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*A one-two punch of chronic disease*
By JUDY SIEGEL-ITZKOVICH
05/04/2014
Neuroscientist Prof. Michal Beeri has returned from a decade in New York to investigate the connection between diabetes and Alzheimer’s disease.
 
The world faces two major epidemics of chronic disease – diabetes, with some 350 million sufferers, and Alzheimer’s disease, with an estimated 40 million.

The prevalence of each disorder is expected to double or even triple within a few decades, threatening the income of patients’ families and the economic health of nations that will be forced to treat and care for sufferers.

But could it be that they pack a one-two punch – that one may cause the other, or at least significantly raise the risk of contracting the other? In recent years, there has been growing evidence that excessive sugar in the bloodstream increases the likelihood of the most common type of dementia decades later.

“Years ago, when insulin-dependent type-1 diabetics did not receive optimal care, none of them were at risk of developing Alzheimer’s disease because they didn’t live long to get it,” said Prof. Michal Beeri, director of the Joseph Sagol Neuroscience Center (JSNC) of Sheba Medical Center at Tel Hashomer.

However, Beeri stressed that this connection was not necessarily an automatic death sentence. Research has indicated that the more type-2 and type-1 diabetics maintain glycemic (blood sugar) control, the less likely they are to develop Alzheimer’s.

“Such people may have diabetes for many, many years and still not develop dementia.

In addition, there are diabetics who carry specific genotypes that may strongly increase their risk to develop dementia, while those without such genotypes will not have to worry so much.”

An Israeli-born neuroscientist and geriatric and rehabilitation psychologist, Beeri has published over 85 peer-reviewed papers.

Her career has been fully devoted to the study of cognitive impairment, Alzheimer’s disease and other types of dementia.

“My father is Brazilian and my mother [is] from Chile. We lived in several countries, including Ethiopia, Brazil and Iran,” she said in an interview with The Jerusalem Post.

“I have two brothers, both of whom live in Brazil. I always thought I’d be a businesswoman, but studied both business and psychology.”

Then she worked for three years in a brain and behavior animal lab at the Hebrew University of Jerusalem. Beeri went on to do her doctoral degree at Bar-Ilan University in Ramat Gan on Alzheimer’s disease and priming (in which exposure to one stimulus influences a response to another, such as remembering the word “nurse” when it follows “doctor” better than if it is followed by “bus”). Then she, her hi-tech businessman husband and three children – now aged 17, 15 and 10 – left for New York City, where they spent a decade. Michal worked at the Mount Sinai School of Medicine and the Veterans Hospital in the Bronx and conducted much research in cognitive aging.

“I went directly to a faculty position at Mount Sinai instead of doing post-doctoral work. My love for research in Alzheimer’s and dementia originated in 1995 when I began my doctoral work. Prof. Michael Davidson opened a memory clinic at Sheba, where I did my PhD. Then, two years ago, Sheba vice president for research and development Prof. Shlomo Noy asked me to come and lead the Sagol Neuroscience Center.

I still have an academic position at Mount Sinai and return to New York every other month where I have a research team,” she said.

Beeri became very passionate about studying dementia. “My grandpa on my mother’s side was diagnosed at 76 with Alzheimer’s and died of it at 83, and a grandfather on the other side had type-2 diabetes.

At Sheba, she was named head of the JSNC, funded by Joseph Sagol’s son Sami Sagol to coordinate and initiate innovative and groundbreaking research in the field of brain sciences. Drawing on the considerable resources of Sheba, which is the country’s largest medical center, it coordinates the research of over 100 physicians and scientists studying the central nervous system. Established in 2004, it has promoted many scientific studies and trained numerous PhD and MSc graduates in neuroscience.

The JSNC employs investigators and doctors who integrate groundbreaking basic and clinical research of the brain to facilitate translational research in the field. The center, said Beeri, maintains many collaborations within Sheba, in addition to joint research with other Israeli centers and academic research institutes abroad, such as in the US, the UK, the Czech Republic and Japan. The JSNC has executed a wide variety of scientific studies and shaped new knowledge.

Joseph Sagol established the first Keter Plastics factory in the 1950s, and in the early 1980s handed responsibility for the management of Keter Plastics to his son Sami, who turned it into the Keter Group, one of the world’s leading manufacturers and marketers of plastic consumer products.

Keter has several plants worldwide and employs 4,000 workers, half of them outside Israel. The Keter Group comprises about 30 companies here, the US and Europe.

The future of brain research and its funding was a central theme last fall at Israel’s first-ever International Brain Technology (Israel Brain Tech) Conference. The Tel Aviv event, attended by Sami Sagol, hosted leaders from a wide range of disciplines, including Nobel laureates, investors, scientists and technologists. IBT uses a collaborative model for tackling brain-related conditions by behaving like a “social organization, bringing together a diverse group of people who might otherwise never have had a chance to meet and exchange ideas,” she said.

Beeri noted that because of the ever-increasing life expectancy throughout the Western world, neurodegenerative diseases like Alzheimer’s are becoming more and more common. The elderly are the fastest- growing population group in many developed countries – and in the US alone, where healthcare expenses reach a fifth of national and personal income, people over 65 will comprise half of the national population by 2030.

Sagol contributes to other brain science centers around the country as well – such as the Sami Sagol School of Neuroscience at Tel Aviv University and the University of Haifa’s Sagol Department of Neurobiology, with its interdisciplinary science, especially memory and learning processes and also a center for gene manipulation in the brain.

In addition, Assaf Harofeh Medical Center in Tzrifin houses the Chamber of Hope for Brain Repair, less formally known as the Sagol Hyperbaric Chamber. The world’s largest center for hyperbaric medicine for brain repair research and treatment, it treats 80 patients a day.

Already in 2004, when at Mount Sinai, Beeri and colleagues published in the prestigious journal Neurology a paper called “Diabetes mellitus in midlife and the risk of dementia three decades later.” They looked at nearly 1,900 people who had originally been among the 10,000 male civil servants studied 30 years before in the Israeli Ischemic Heart Disease Study.

“This was initiated in 1963 by Prof. Uri Goldbourt. The reason only men were included then is that it was thought that women did not get significant amounts of coronary disease.”

The average age of survivors was 82. Comparing those who had been diagnosed in midlife with type-2 diabetes and those who had not, the scientists found that those who had diabetes were almost three times more likely to develop Alzheimer’s disease decades later.

“Since 2004, I have been increasingly interested in diabetes and Alzheimer’s,” she continued. “We worked on very early markers for Alzheimer’s, and these included studies on nutritional factors and medications that work on the immune system,” Beeri noted. “Nothing really worked. There are some medications approved by the US Food and Drug Administration that offer some level of help to something like 30 percent to 40% of the patients. They may delay the course of Alzheimer’s in some of them, but we can’t predict who they will be. When the first signs of dementia show up clinically, it is usually too late, as lots of brain cells have already died.”

Thus it is important to detect early markers for the condition. “If you don’t know what the markers are, you don’t know when and what to treat. It may be very complex,” she said.

She noted that the Helen Bader Foundation in Wisconsin funded the establishment at Sheba of the Israel Registry for Alzheimer’s Prevention.

“Helen was a wealthy woman who loved Israel and Alzheimer’s patients. She even taught the demented to dance. After she died of cancer, her estate left money for our registry,” which works in conjunction with the second-largest health fund, Maccabi Health Services. Anonymous data of 1,000 Maccabi members who developed Alzheimer’s were examined along with their risk factors, including diabetes.

“Beyond normal blood sugar levels, education is the biggest protective factor against the development of dementia,” said Beeri. Funded by the US National Institutes of Health, the researchers looked at Maccabi members with diabetes who were cognitively normal and then followed them up every 18 months. The results of pen-and-paper cognitive tests were compared with testing for HbA1C levels (which document glucose levels three months before).

“This enabled us to see how the patients’ diabetes control was and how the sugar levels affected the brain,” said Beeri. “We also sent some patients for MRI scans of their brains.”

Formal education is the primary protective factor, but even if you didn’t get a university degree, how much you activate our brain by reading or doing crossword puzzles is also protective.

“There are also new technologies for brain training that are claimed to lower the risk of dementia.”

Family history is also a factor in the development of the most common type of dementia.

“There are maybe 2 percent or 3 percent of people with an early onset, before the age of 60.

For this type, three genes responsible were discovered,” the Sheba researcher said. But the other 98% or so are largely sporadic.

“We still don’t really know what causes Alzheimer’s. The older one’s parent is if he got it, the less the adult child’s risk. While we used to think that if a person got it after 90 he had no risk of becoming demented, we don’t think so now; it just means the risk reaches a plateau. Most of us who reach 100 and beyond will get Alzheimer’s.”

Type-2 diabetes, which usually develops from overweight, poor diet and lack of exercise, is preventable if people change their lifestyle in time. One a person gets diabetes, good control of blood sugar is very important.

Beeri’s center is also running a study of the effects of type-II diabetes medications and dementia.

“Those who take both injected insulin plus oral medications to reduce their blood sugar level are likely to have fewer amyloid plaques in the brain than others, which means less pathology. But this is determined only in autopsies, so it’s just observational.”

In general, it’s a good rule that everything that is good for the heart – not smoking, observing a proper diet and engaging in regular exercise to keep a proper weight, normal blood pressure and healthy cholesterol levels – is also good for the brain, Beeri said.

As for reading to lower your risk, “I don’t mean just newspaper headlines but whole articles as well as Sudoku, crosswords and other brain teasers.”

In another 10 years, Beeri concluded, “I don’t know if we’ll find a solution to Alzheimer’s – some pill to protect or cure our brains – but we’ll be in a much better place with new technologies and maybe even surgery.”
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