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The future of Alzheimer’s treatment, beyond the symptoms

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The effects of dementias rob people of their cognitive ability: to remember, to find words that they want to use, of attention, concentration, of certain special abilities that they previously had and, in general, of their functionality for daily life. It is a syndrome with several causes, and the disease of Alzheimer’s it’s one of those ways.

The earliest manifestation of dementia is called mild cognitive impairment. Through biomarkers, imaging technology and lumbar punctures to obtain spinal fluid and possibly blood plasma measurements, a fairly accurate diagnosis can be made as to whether this deterioration is, in fact, due to Alzheimer’s, says the American neurologist Ronald Petersen, director of the Mayo Clinic Alzheimer’s Research Centeras well as the Clinic for the Study of Aging.

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Petersen also talks about two types of treatment. One is focused on symptoms, and has been in use for two decades. Here are the cholinesterase inhibitors, which increase the amount of the neurochemical acetylcholine in the brain, to keep cells working longer. In that group are also the donepezilthe galantamine and the rivastigmine. And a fourth drug is memantinewhich works on a different neurochemical system.

Dr. Ronald Petersen, neurologist and researcher on aging and Alzheimer’s. Photo: The Universe

“But these are all temporary fixes for symptoms,” says Petersen, and they’re meant to stabilize, not improve. So the next field of action is the disease-modifying therapies, which target the two targets of Alzheimer’s, amyloid beta and tau proteins. LAmyloid-lowering treatments will complete their final stages of evaluation (Phase 3) in the coming months.

What has been the clinical impact of these therapies that are in their last months of research? Petersen recalls that in 2021 the Food and Drug Administration (FDA) gave accelerated approval to the drug aducanumabbased on the results of one of his two phase 3 clinical studies. It was a controversial decision, he acknowledges, since ‘accelerated approval’ means the FDA believes aducanumab does do what it promises, reducing amyloid beta levels in the brain (certified by a positron emission tomography or PET scan). “However, they were less convinced that this would have a significant clinical impact. So it’s a tentative approval.”

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What remains to be confirmed, then, in the coming months, is that the reduction caused by aducanumab will have the desired impact. Along with this medicine there are two more that have the same purpose. “Preliminary data indicates that they all work well, but the key is what is going to be the result of that amyloid reduction.”

Imaging tests are part of the battery of tools for diagnosing Alzheimer’s and other types of dementia. Photo: Shutterstock

That would mean that In the short term, there would be three products designed to slow the progression of cognitive decline in patients. “They are not to improve memory or to think better,” Petersen specifies, adding that measuring the true impact on the population that begins to decline due to Alzheimer’s will be challenging. What is the opinion of the neurologist? “I think that if there is a positive effect it will be small, my personal feeling is that these drugs will not be cures for the disease. They are not like penicillin,” he warns, and if an analogy had to be made, it could be with cholesterol-lowering diseases, which do not cure heart disease, but reduce the speed with which the person could develop it.

What is mild cognitive impairment?

Dr. Petersen mentions more than occasional forgetfulness, a consistent pattern. “I’m not remembering as well as I used to, or not as well as I still should at my age. I am starting to forget information that I used to easily remember about myself and my family.” They are not forgetfulness due to distraction, but they can interfere with activities of daily living, working, driving, paying bills. “To the casual observer it seems normal, but you and your family who know you know that it is not like it used to be.” And that should be investigated, it’s a clinical sign.

Can mild cognitive impairment be prevented? If it’s Alzheimer’s, marked by the presence of those two proteins, beta amyloid and tau, Petersen says the answer is that at this point it’s not certain it’s possible to prevent. “However, if we are talking about the dementia syndrome, which I am not thinking about as well as before, there are many factors at play, and here we are talking about lifestyles: aerobic exercise, staying intellectually active, playing games, talking, attending classes or conferences, keeping the mind in shape”.

Early lifestyle changes play an important role in slowing cognitive decline. Photo: Shutterstock

And of course, the diet. “It is not the only one, but we can mention the Mediterranean diet, with nuts, fruits and vegetables, lean meats, fish, maybe a sip of wine.” Also, stay connected to your authentic social networks (not only virtual). Interact with family and friends, avoid the tendency to withdraw.

take care of your sleep hygiene. If you have a breathing disorder like sleep apnea, be sure to treat it, because poor sleep can impair thinking and memory. Y reduce stress unnecessary.

Alzheimer’s isn’t just a memory problem.

When talking about the loss of cognitive functions, it is associated with forgetfulness, but Petersen says that There are other aspects of the dementias, including Alzheimer’s, that have behavioral manifestations such as depression, anxiety, apathy, and personality changes.

“There are other dimensions of neurodegenerative diseases, one of them is temporal frontal dementia, and it means that the person will engage in inappropriate conduct; before he knew how to behave, and now he asks questions or has socially unacceptable attitudes; is disinhibited, repairs loudly about the physical appearance of others or makes sexual comments in environments in which it is not accepted. When that is part of the change, says the neurologist, it is conceivable that part of the frontal lobes of the brain have been impacted by the disease, as part of the degenerative process.

The effect of dementias can manifest as withdrawal, apathy, depression and anxiety. Photo: Shutterstock

Alzheimer’s isn’t just genetic either. Yes, it has these components, like almost all diseases, but the genetic form of the disease affects perhaps one percent of the affected population. The other 99% suffer from something that doctors call sporadic disease, that is, not determined (entirely) by genes, such as cancer, diabetes and hypertension.

If you have a family history of these diseases, you are more likely to inherit them, but this is not a sentence. “If you have a confirmed case in your family through autopsy or biomarkers that indicate it is Alzheimer’s and not another type of dementia, you have a slightly higher risk than the general population,” says Petersen, but asks not to take it for granted or resign yourself. , but start early to have the lifestyle discussion. (YO)

Source: Eluniverso

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