With Covid we have become accustomed to hearing about “frail” people, and among them are always counted the elderly. But frailty is a complex, multidimensional concept and, as recent research conducted by IRCCS Fondazione Don Carlo Gnocchi ONLUS in Milan on the neural stages of frailty shows, it manifests differently in women than in men. This means that different strategies need to be used to cope with it, which take into account how people of both sexes really age. Francesca Baglio, neurologist and one of the authors of the study “Differential Roles of Neural Integrity, Physical Activity and Depression in Frailty: Sex-Related Differences” published in Brain Science, explains.

Dr. Baglio, what really is age-related frailty?

To begin with, it should be made clear that the date on one’s birth certificate is not an objective parameter on which we can rely. There is, however, a biological ageDifferent from chronological age. It is a measure of the body's ageing, based on the effectiveness of the mechanisms that keep cells young and on markers of the functionality of organs and apparatus. that is associated with resilience, that is, the ability to recover following an external stress, for example, influenza. To put it simply, we all know that there are elderly people in excellent condition, who are called “robust,” and others who are less “frail,” and this depends on their physiological reserves, including neural reserves. We can understand frailty as a progressive decline in clinical condition: it is not a pathology but a syndrome.

Do women become frail in the same way as men?

No, women and men have two different profiles. In women, frailty is often associated with mood alterations, especially depression. That, however, in turn is also a risk factor for other neurological conditions, such as sleep disorders, cognitive impairment, and neuropsychic slowing. Depression has a very high prevalence: it affects one in two women over 70.

In men, however, we observe more often a physical weakening: reduced physical activity, sedentariness, and loss of both agility, endurance to exertion, and muscle strength. In short, we can talk about increasing fatigability, which can be assessed with specific scales. Reduced levels of physical activity could then explain an increase in all cardiovascular risk factors in the male population.

Finally, as far as cognitive aspects are concerned, the domain of language is the one that is often impaired with age in men, while in women it is mainly memory that is affected.

Can this information be used to devise treatment strategies to slow down the aging process?

Of course it does. In men, intervention should be aimed primarily at stimulating exercise to regain lost activity levels or prevent further loss. Incidentally, in the male, stimulating physical activity also has a positive impact on indices of neural integrity. In general, however, aerobic physical activity and re-training to exercise works as a good ‘fertilizer’ for the brain.

In women, on the other hand, counter-depression approaches are needed, through drug therapies when necessary, but also through the promotion of group activities and engagement to regain socialization in daily life. In our work, for example, we have considered dance-based rehabilitation approaches because it is not only a physical but also a socializing activity that also has an important impact on depression, and both cognitive and memory recovery. Nordic walking or group trekking are other great activities for both sexes.

Regarding chronic diseases such as, for example, cardio-cerebrovascular or pulmonary diseases, are there differences?

Yes. In men, as opposed to women, there are more associated chronic conditions that pose greater risks to life in the short term: we are talking, for example, about heart failure or COPD – chronic obstructive pulmonary disease – where exacerbations pose an immediate risk. Moreover, the same diseases occur, on average, in a more severe form in men than in women.

This might explain what we call the frailty paradox: older women often have more comorbidities [the simultaneous presence in the same person of two or more diseases] than men and are generally more frail, yet they are longer lived.

Going back to countering frailty, what approaches are used?

The best approach is always multidimensional, physical and cognitive together, taking into account gender and, tailored to who we are dealing with.

For example, we are doing interventions with physiotherapists mediated by music in patients with neurodegenerative diseases: music allows for the activation of many neural pathways and thus exercise not only for motor strengthening of balance and mobility, but also for the recovery of social and cognitive skills.

In the case of people with heart disease, however, we send people to attend centers that also do physical activity outdoors, such as Nordic Walking.

In women, then, we focus a lot on cognitive enhancement pathways, especially for memory. Neural pathways are like roads that need to be continued to be maintained, and based on a person’s cognitive picture, we go on to design pathways to enhance their residual abilities or cognitive compensation strategies. More and more electrical neurostimulation techniques are also being used, which are well tolerated as they have no serious adverse effects with long-term effect.

Finally, hearing loss is another risk factor of frailty that needs to be addressed because it leads people to isolate themselves. It should be talked about a lot more to get people to address this problem, because there is still a stigma attached to it.

Does dietary supplementation also play a role in prevention?

With no drugs available for neurodegenerative conditions-except for symptomatic ones such as antidepressants-nutraceuticals can add to all the interventions we have discussed. There are purpose-designed supplements, with a whole range of evidence from studies showing how certain active ingredients and their combinations act against the mechanisms of oxidation, or by promoting the well-being of blood vessels and, consequently, of cerebral perfusion. Some useful active ingredients are glutathione precursors such as polydatin, N-Acetyl Cysteine (Nac) and other combined amino acidsAmino acids are the basic substances that make up proteins. Each protein is characterized by a precise sequence of amino acid "bricks". Some are produced by the body by processing food, others, which the body cannot synthesize, must be taken directly with food., which in my experience, for example, are very useful in counteracting so-called mental fog. Other active ingredients that regulate homocysteine have been shown to be useful in the prevention of cerebro-cardiovascular comorbidities.

Where can we find prevention pathways like the ones you described?

Generally, people turn to the NHS when it is late, when the disability is apparent, whereas it would be useful to activate these pathways to prevent frailty much earlier. Think about the fact that many neurodegenerative diseases are triggered 20 or even 30 years before symptoms appear. We should begin campaigns to assess known risk factors as early as middle age, in adults from age 50, to intervene early with targeted strategies.

First, however, it is crucial for people to be aware of this.