In the largest cooperative investigation to date among 26 federally-funded Alzheimer’s Disease Centers (ADCs) nationwide, researchers from Columbia University College of Physicians & Surgeons in collaboration with the National Institute on Aging (NIA) have discovered that the ApoE genetic test for Alzheimer’s coupled with a thorough clinical evaluation may help to confirm the diagnosis of the disease. The study reported, in the Feb. 18 issue of The New England Journal of Medicine, emphasizes that results from the ApoE-4 genetic test–which detects the presence of the apolipoprotein E (ApoE) gene in the DNA of a patient’s blood– by itself is inconclusive and does not provide sufficient evidence to diagnose Alzheimer’s disease. Researchers discovered that when the ApoE test is administered along with a thorough examination the validation of the clinical diagnosis of Alzheimer’s disease could be greatly improved. In 1995, the first commercial tests for Alzheimer’s disease risk prompted public health experts to call for more research and special legal protection for individuals’ genetic information. At that time the scientific community reached no consensus on the meaning of a “positive test.” The United States spends more than $100 billion a year caring for people with Alzheimer’s disease. “The apolipoprotein E genotype may be undeniable as a genetic risk factor for Alzheimer’s disease, but its use as a diagnostic aid has received little attention until now,” says Richard Mayeux, M.D., M.S.E., senior author and Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Public Health (epidemiology) at Columbia-Presbyterian. “This study for the first time provides clarification of the usefulness of ApoE testing to help with diagnosis and treatment of Alzheimer’s.” “We cannot underestimate the usefulness of increasing a physician’s confidence in diagnosing a disease of this magnitude,” says Creighton Phelps, M.D., of the National Institutes of Health. “When facing a family who must bear the weight of such devastating news, a majority of doctors would appreciate as many tools as possible to help them in their certainty of diagnosis and based on this research, ApoE testing may be one such tool.” Investigators, led by Dr. Mayeux, reviewed the eligibility of men and women referred to ADCs for diagnosis of dementia. The study examined records of 1,108 women and 1,080 men. Each patient examined had a battery of clinical and behavioral tests, followed by numerous laboratory and brain imaging studies. The patients were followed throughout the course of their disease and their brains were examined upon death. Based on brain autopsies Dr. Mayeux found that 93 percent of the patients who were found to have Alzheimer’s, i.e, their brains showed clear evidence of Alzheimer’s-related changes, had been diagnosed by a physician as having the disease. However, 45 percent of those found to have other forms of dementia at the time of brain autopsy had also been diagnosed by physicians as having Alzheimer’s. This high rate of false positive diagnoses (45 percent) shows the limitations of using recommended clinical criteria alone. Dr. Mayeux and colleagues examined the effect of the ApoE genotype in reducing false positive diagnoses and in adding to the assurance of clinical diagnoses. By using the ApoE genotype only in patients who first met clinical criteria for Alzheimer’s, the false positive rate of diagnosis decreased from 45 percent to 16 percent. The addition of ApoE genotyping to an arsenal of other tests that are used to determine Alzheimer’s status may be useful, but Dr. Mayeux cautions that the study was “done in a selected group of people who receive treatment in specialized centers for Alzheimer’s disease, and that the results do not apply to individuals of other ethnic groups or health care situations. More broad-based study is needed before these results can be assumed to be universally applicable.” Other Columbia authors were Steven Shea, M.D., and Ming-xin Tang, PhD.