{"id":1475722,"date":"2024-07-07T02:10:00","date_gmt":"2024-07-07T06:10:00","guid":{"rendered":"https:\/\/bugaluu.com\/news\/?p=1475722"},"modified":"2024-07-07T02:10:00","modified_gmt":"2024-07-07T06:10:00","slug":"should-alzheimers-be-treated-before-it-becomes-symptomatic-experts-weigh-in","status":"publish","type":"post","link":"https:\/\/bugaluu.com\/news\/should-alzheimers-be-treated-before-it-becomes-symptomatic-experts-weigh-in\/1475722\/","title":{"rendered":"Should Alzheimer’s Be Treated Before It Becomes Symptomatic? Experts Weigh In"},"content":{"rendered":"

Should Alzheimer’s Be Treated Before It Becomes Symptomatic? Experts Weigh In<\/span><\/p>\n

\n

Authored by Robin Seaton Jefferson via The Epoch Times,<\/em><\/a><\/p>\n

In March, the U.S. Food and Drug Administration (FDA) issued a revised draft guidance<\/a> to help drug companies develop medication to treat cases of early Alzheimer\u2019s disease that \u201coccur before the onset of overt dementia.\u201d<\/p>\n

One theory about Alzheimer\u2019s is that amyloid pathology can occur decades before symptoms appear, and to stop the disease, doctors may need to address this underlying pathology well before that happens. Some say that will label people as having a disease they may never develop; others say it\u2019s the only way to stop it in those who will come to have it.<\/strong><\/p>\n

<\/a><\/p>\n

Treat Dementia Like Heart Disease<\/h2>\n

Rudolph E. Tanzi, who has a doctorate in neurology and is a professor of neurology at Harvard Medical School and the director of its Genetics and Aging Research Unit, said that to stop dementia and Alzheimer\u2019s, doctors must treat it the way they currently treat heart disease.<\/p>\n

\u201cJust like we keep track of cholesterol and alter lifestyle and take safe drugs to lower cholesterol levels in order to avoid heart disease, we will need to do the same for Alzheimer\u2019s disease,\u201d Mr. Tanzi told The Epoch Times. \u201cThe FDA guidance is a step in that direction.\u201d<\/strong><\/p>\n

The American Heart Association reports that death due to heart disease has declined<\/a> by 60 percent since 1950 and that the number of people in the United States dying of a heart attack each year has dropped from one in two in the 1950s to one in 8.5 today. Mr. Tanzi said that is because doctors now treat their patients proactively for a disease that could otherwise kill them many years in the future.<\/p>\n

As a geneticist who co-discovered three of the first Alzheimer\u2019s disease genes, Mr. Tanzi replicated the cascades of cellular changes<\/a> in Alzheimer\u2019s in a petri dish so scientists could conduct tests as the disease developed and test drug efficacy. He said the problem is now that doctors don\u2019t diagnose Alzheimer\u2019s disease until the brain has already deteriorated to the point of dysfunction. Patients \u201cneed safe and affordable drugs to intervene with amyloid deposition as early as possible,\u201d he added.<\/p>\n

Mr. Tanzi said that although the guidance is correct to advise treating early-stage Alzheimer\u2019s patients, scientists will still someday need to prevent the buildup of abnormal amyloid deposits as soon as they begin in the brain before damage occurs.<\/strong><\/p>\n

\u201cThis would be most important for those with early-onset familial Alzheimer\u2019s disease gene mutations, those with Down syndrome, and carriers of the APOE epsilon variant that increases risk for Alzheimer\u2019s disease, where you know amyloid deposition is guaranteed or highly likely beginning early in life,\u201d Mr. Tanzi added.<\/p>\n

Is Amyloid Positivity Enough to Redefine Alzheimer\u2019s Disease?<\/h2>\n

But there is still no solid proof that any drugs, even if they reduce amyloid, will decrease dementia fates in the future, said Dr. Eric Widera, a professor of clinical medicine in the Division of Geriatrics at the University of California\u2013San Fransisco. He also questions the risks of some drugs with serious side effects, such as brain bleeding<\/a> and death<\/a>.<\/p>\n

There is a trend to redefine Alzheimer\u2019s disease based on whether someone is amyloid positive on a test, \u201cindependent of whether an individual has any symptoms of cognitive impairment, or whether they will develop them in the future,\u201d Dr. Widera said.<\/strong><\/p>\n

He explained that while scientists do have \u201cpretty good evidence that in individuals with mild cognitive impairment and mild dementia,\u201d two drugs, donanemab and lecanemab, \u201chave an exceptional ability to remove amyloid.\u201d However, he argues that this ability has only a \u201csubtle effect\u201d on the rate of decline in cognition.<\/p>\n

\u201cThis is pretty clear evidence that suggests amyloid is likely not the only factor that contributes to Alzheimer\u2019s disease progression and that we have a lot yet to learn about how to stop or reverse the disease,\u201d he said.<\/p>\n

The changes proposed will have effects that are \u201cfar from subtle\u201d and will be marketed as \u201ca new Alzheimer\u2019s epidemic,\u201d<\/strong> said Dr. Widera.<\/p>\n

An estimated 6 million Americans aged 65 and older live with Alzheimer\u2019s and dementia, with the majority being over age 75. \u201cThe proposed changes will move what is a feared but far from universal disease of aging, Alzheimer\u2019s dementia, to a largely silent, asymptomatic disease affecting a much larger population, as most people with positive amyloid biomarkers have no cognitive issues,\u201d Dr. Widera wrote in his commentary<\/a>, published in February in the Journal of the American Geriatrics Society.<\/p>\n

What Can Be Done?<\/h2>\n

For his part, Mr. Tanzi agrees that much more must be done. \u201cWe will need blood tests that tell us not only when amyloid is already doing its damage in the brain, but also tests that can tell us when to treat so as to prevent amyloid deposition in the brain in the first place.\u201d<\/p>\n

Mr. Tanzi said Alzheimer\u2019s is only \u201cbeatable\u201d when predicted early, based on family history and genetics; detected early, based on blood biomarkers and imaging; and intervened upon early, using safe and affordable drugs.<\/p>\n

\u201cThe approved amyloid drugs, like Leqembi [lecanemab], are not approved for prevention, but only for treatment in the mildest cases of Alzheimer\u2019s disease. That is good to do, but still too late.\u201d He added that lecanemab \u201cis too costly, at over $60,000 per year, including the necessary MRIs to detect brain swelling and hemorrhage.\u201d<\/strong><\/em><\/p>\n

He said that is one of the focuses at the McCance Center for Brain Health, where he is currently fundraising for an Alzheimer\u2019s disease clinical trial initiative to test combinations of repurposed safe and affordable drugs and natural products to lower amyloid levels in the brain, as a safer and more affordable alternative to amyloid immunotherapy like lecanemab.<\/p>\n

\u201cThe hope is that combinations of safe and affordable repurposed drugs can someday be used in tens of millions of Americans to prevent Alzheimer\u2019s disease,\u201d <\/strong><\/em>he added.<\/p>\n

What Will the Guidance Do?<\/h2>\n

As a draft, the document will \u201cserve as a focus for continued discussions\u201d for the treatment of early Alzheimer\u2019s disease, the draft states. However, when finalized, the document \u201cwill represent FDA\u2019s current thinking regarding the selection of subjects with early [Alzheimer\u2019s disease] for enrollment in clinical trials and the selection of endpoints for clinical trials in this population.\u201d<\/p>\n

With its proposed guidelines, the FDA is focusing more on amyloid. It considers the reduction of brain amyloid, found by positron emission tomography (PET scans), to be a surrogate endpoint that is \u201creasonably likely to predict clinical benefit\u201d and that clinical trials showing an effect on that surrogate endpoint can be the basis for accelerated approval, including for drugs intended to treat Alzheimer\u2019s.<\/p>\n

According to Fierce Biotech, a company that reports on the biotech industry, the FDA isn\u2019t going as far<\/a> as to say that amyloid reduction can be considered a primary endpoint\u2014the main result measured at the end of a study to see whether a given treatment worked\u2014in Alzheimer\u2019s trials. However, the agency suggests that this biomarker can serve as a surrogate endpoint\u2014an indicator that tells if a treatment works\u2014to predict clinical benefit.<\/p>\n

Alzheimer\u2019s researchers currently use both cognitive and functional measures as co-primary endpoints, resulting in a two-year or less average clinical trial duration in the symptomatic stages of the condition. But it could take longer to establish clinically meaningful treatment effects among patients with early Alzheimer\u2019s due to limited or nonexistent cognitive and functional deficits seen early on. Plus, tools often used to measure functional impairment in patients in the later stages of Alzheimer\u2019s may not be able to identify subtle changes in early-stage disease.<\/strong><\/p>\n

For these reasons, the FDA is considering other approaches, including endpoints based on cognitive assessments or surrogate endpoints, which may allow for shorter trial durations in the earliest stages of disease, Fierce Biotech reported.<\/p>\n

Possibility of Overdiagnosis<\/h2>\n

In a draft document<\/a> published in October 2023, the Alzheimer\u2019s Association Workgroup suggested expanding the criteria for Alzheimer\u2019s diagnosis and basing diagnosis on core biomarkers such as amyloid rather than clinical syndromes.<\/p>\n

The American Geriatrics Society (AGS) commented on the criteria expansion<\/a>, expressing concerns that it would \u201cplace many older and multimorbid people at risk of overdiagnosis, which in turn could lead to initiation of treatments with as yet unproven clinical benefit, particularly in an asymptomatic population, and high potential for harm.\u201d<\/p>\n

The AGS said the document fails to pay sufficient attention to the potential impact of an Alzheimer\u2019s diagnosis on patient identity or any social and fiscal consequences.<\/p>\n

\u201cThe reality is that many biomarker-positive individuals never develop cognitive impairment … and most people diagnosed with dementia will die with, not of, dementia,\u201d <\/strong><\/em>the AGS wrote.<\/p>\n

\u201cAt this juncture, a cognitively normal 50-year-old would have a 1 in 10 chance of testing positive for amyloid … and then carry an [Alzheimer\u2019s disease] diagnosis in their health records,\u201d<\/strong><\/em> the organization wrote.<\/p>\n

The AGS added that this \u201cdistracts from the broader aim of ensuring high quality health care for individuals who already have cognitive impairment or dementia.\u201d<\/p>\n

Citing the \u201cpotential influence of financial ties between key stakeholders who make decisions on definitions and diagnostic thresholds,\u201d the AGS said transparency is critical, and any conflict of interest should be disclosed.<\/strong><\/p>\n

The Epoch Times contacted the FDA and the Alzheimer\u2019s Association Workgroup but did not receive a reply.<\/p>\n<\/div>\n

Tyler Durden<\/a><\/span>
\nSat, 07\/06\/2024 – 22:10<\/span><\/p>\n

\u200bhttps:\/\/www.zerohedge.com\/medical\/should-alzheimers-be-treated-it-becomes-symptomatic-experts-weigh<\/a>\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"

Should Alzheimer’s Be Treated Before It Becomes Symptomatic? Experts Weigh In Authored by Robin Seaton Jefferson via The Epoch Times, In March, the U.S. Food…<\/p>\n","protected":false},"author":0,"featured_media":1475723,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1475722","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","wpcat-1-id"],"_links":{"self":[{"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/posts\/1475722","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/comments?post=1475722"}],"version-history":[{"count":0,"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/posts\/1475722\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/media\/1475723"}],"wp:attachment":[{"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/media?parent=1475722"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/categories?post=1475722"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bugaluu.com\/news\/wp-json\/wp\/v2\/tags?post=1475722"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}