Getting Diabetes Before 65 More Than Doubles Risk For Alzheimer's Disease

Diabetics have a significantly greater risk of dementia, both Alzheimer's disease — the most common form of dementia — and other dementia, reveals important new data from an ongoing study of twins. The risk of dementia is especially strong if the onset of diabetes occurs in middle age, according to the study.
"Our results . . . highlighted the need to maintain a healthy lifestyle during adulthood in order to reduce the risk of dementia late in life," explained Dr. Margaret Gatz, who directs the Study of Dementia in Swedish Twins.

In a study published in the journal Diabetes, Gatz and researchers from Sweden show that getting diabetes before the age of 65 corresponds to a 125 percent increased risk for Alzheimer's disease. Nearly 21 million people in the United States have diabetes, according to the American Diabetes Association, which publishes the journal.

This risk of Alzheimer's disease or other dementia was significant for mid-life diabetics — as opposed to those who develop diabetes after 65 — even when controlling for family factors. In other studies, genetic factors and childhood poverty have been shown to independently contribute to the risk of both diabetes and dementia.

"Twins provide naturally matched pairs, in which confounding factors such as genetics and childhood environment may be removed when comparisons are made between twins," explained Gatz, professor of psychology, gerontology and preventive medicine at the University of Southern California and foreign adjunct professor of medical epidemiology and biostatistics at the Karolinska Institute in Sweden.

Indeed, the chances of a diabetic developing Alzheimer's disease may be even greater in real life than in the study, the researchers write. They identify several factors that might have led them to underestimate the risk of dementia and Alzheimer's among those who develop diabetes before the age of 65.

Diabetes usually appears at a younger age than dementia does, the researchers note. Diabetes is also associated with a higher mortality rate, which may reduce the size of the sample of older adults. In addition, approximately 30 percent of older adults with diabetes have not been diagnosed.

The results of the study implicate adult choices such as exercise, diet and smoking, as well as glycemic control in patients with diabetes, in affecting risk for Alzheimer's disease and diabetes, according to the researchers.

The sample for the study was 13,693 Swedish twins aged 65 or older in 1998, the year tracking for dementia began. Information about diabetes came from prior surveys of twins and linkage to hospital discharge registry data beginning in the 1960s.

Weili Xu of the Karolinska Institute was the lead author of the study, which was a part of her dissertation research.

The research was supported by grants from the National Institute on Aging, the Alzheimer's Association (U.S.A.), the Swedish Research Council in Medicine, and Swedish Brain Power.

Safely Fixed Hip Prostheses

Artificial hip joints are firmly anchored to the patient’s damaged bone by screws. But which parts of the bone will safely hold the screws in place? A simulation model is to calculate the strength of the bone from computer tomography images.Hip prostheses do not hold forever. If an implant comes loose, the doctors have to replace it. Most patients need this second operation after about 15 years. By then, the first prosthesis has often worn down the pelvic bone in several places. Moreover, the bone density, and thus also its strength, changes with increasing age. Medics therefore have to work out where best to place the screws that connect the artificial joint to the bone, and what shape the hip prosthesis needs to be in order to fit the surrounding bones as well as possible.

At present, doctors examine patients using computer tomography (CT), and determine the rough density of the bones from the images. On the basis of various assumptions, they then calculate how strong the bones are in different places. The problem is that, although there are various theories on which the simulations can be based, the results often deviate significantly from reality. The consistency of the damaged bones is usually different from what the simulation leads to believe.

This is set to be changed by researchers at the Fraunhofer Institute for Machine Tools and Forming Technology IWU in Dresden and their colleagues at the biomechanics laboratory of the University of Leipzig. They are developing a model with which doctors can reliably and realistically calculate the density and elasticity of the bone from the CT scanner images. To this end, the researchers are transferring methods usually used for component testing to human hip bones, which involve inducing oscillations in the bone. This type of examination cannot be carried out on the patient. The bone has to be clamped into an apparatus.

“The nature of the oscillations enables us to deduce local properties of the bone – such as its density and elasticity,” explains IWU group manager Martin Quickert. The researchers compare these results with scanned images of the bone and describe the correlations on the basis of a mathematical model. This should make it possible in future to determine the strength of a bone directly from the CT scanner images. The scientists have already performed the first examinations on prepared and thus preserved bones, and plan to induce oscillations in unprepared bones left in their natural state over the coming months. The researchers hope that in about two years’ time, doctors will be able to obtain a realistic simulation model of unprecedented quality from computer tomography data. The prostheses can then be perfectly anchored, and will be held safely in place for longer.

Structure Of TIGAR, A Possible Cancer Flag, Discovered

Two Brown University researchers have determined the three-dimensional structure of an enzyme whose presence in the body could help doctors detect cancer earlier or develop more targeted treatments
Hua Li and Gerwald Jogl detail their progress with the enzyme known as TIGAR in a paper to be published Jan. 16, 2009, in The Journal of Biological Chemistry.

“It will help us to understand where else we should be looking for good [anti-cancer] targets,” said Jogl, assistant professor of biology in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown. Jogl is the study’s principal investigator and corresponding author. Li is a fifth-year Ph.D. student based in Jogl’s lab and is the lead author.

Jogl and Li wanted to determine the structure of TIGAR. After more than a year of research, they discovered that it is has a more substantive active site than they had expected. To map the structure, the pair used a method called X-ray crystallography.

The process involved using intensive X-ray light produced at the National Synchroton Light Source in Brookhaven, N.Y., to analyze crystals grown from samples of the TIGAR enzyme.

A separate study by researchers from St. Jude’s Children’s Research Hospital first identified the existence of TIGAR. Those results were published in CELL in 2006.

TIGAR, which helps regulate energy production in the cell, is activated after cell damage. Because of this, the presence of the enzyme can indicate potential problems that may lead to cancer. But TIGAR itself is positive. Once activated, TIGAR slows all processes in the cell, allowing time to repair cell damage. This process is also intended to prevent further damage that could lead to cancer.

Jogl and Li believe their finding may suggest that TIGAR has additional functions in the cell.

Understanding TIGAR is important, Jogl said, because the enzyme is “one of the good guys” in the battle against cancer. Because its presence can come in tandem with cellular damage, TIGAR is an important clue for scientists that could indicate cancer may follow. Knowing more about TIGAR could lead to earlier cancer detection or even preventative treatments.

“We are looking at the good guys,” Jogl said. “Studying the good guys will lead us to the bad guys and where the places are to interfere.”

A National Institutes of Health grant helped support the study.