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This article is published in number 14 of Vanity Fair on newsstands until April 4, 2023

Among the hottest scientific topics worldwide is the study of neurodegenerative diseases. The last few months have been characterized by a dense production of analyses, research and new treatments aimed at offering additional support in the management of pathologies still without a cure. The recent case of the actor Bruce Willis, who retired from the scene with a diagnosis of frontotemporal dementia, has further amplified the attention on the subject, arousing interest and concern at the same time. The story of the hero’s disease Die Hard is having a large following on the net. A few days ago, I came across an article published on the scientific site Medscape in which the American neuroscientist Michael Merzenich highlights the differences between the disease that struck the 68-year-old actor and other more common forms of dementia, usually associated with old age. Merzenich, professor emeritus of the University of California-San Francisco, famous for his pioneering studies in the field of neuroplasticity, explains in an article titled Bruce Willis’ frontotemporal dementia it’s not your grandfather’s dementia, that in other forms of mental decline, cognitive losses can be profound, but emotional self-control and verbal fluency are generally less impaired. The disease that struck Willis, on the other hand, initially manifested itself with aphasia and emotional control difficulties, without the actor himself realizing it. A particular form of dementia, according to the luminary, for three reasons: it can arise in relatively young individuals, between 50 and 60 years of age; it has little initial impact on memory and instead creates difficulties in language and behavior management; produces the loss of a special group of neurons, called von Economo (which in nature we share with monkeys, whales, elephants), crucial for social behavior and the sense of self. If the disease follows its classic course, Willis may experience a slow mental disconnect over time and a progressive loss of judgment, emotional control and understanding of what is happening around him and why. This could be compounded by a deterioration in the management of bodily functions and general health.

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Merzenich’s article only partially satisfies my curiosity. I wonder how many forms of dementia exist and, above all, how we can distinguish the symptoms.
The answer is complex, I realize it when I collect Michela’s testimony. Her father is 80 years old and has been diagnosed with frontotemporal disease. Unlike Willis, in this case the onset was behavioral. “The affected area of ​​the frontotemporal lobe is the one that governs planning ability and awareness of the consequences of actions,” says Michela. “It’s kind of like he’s back in adolescence, when you do things on impulse, without thinking.” The discovery of the disease, in fact, took place following a striking fact. “We understood that something was wrong when an eviction request came from the landlord: my father had stopped taking care of all the financial part of his life. He no longer paid the rent or the condominium expenses and this problem didn’t worry him: he minimized it ». Michela explains to me that another characteristic of the disease is precisely the absence of empathy: those who suffer from it do not understand that their behavior can put them in difficulty. This form of dementia can have a genetic origin or occur spontaneously for still unknown reasons. And it is said that the symptoms are not perceived immediately. «My mother and I realized it in 2021. The thing that cares about this pathology is that until something sensational happens you don’t notice it. Only the CAT scan revealed that the brain was damaged, but no one can say how long this went on.” Today he is still independent, she writes although he reads little, cooks and drives. “Sometimes, however, he gets lost on some things, for example he struggles to plan and manage certain daily tasks”. There is no cure for frontotemporal dementia: Michela’s father only does periodic checks to monitor the progress of the disease.

Not all forms of dementia appear and evolve in the same way. He explains it to me Elvira DeLeonibus, director of the neuropsychopharmacology group of the Institute of biochemistry and molecular biology of the Cnr and group leader of the Telethon Institute of Genetics and Medicine of the Telethon Foundation. I contact her because I know that she has been doing research on dementias and brain mechanisms for years. “Dementia is the generic term used to define cognitive decline in memory, such as Alzheimer’s disease, which is the most common form of all,” she says. «In the frontotemporal variant, however, the first symptoms can be more similar to those of a psychiatric illness, with loss of impulse control. There is also a third variant, the dementia with Lewy bodies, which appears in older age and has some structural differences: in almost all dementias, protein aggregates are formed in the brain. In the frontotemporal it is the tau protein that aggregates and accumulates in the frontal lobe, in the one with Lewy bodies it is alpha-synuclein, which also has a very close association with Parkinson’s disease, so sometimes the two pathologies occur Together. What unites these variants is the final clinical picture with memory disturbances, spatial disorientation, cognitive, executive and motor decline. What differentiates them instead are the initial stages and the age of onset which depend on the brain area most affected: the frontal lobe or, in the case of Alzheimer’s disease, the temporal lobe.

Currently, in Italy, people affected by a form of dementia are about 1 million, most of them with Alzheimer’s. Population aging could lead to an increase, mainly among women. Elvira De Leonibus is studying precisely this prevalence of female cases, the causes of which are not yet known. «The incidence with which these forms occur in the female population appears to be greater especially in the case of Alzheimer’s. The progression is also faster and the symptoms more severe », she points out. “What you’re trying to figure out is whether there are indeed differences in the way women use their brains. Given the importance of constant brain training, the basic idea is to see if the regions most sensitive to decay are used less by women in favor of other circuits. The hypothesis is that we women tend to use cognitive strategies that favor some brain areas to the detriment of others which, however, are more sensitive to the effect of age and passing time».

A recent study by the University of Cambridge has shown that the signs of neurological decline can appear up to nine years earlier than the actual onset of the disease. But the Cnr researcher widens the perspective. «The brain is a system capable of compensating for the small defects we have. When memory begins to decline we write the shopping list, if we forget where we parked the car we mark the position on the smartphone, if we have many commitments an electronic agenda reminds us of everything. We are “delegating” our memory and therefore have eliminated a very important stimulating factor. The problem, therefore, is that we can hardly pay attention to the small alarm bells. However, through a PET, today there is the possibility of visualizing the protein aggregates that accumulate in the brain and in certain studies it has been seen that in some subjects they are present even fifteen or twenty years before the onset of mild cognitive decline”.

Is it then possible to intervene on the signs of neurological decline before it is too late? «The general perception is that there is no cure for these diseases, so we prefer not to know. Early diagnosis, on the other hand, is very important, but it would also involve an ethical problem: if it is discovered that you have a slight cognitive defect – and it is not said that it will necessarily lead to dementia – how will this information be used? To answer, we are trying to understand which mild cognitive defects are the best predictors of these diseases. What is certain is that absolute protective factors are constant physical activity, low consumption of alcohol and cigarettes and above allsystematic mental training: serves to create cognitive reserves that make some areas more resistant to aging and the attacks of time. Let’s not forget that cognitive decline physiologically begins very early: starting from the age of 40″.\

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Source: Vanity Fair

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