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Earlier Down Syndrome Screening Bests Second Trimester Tests

A combination of screening tests performed at 11 weeks into pregnancy is better at predicting Down syndrome than more commonly used blood tests during the second trimester, according to one of the largest obstetrical studies ever conducted, in which Columbia University Medical Center played a role.

"These results will undoubtedly change national practice – all pregnant women should have the option of early screening for Down syndrome in their first trimester," says the study's principal investigator, Mary E. D'Alton, M.D., chair of obstetrics and gynecology.

The study of 38,000 women at 15 U.S. hospitals found that the first trimester screening tests identified 87 percent of Down pregnancies while the standard second trimester screening tests detected 81 percent. Both protocols had a 5 percent false positive rate. Complete findings were published in the Nov. 10 issue of the New England Journal of Medicine.

The first trimester screening protocol involves a blood test and an ultrasound exam that measures nuchal translucency, a clear space at the back of the neck that tends to be larger in fetuses with Down syndrome. Because the exam is technically challenging, only professionals who have been trained and certified in the technique should perform it. Information about training can be found at the Maternal-Fetal Medicine Foundation Web Site at

The trial was supported by the NIH and the National Institute of Child Health and Human Development.

Stroke Prevention Procedure May Raise Cognitive Risk

Investigators at Columbia, have found that people who carry the ApoE4 allele – a form of the APOE gene associated with greater Alzheimer's risk – are 62 times more likely than others to develop subtle cognitive problems after a common procedure to prevent stroke.

The huge difference raises questions about whether some ApoE4 carriers should undergo the surgery, carotid endarterectomy (CEA), which removes plaque from arteries that supply blood to the brain.

CEA clearly reduces the risk of stroke in patients whose carotid arteries are more than 70 percent blocked with plaque. But surgeons also perform CEA in some with smaller blockages for whom the benefits are less certain. Adding to the debate about borderline cases, up to 25 percent of patients develop subtle cognitive deficits after surgery.

To help predict which patients are likely to suffer cognitive problems Columbia researchers led by Eric Heyer, M.D., Ph.D., professor of clinical anesthesiology and neurology, and E. Sander Connolly, M.D., associate professor of neurology and neurological surgery, looked for genetic risk factors in 75 patients who underwent CEA. They found that only ApoE4 conferred any risk: 42 percent of the patients with ApoE4 performed worse on cognitive tests compared to only 5 percent of other patients. The findings were published in the December issue of Neurology.

"Some asymptomatic patients with significant carotid artery stenosis and ApoE4 may have to consider the possibility that they may develop cognitive dysfunction as a result of surgery even though a more significant stroke has been averted," says Dr. Heyer, the study's lead author. Genetic testing for the ApoE4 allele is not available now in a clinical setting.

Drs. Heyer and Connolly are now conducting studies to determine whether stenting, an alternative to CEA, results in the same degree of cognitive decline in ApoE4- positive patients.

The study was supported in part by the Irving Center for Clinical Research and the NIH.

Female Athletes Advised of ACL Damage Risk

A study of 123 teenage soccer players has found that changes in muscle strength during puberty may increase a female athlete's risk of tearing the knee's anterior cruciate ligament (ACL).

Female athletes – particularly those who play sports like soccer that involve quick changes in direction – injure the ACL two to eight times more often than males.

Several reasons for women's higher risk have been suggested, including anatomical differences such as wider hips and estrogen's effects on the ACL. These factors, however, cannot be changed to help prevent injury.

Recently, researchers have focused on muscular differences and have found that female athletes tend to have a high quadriceps-to-hamstring strength ratio. Studies suggest that a high ratio puts more stress on the ligament, but that lowering the ratio by increasing hamstring strength reduces ACL injuries in female athletes.

Young female athletes doing leg-strengthening exercises that reduce the risk of ACL injury.

The question remained, when should female athletes begin exercises to reduce ACL injury risk?

Christopher Ahmad, M.D., assistant professor of orthopaedic surgery, and his colleagues in the Center for Shoulder, Elbow, and Sports Medicine at Columbia measured muscle strength in 53 female and 70 male soccer players ranging in age from 10 to 18 and found that the quadriceps-to-hamstring ratio was significantly greater in female players after menarche than in pre-menarche girls, and boys of all ages.

The findings, to be published in the American Journal of Sports Medicine, suggest that female athletes should begin hamstring strength training soon after the onset of menstruation.

Delusions Hasten Alzheimer's Decline

Delusions and hallucinations are common among patients with Alzheimer's disease but findings conflict about whether these symptoms signal a more rapid decline or not.

Now one of the largest such studies, led by CUMC neurologists, has found that delusions or hallucinations are associated with a quicker cognitive and functional decline and earlier institutionalization. The study followed 456 patients from the early stages of Alzheimer's disease for up to 14 years.

They also found for the first time that hallucinations in Alzheimer's are associated with earlier mortality. Presence of hallucinations was associated with about a 1.5 times higher chance of dying during follow-up.

"These results are important because they give patients, family members, and practitioners prognostic information about patients' future disease course," says the study's lead author, Nikolaos Scarmeas, M.D., M.Sc., assistant professor of neurology. The results were published in the October Archives of Neurology.

The research was supported by the NIH and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain.

Chromosome Deletion Increases Schizophrenia Risk

The schizophrenia rate in the general population is about 1 percent, but for people born without a small section of chromosome 22, called 22q11, the risk is strikingly higher. Up to a third develops schizophrenia later in adolescence or early adulthood, making the deletion the disease's greatest known risk factor.

New findings from Joseph Gogos, M.D., Ph.D., assistant professor of physiology and cellular biophysics, and Maria Karayiorgou of Rockefeller University published in the November issue of Nature Neuroscience show that an interaction between two genes within the deletion may explain the risk.

One of these genes – proline dehydrogenase (PRODH) – was first identified by the same researchers as a schizophrenia susceptibility gene three years ago. In the new study, the researchers collaborated to model the effect of altering the expression of PRODH and identify other genes that would impact on its function. They found that mice deficient in this gene share some similarities with schizophrenia patients, including deficits in learning and memory and increased susceptibility to the disorganizing effects of amphetamine.

The researchers also discovered that another gene compensated for the lack of PRODH. When PRODH activity was low, levels of catechol-O-methyltransferase (COMT) increased and reduced the schizophrenia-like behaviors in the PRODH-deficient mice. By contrast, when researchers inhibited COMT, the schizophrenia-like behaviors worsened.

"The fascinating thing is that COMT is also located in the 22q11 region, so the study shows why the disease risk associated with the deletion is so high," Dr. Gogos says. "Patients with the deletion are unable to compensate for their PRODH deficiency by upregulating COMT since they are missing one copy of their COMT gene as well."

The research was supported by the NIH and the New York Academy of Sciences.