New Study Finds Test of Protein Levels in the Eye a Potential Predictor of (Future) Alzheimer’s Disease

Low levels of amyloid-β and tau proteins, biomarkers of Alzheimer’s disease (AD), in eye fluid were significantly associated with low cognitive scores, according to a new study published in the Journal of Alzheimer’s Disease. Led by researchers at Boston Medical Center, the study is the first to connect these known AD protein biomarkers in the eye to mental status. These findings indicate that proteins in the eye may be a potential source for an accessible, cost-effective test to predict future Alzheimer’s disease.

Diagnosing and starting treatment for AD before symptoms begin is key to managing the disease, because by the time symptoms appear it is often too late for current treatments to have any meaningful effect. Abnormal amounts of amyloid- β and tau proteins are biomarkers of AD, and deposits of amyloid proteins in the brain begin many years prior to symptoms of the disease. Previous research has shown an association between low levels of amyloid-β and tau proteins found in the cerebrospinal fluid obtained by lumbar puncture tests and preclinical AD, when pathological changes of AD present in the brain, but before the onset of clinical symptoms. However, lumbar puncture tests are expensive and inconvenient for many patients to undergo.

In this study, researchers used samples of eye fluid from 80 patients who were previously scheduled for eye surgery. The fluid extracted during these surgeries is typically discarded. Researchers tested the eye fluid to determine the levels of amyloid-β and tau proteins, and correlated those levels to the results of a baseline cognitive test. Low levels of these biomarker proteins were significantly associated with lower cognitive scores among the patients.

“These findings could help us build an accessible, and minimally invasive test to determine Alzheimer’s disease risk, especially among patients with eye disease,” says Lauren Wright, MD, first author on the study and ophthalmology fellow at BMC. “We noted that some of the participants who had low levels of protein biomarkers in their eye fluid already had signs of mild to moderate dementia based on their cognitive scores.”

These results reaffirm previous studies suggesting that patients with eye disease are at-risk for the development of AD, and suggest that further investigation in patients with eye disease may yield results that could be generalizable to larger populations.

“This is a great step in discovering the eye’s potential role in diagnosing preclinical Alzheimer’s disease, and further study is needed comparing protein biomarkers in the eye with more in-depth neurological testing,” adds Manju Subramanian, MD, senior author, principal investigator, and ophthalmologist at BMC.

Source: Boston Medical Center


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Brain Scans Spot and Track Alzheimer’s Disease

Brain scans can improve diagnosis and management of Alzheimer’s disease, a new study claims.

Researchers assessed the use of PET scans to identify Alzheimer’s-related amyloid plaques in the brain. The study included more than 11,000 Medicare beneficiaries with mild thinking impairment or dementia of uncertain cause.

This scanning technique changed the diagnosis of the cause of mental impairment in more than one-third of the participants in the study.

The brain scan results also changed management — including the use of medications and counseling — in nearly two-thirds of cases, according to the study published April 2 in the Journal of the American Medical Association.

“These results present highly credible, large-scale evidence that amyloid PET imaging can be a powerful tool to improve the accuracy of Alzheimer’s diagnosis and lead to better medical management, especially in difficult-to-diagnose cases,” said study co-author Maria Carrillo, chief science officer of the Alzheimer’s Association.

“It is important that amyloid PET imaging be more broadly accessible to those who need it,” she added in an association news release.

Funding for the study came from Avid Radiopharmaceuticals Inc., General Electric Healthcare, and Life Molecular Imaging.

“We are impressed by the magnitude of these results, which make it clear that amyloid PET imaging can have a major impact on how we diagnose and care for patients with Alzheimer’s disease and other forms of cognitive decline,” said lead author Dr. Gil Rabinovici. He’s a professor of neurology at the Memory and Aging Center at the University of California, San Francisco.

There is no cure for Alzheimer’s disease, but early diagnosis means that patients can receive treatment to manage symptoms and be directed to clinical trials for new drugs.

Early diagnosis also means that patients and families can plan for the future, including safety, care, legal and financial issues, and access resources and support programs, the researchers said.

In this study, the PET scans revealed that about one-third of patients previously diagnosed with Alzheimer’s had no significant amyloid buildup, and their Alzheimer’s diagnosis was reversed.

But in nearly half of patients not previously diagnosed with Alzheimer’s, the PET scans revealed significant amyloid plaque buildup, resulting in a new diagnosis of Alzheimer’s.

One-third of the study participants who had previously been referred to Alzheimer’s clinical trials showed no sign of amyloid buildup based on PET scans. Based on those results, doctors were able to ensure that nearly all (93 percent) of patients referred to Alzheimer’s trials were amyloid-positive, which is critical to these trials’ success.

“Accurate diagnoses are critical to ensure patients are receiving the most appropriate treatments. In particular, Alzheimer’s medications can worsen cognitive decline in people with other brain diseases,” Rabinovici said.

“But perhaps more fundamentally, people who come into the clinic with concerns about memory problems want answers. An early, definitive diagnosis may allow individuals to be part of planning for the next phase of their lives and to make decisions that otherwise would eventually need to be made by others,” he said.

Source: HealthDay


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When it comes to Alzheimer’s disease, early detection is not the end but the beginning . . . . .


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Scientists Find a Link between Diabetes and Risk of Alzheimer’s Disease

Emily Gersema wrote . . . . . . . . .

Patients on medication for type 2 diabetes may be keeping Alzheimer’s disease at bay.

USC Dornsife psychologists have found that those patients with untreated diabetes developed signs of Alzheimer’s disease 1.6 times fasterthan people who did not have diabetes.

The study was published in the journal Diabetes Care.

“Our findings emphasize the importance of catching diabetes or other metabolic diseases in adults as early as you can,” says Daniel A. Nation, associate professor of psychology at USC Dornsife College of Letters, Arts and Sciences. “Among people with diabetes, the difference in their rate of developing the signs of dementia and Alzheimer’s is clearly tied somehow to whether or not they are on medication for it.”

Nation says that this study may be the first to compare the rate of developing the pathology for Alzheimer’s disease and dementia among people with normal glucose levels, with prediabetes, or people with type 2 diabetes — both treated and untreated.

For the study, the scientists were comparing the “tau pathology” — the progression of the brain tangles that are the hallmark of Alzheimer’s disease. When the tangles combine with sticky beta-amyloid plaques — a toxic protein — they disrupt signals between brain cells, impairing memory and other functions.

Nation and Elissa McIntosh, a USC Dornsife Ph.D. doctoral candidate in psychology, analyzed data collected by the Alzheimer’s Disease Neuroimaging Initiative on nearly 1,300 people age 55 and older. Data included biomarkers for diabetes and vascular disease, brain scans and a range of health indicators, including performance on memory tests.

For some participants, Nation and McIntosh were able to analyze 10 years’ worth of data, while for others, they had one or four years.

Among 900 of those patients, a little more than 50 had type 2 diabetes but were not being treated, while nearly 70 were receiving treatment. Most people in the study — 530 — had normal blood sugar levels while 250 had prediabetes (hyperglycemia).

The researchers compared, among the different diabetic patient categories, the brain and spinal fluid test results that can indicate signs of amyloid plaques and the brain tangles.

“It is possible that the medicines for treating diabetes might make a difference in the progression of brain degeneration,” Nation says. “But it’s unclear how exactly those medications might slow or prevent the onset of Alzheimer’s disease, so that is something we need to investigate,” Nation says.

Increasingly, scientists regard Alzheimer’s disease as the result of a cascade of multiple problems instead of just one or two. The compounding factors range from pollution exposure and genetics (the ApoE4 gene, for instance) to heart disease and metabolic disease.

Source: University of Southern California


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Hormone Therapy Linked to Slight Rise in Alzheimer’s Risk

Serena Gordon wrote . . . . . . . . .

Many women turn to hormone therapy to ease some of the more troubling symptoms of menopause, such as hot flashes and night sweats.

But new research suggests that relief may come at a cost — an increased risk of Alzheimer’s disease.

The study found that women taking hormone therapy had a 9 percent to 17 percent higher risk of developing Alzheimer’s disease. In women who began taking hormone therapy before age 60, this increased risk was tied to long-term use of a decade or longer.

“The take-home message is that, in absolute terms, nine to 18 excess diagnoses of Alzheimer’s disease per year will be detected in 10,000 women aged 70 to 80, especially in those women who had used hormone therapy for over 10 years,” said study senior author Dr. Tomi Mikkola. He is an associate professor in the department of obstetrics and gynecology at Helsinki University Hospital in Finland.

The study was published online in the BMJ, along with an accompanying editorial.

One of the authors of that editorial, Dr. JoAnn Manson, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said the findings from this study are “not a cause for alarm.”

“Overall, the research has been reassuring for younger women in early menopause who are seeking treatment for night sweats and hot flashes. Based on the totality of evidence, there appears to be relative safety for hormone therapy when taken in early menopause,” she said.

Manson also pointed out that due to the study’s design, it can only show an association, not a cause-and-effect relationship.

It’s been almost 20 years since concerns were first raised about the possible health effects of hormone therapy, including increased heart and cancer risks. Studies since then have often had mixed results, including studies looking at memory and thinking abilities in women taking hormone therapy.

Some research has suggested that women who take hormones to ease menopausal symptoms may be less at risk of developing Alzheimer’s disease, while others show no harm or benefit. Now, the latest study suggests a possible increase in risk.

Both Mikkola and Manson said hormone therapy shouldn’t be used specifically to try to prevent Alzheimer’s disease.

But, if you’re a woman experiencing menopausal symptoms that are affecting your quality of life, Manson said, “concern about Alzheimer’s disease or cognitive [thinking] decline should not interfere with menopausal symptom management.”

However, Mikkola noted that any woman taking hormone therapy for 10 years or more should be advised that they may have an increased risk of the memory-robbing disorder.

The study looked at nearly 85,000 postmenopausal women diagnosed with Alzheimer’s in Finland from 1999 to 2013. The researchers compared these women to women who hadn’t been diagnosed with Alzheimer’s disease.

Nearly all of the women with Alzheimer’s were diagnosed after 60. More than half were over 80 at the time of diagnosis, the findings showed.

The investigators reviewed health records to see if women were taking hormone replacement therapy. If they were, the researchers looked to see how long they had been taking it.

There are a number of different forms of hormone replacement therapy, including pills, patches, gels and creams. Ninety percent of hormone replacement therapy is given by pill in Finland, the study authors noted.

Three-quarters of the women had been taking hormone therapy for more than 10 years, according to the report.

The study didn’t find a difference in Alzheimer’s risk based on the formulation of hormone therapy. The risk was similar whether women took estrogen alone, or estrogen and progesterone together.

Mikkola explained that “the absolute risk increase for Alzheimer’s disease is small,” and said that the study “emphasizes the fact that hormone therapy should be used in recently menopausal women for symptom relief and if they benefit from the therapy.”

Editorial author Manson said that the decision about whether or not to use hormone therapy has to be individualized. She said a woman and her doctor have to take into account a woman’s risk factors, symptoms and preferences.

Source: HealthDay


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Sleep Apnea May Be Linked With Alzheimer’s Marker

Steven Reinberg wrote . . . . . . . . .

Millions of Americans are left drowsy each day by sleep apnea, and new research suggests it might also raise their odds for Alzheimer’s disease.

It isn’t clear, however, if sleep apnea causes the buildup of “tau” protein tangles in the brain that are a marker for Alzheimer’s, or if the increased tau helps cause the apnea, the researchers said.

“Since tau accumulation is a hallmark of Alzheimer’s disease, an increase in tau raises concern that sleep apnea could make [people] with sleep apnea more vulnerable to Alzheimer’s,” said lead researcher Dr. Diego Carvalho, a neurologist at the Mayo Clinic in Rochester, Minn.

The new study — to be presented at an upcoming meeting of the American Academy of Neurology (AAN) — is consistent with previous work suggesting that sleep apnea increases the risk for dementia, he said.

“However, it is also possible that Alzheimer’s disease could predispose people to sleep apnea or that there is a bidirectional relationship between sleep apnea and Alzheimer’s disease,” Carvalho said.

Obstructive sleep apnea is a chronic condition that can cause breathing to stop frequently during sleep. Tau, a protein that forms tangles in the brain, is found in people with Alzheimer’s.

For the study, Carvalho’s team looked at 288 people, aged 65 and older, without thinking and memory problems. Each study participant had brain scans to look for tau tangles in the part of the brain involved in memory and perception of time. This area, part of the temporal lobe, is more likely than other brain areas to accumulate tangles.

In addition, the researchers asked participants’ bed partners if they ever had seen them experiencing sleep apnea; 43 participants who had such episodes were identified.

Those participants had nearly 5 percent more tau than people without sleep apnea episodes. That finding remained even after Carvalho’s team considered other factors linked to tau levels, including age, sex, education, cardiovascular risk factors and other sleep problems.

The study has several limitations, the researchers noted. The number of participants was small. No sleep studies were done to confirm suspected apnea, and it was unclear whether participants were already being treated for it.

“People who have apneas during sleep should seek medical attention to confirm the diagnosis of sleep apnea and treat it, if indicated,” Carvalho said.

More study is needed to gauge whether treating sleep apnea prevents tau buildup and reduces dementia risk, he added.

Rebecca Edelmayer, director of scientific engagement at the Alzheimer’s Association, reviewed the study.

“These findings align with a lot of the data we’ve seen with sleep disturbances increasing the risk for cognitive impairment,” she said.

Though the specific connection between dementia and sleep is unclear, Edelmayer said it might be that the brain gets less oxygen during apnea episodes, and that stresses the brain. Sleep disturbances may also alter the brain’s circadian rhythms — the 24-hour body clock that cycles between alertness and sleepiness.

Edelmayer added that the brain solidifies memories during sleep, and interrupting that process might lead to thinking and memory problems.

“What we know now about the importance of sleep is that good sleep is really important for your overall health,” she said.

The study findings are scheduled for presentation May 4 at an AAN meeting in Philadelphia. Research presented at meetings is typically considered preliminary until published in a peer-reviewed journal.

Source: HealthDay


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