness. "When there is cognitive impairment, circumlocutions are often used, such as saying 'bring me that' instead of the specific name. With acoustic analysis we can detect, for example, patterns of longer pauses in the middle of a sentence and not at the end, as most people usually do," points out this expert.

There are already algorithms capable of detecting these characteristics and research is underway so that they can be predictive of the disease long before the symptoms are visible. For the moment, however, they are not yet consistent enough to reach clinical application.

Sánchez Benavides and other researchers from the BarcelonaBeta Brain Research Center –such as Oriol Grau‐Rivera, Andreea Radoi, and Clàudia Porta‐Mas– participated in an international study published this May in Alzheimer & Dementia, which demonstrated that a system of markers in oral speech had proven effective for detecting early signs of Alzheimer's. It was conducted with five European cohorts that together involved 736 participants. A correlation was observed between these biomarkers and those revealing the presence of amyloid-beta and tau protein in cerebrospinal fluid. The authors, however, note that before reaching clinical practice, it must still be validated with large population groups.

Studies are also being conducted where it is not necessary to know the content of a person's text or oral speech. For example, Benavides and other researchers are analyzing typing patterns on mobile phones. The rhythm or the time taken to move from one side of the keyboard to the other can reveal signs of cognitive impairment. This is already being done with multiple sclerosis, and now the goal is to find a method that allows it to be applied to dementias.

The nuns and cognitive reserve

In 1986, David Snowdon, an epidemiologist and professor of Neurology at the University of Kentucky, and his team began a long-term study with the nuns of the School Sisters of Notre Dame in Saint Louis, Missouri (USA). The goal was to take advantage of the fact that they all had the same lifestyle and routines and that upon entering the congregation, they had provided brief autobiographies. In total, it included 678 Catholic nuns, who underwent cognitive tests at various times and most of whom donated their brains to science upon death.

Among the various results obtained in this long-term study, in 2000 they published in the Annals of the New York Academy of Sciences that after analyzing the writings made by 74 nuns when they were between 19 and 37 years old and their brains when they died, between 78 and 97 years old, they found that low linguistic ability was linked to subsequent cognitive problems and neurological development. They also observed that the nuns who had shown more complex and rich writing could have amyloid plaques and tau tangles in the brain, but had not developed dementia. This, explains Dr. Sánchez Benavides, is due to the so-called cognitive reserve: “Whoever has led an intellectually rich life may have signs of Alzheimer's in the brain, as autopsies reveal, but not show symptoms of capacity loss in life or show them later”.

This shows, first, that texts written at relatively young ages can serve to predict that there may be cognitive losses in the future. And, second, that making the brain work, by reading, writing, debating, memorizing, can help to delay and even prevent cognitive impairment, despite the presence of amyloid and tau. As with everything, there are exceptions and cases are known of intellectually active people who have developed Alzheimer's. This may be due to unknown genetic or environmental reasons. “It is impossible to know –explains Dr. Sánchez–, but it seems clear that intellectual practice and formal education protect against dementia”.