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Stopping Alzheimer’s Before Symptoms Appear

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While there are plenty of things that teenagers worry about, dementia isn’t normally one of them. Yet one new major Alzheimer’s drug trial is recruiting people as young as 18 to answer what may be the most pressing question facing the field: Can the ravages of the disease be prevented by identifying those on track to get it and treating them up to 10 years before they show symptoms?

The recent arrival of drugs that slow the cognitive decline of Alzheimer’s in many people is a welcome breakthrough, but so far their efficacy has only been demonstrated in people with mild symptoms. By the time patients are diagnosed, their brains have already undergone extensive changes. But growing evidence suggests that taking the drugs well before that damage has occurred could significantly slow the disease and possibly even stop it in its tracks.

“Now we have drugs that can slow the disease by 30 percent or so in people with symptoms, but that’s not good enough,” says Reisa Sperling, a neurologist who heads the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston. “We want to get to 100 percent, and that means preventing people from getting to the symptomatic stages.”

Earlier and earlier

In medicine, treating a disease when it is causing pathological changes in the body, but hasn’t yet progressed far enough to cause clinical symptoms, is known as secondary prevention. (Primary prevention is heading off a disease before there is any pathology, and tertiary prevention is managing symptomatic disease to slow the worsening of symptoms.) Secondary prevention has been essential to medicine’s triumphs in reducing the risks of death and disability for those with early heart disease or diabetes. Doctors don’t wait for someone to have a heart attack before prescribing a cholesterol-lowering statin or for someone to suffer artery or kidney damage before putting them on metformin to control blood sugar.

In 2023, the results of trials of lecanemab (brand name Leqembi) and donanemab on Alzheimer’s patients with mild cognitive impairment suggested that medicine may now have the tools to bring secondary prevention to bear on the disease. Both drugs are monoclonal antibodies that target the hardened clumps of protein called amyloid plaque that form in the brains of Alzheimer’s patients.

Although much is still unknown about the mechanisms of Alzheimer’s, there is little question now that the buildup of plaque precedes symptoms by many years. In the lecanemab and donanemab trials, the earlier patients were along the long road to plaque buildup, the better the drugs did in removing most of the plaque and slowing cognitive decline. “It’s when you remove nearly all the plaque with one of these drugs that you see the real benefits in terms of symptoms,” says Randall Bateman, a physician and professor of neurology at Washington University School of Medicine.

Because patients with even mild symptoms already have a large buildup of plaque, testing the notion that plaque-fighting drugs can be more effective earlier in the buildup process means enlisting presymptomatic patients for trials. “Studies are moving toward people who are just at the borderline for being positive for plaque and treating them to try to keep them from accumulating more of it and from having symptoms,” says Susan Abushakra, a physician and researcher who is vice president of clinical development and medical affairs at Alzheimer’s-focused biotech company Alzheon in Framingham, Mass.

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https://static.scientificamerican.com/dam/m/10562d4469742764/original/waterfall.jpg?w=900Joey Guidone/Theispot

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Click the link below for the article:

https://www.scientificamerican.com/custom-media/davos-alzheimers-collaborative/stopping-alzheimers-before-symptoms-appear/

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