Wednesday, December 20, 2017

Synthetic Ovaries, Alzheimer in Americans over 30:

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Like heart disease and certain cancers, the risk of developing Alzheimer’s disease can likely be predicted through certain biological markers long before any signs of the disease appear.
Researchers are fast closing in on how to identify and analyze those “biomarkers.”
But in the process, they’re also discovering just how widespread signs of future Alzheimer’s are.
Almost 47 million people in the United States over the age of 30 are estimated to have signs of “preclinical” Alzheimer’s, according to a new study.
That means detectable changes that are known to eventually lead to Alzheimer’s are beginning to take place in the brain.
Researchers note it is likely years before those changes result in Alzheimer’s and impair memory or other brain functions.
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Some of the 47 million, they say, won’t live long enough for the disease to appear.
Another 3.6 million Americans already had clinical Alzheimer’s in 2017.
Another 2.4 million had mild cognitive impairment (MCI) due to Alzheimer’s, an intermediate stage of the disease in which brain function is affected even before dementia sets in.
In 2060, the researchers expect, 15 million Americans will have Alzheimer’s or MCI.

Research shows potential impact

The research is the first to forecast the extent of preclinical Alzheimer’s and MCI, according to the Alzheimer’s Association.
The research points to both a growing problem and emerging opportunities.
The new statistics indicate about a quarter of the over-30 population currently could have signs of future Alzheimer’s.
And, with the percentage of that preclinical Alzheimer’s population expected to grow to 75 million by 2060, it could eventually include about 30 percent of Americans over 30.
But it also means that, if these biomarkers are accurate, patients can be targeted for diagnosis and treatment early, much like cholesterol levels and other biomarkers can indicate future risk of heart disease, diabetes, or cancer.
The primary biomarkers indicating future Alzheimer’s are the buildup of amyloid-beta proteins in the brain and the death or loss of functionality of neurons in the brain, or neurodegeneration.
If identified early enough, the hope is doctors can design interventions that can, at the very least, delay the impending dementia and Alzheimer’s as long as possible.
Cognitive training exercises, physical exercise, and some medications have shown some signs of being effective, though the evidence is still limited.
But knowing who needs those interventions and when they might be effective is part of that progress toward treatment, said Ron Brookmeyer, PhD, professor of biostatistics at the University of California Los Angeles’ (UCLA) Fielding School of Public Health and lead author of the new study.
“We need to keep in mind how effective they are and at what point in the disease process they might be effective. Do we have interventions that could be effective at each of the points along the continuum of this long disease process?” Brookmeyer told Healthline. “If you could identify a person’s risks and screen them, what is the utility? It’s helpful for planning, but, of course, the question is, are there interventions you can do?”
In addition to pursuing better treatments, he said, the field needs to pursue better ways of predicting disease, including identifying other biomarkers and predictors, and expanding the diversity of study subjects.
His study, for instance, relied in part on data from the Mayo Clinic Study of Aging cohort, which consists of 93 percent white subjects.

An emerging portrait

But, despite the limitations, a picture of how Alzheimer’s progresses and how many people it is affecting is emerging.
That picture, according to Brookmeyer’s study, shows detectable amyloid buildup beginning as early as the 30s, but peaking in the mid-60s.
It also shows neurodegeneration starting to grow around the 40s, and peaking around age 70.
Mild cognitive impairment doesn’t generally begin until the 60s, early Alzheimer’s in the late 60s, both peaking in the mid-80s to early 90s.
For younger people, the risks are low.
“We do see a little bit of amyloid buildup in younger ages, but in terms of clinical endpoints, we don’t really see that until the 70s and 80s and above,” said Brookmeyer.
Michael Donohue, PhD, associate professor of neurology at the University of Southern California (USC) Keck School of Medicine who was not involved in the new study, pointed to previous research that has shown around 2 percent of 30-somethings may have amyloid buildup, though that rises to around 10 percent by age 50.
The older you are by the time amyloid starts building up or other biomarkers set in, the more likely you are not to develop full-blown Alzheimer’s — though only because you’re more likely to die from something else in the course of the disease’s decades-long progression.
“The disease process is very long,” Brookmeyer said.
Of the 47 million with signs of future Alzheimer’s “many of them may never experience signs or symptoms because their natural lifespan is not long enough,” he added.
A 65-year-old woman with amyloid buildup faces a strong chance of developing Alzheimer’s.
But a 90-year-old man with amyloid buildup detected for the first time likely won’t, even when accounting for the fact that the disease progresses more quickly in older people.
“So it’s not a one size fits all,” he said. “Many of us have some brain changes going on, but we may never experience signs or symptoms.”
As for determining whether you’re one of the quarter or so Americans over 30 with signs of future Alzheimer’s, that’s also still a work in progress.
Donohue pointed to the A4 Study and EARLY studies, which identify, using amyloid-detecting PET scans and spinal fluid tests, volunteers with elevated amyloid.
But, he said, insurance currently doesn’t reimburse for the PET scans and the spinal tests are mostly just used in specialized research clinics.
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  • Could Synthetic Ovaries Be Used to Treat Menopause?

    Bioengineered organs could be a new frontier for women’s health. However, some key questions still need to be answered.
    synthetic ovaries
    Human organs engineered in a lab could move from science fiction to fact soon.
    Researchers are investigating these organs as ways to treat a variety of diseases and conditions, including menopause.
    A new study examined the possibility of developing synthetic ovaries to treat symptoms associated with menopause and postmenopause.
    After ovaries stop functioning, the diminishment of key hormones put women at increased risk for heart disease and osteoporosis.
    Additionally, women face a host of symptoms that can be uncomfortable, such as hot flashes and vaginal dryness.
    While hormone replacement therapy (HRT) can mitigate many of these symptoms, research released in the early 2000s found that HRT, given via patch or pills, could significantly increase the risk of certain cancers, heart disease, and stroke.
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    As a result of this research, HRT has become less common and more controversial in recent years.
    Many women receive no HRT after reaching menopause, or are put on much smaller doses of hormones.
    Due to these risks, doctors and researchers have been looking for newer, safer options to provide women with replacement hormones.

    A look at synthetic ovaries

    One possibility could be implanting synthetic ovaries.
    These engineered organs better “mimic” real ovaries and provide the hormones at lower doses.
    A woman’s menopause symptoms can then be diminished without increasing the risk of cancer and heart disease.
    Researchers from the Wake Forest Institute for Regenerative Medicine were able to create “biosynthetic” ovaries to implant in rats to see if they could mitigate some menopause symptoms.
    They isolated two cells contained in the ovary called the theca and the granulosa. Then, they managed to encapsulate them into a thin engineered membrane and implant them into the rats, according to their study published earlier this month in Nature Communications.
    The ovary did not make eggs that would result in the rats becoming fertile.
    “The treatment is designed to secrete hormones in a natural way based on the body’s needs, rather than the patient taking a specific dose of drugs each day,” Emmanuel C. Opara, PhD, senior author and professor of regenerative medicine at Wake Forest Baptist Medical Center said in a statement.
    Opara and his co-authors found that the rats with the engineered ovaries appeared to have better bone mineral density than the rats that received the equivalent of low hormone therapy replacement.
    It was also about equal to the rats that had high doses of HRT.
    This finding was notable since the amount of hormones released in these rats was far lower than in both the high-level and low-level HRT rats.
    The rats with the synthetic ovaries also had less weight gain and their uteruses were not as large as the rats that had both low and high doses of HRT.
    “This study highlights the potential utility of cell-based hormone therapy for the treatment of conditions associated with the loss of ovarian function,” said Opara.

    Research could open new avenues

    The research is still in the early stages.
    It will take more time and research before a long-term synthetic ovary could be considered a treatment option for postmenopausal women.
    But this study does provide a new avenue of research, which is key to finding better ways to help women.
    Dr. Avner Hershlag, chief of Northwell Health Fertility in New York, called the study “absolutely transformational.”
    He said that even though this research is in the early stages, patients have been left without many choices of treatment if they don’t pursue HRT.
    “That has really caused a crisis that is not much discussed,” he said. “It is a major problem for women. They don’t have a replacement. They don’t have anything else.”
    He pointed out that non-HRT treatments are less effective at keeping bones healthy for postmenopausal women.
    “You can give her calcium, you can give her magnesium…You can give her weight-bearing exercises,” he said. “They are not as good as estrogen.”
    Hershlag said the possibility of synthetic ovaries could potentially mean a long-term treatment for menopause symptoms while not increasing the risk of other conditions like heart disease.
    Dr. Tanmoy Mukherjee, assistant professor of obstetrics, gynecology, and reproductive medicine at the Icahn School of Medicine and co-director of Reproductive Medicine Associates of New York, said this research was “definitely exciting.”
    “Experts certainly have been waiting for some form of hormone replacement therapy that is safe, that’s effective,” he told Healthline.
    The right hormones are “important for bone health, cardiac health, cognitive function, there are multiple effects of estrogen.”

    Questions remain

    While Mukherjee said he was excited about the findings, he also said there are many questions that need answering before the synthetic ovaries could be considered as an experimental treatment for women.
    “This is what research is all about, I think it’s exciting but I think these are the questions that have to be addressed before it can be widely utilized,” he said.
    He questioned how long the device would work and whether it would be safer than the current low-dose HRT.
    “It’s hard enough to remind people to take a pill every day, let alone come in for an implantable form of hormone therapy,” he said.
    He called the surgical implantation a “big stumbling block.”
    Additionally, he pointed out that the complex relationships between hormones, heart health, and other bodily systems means that this treatment could lead to other unknown health risks.
    “Are we going to see, no matter what we do, an increase in breast cancer?” he said. “Aging is a complicated process.”
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    Written by Gillian Mohney on December 17, 2017


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