How to Solve Three Puzzles

Another technology in limited clinical use is fluorodeoxyglucose positron emission tomography (FDG-PET). Images produced by FDG-PET reveal patterns of glucose metabolism in the cerebral cortex, the site of abstract thought, reasoning and learning. Because active neurons guzzle glucose for energy, diminished uptake in a specific pattern can denote Alzheimer's. In the research setting, scientists have even used FDG-PET to identify people who do not yet have Alzheimer's but are at risk for developing it, or for developing mild cognitive impairment.

A different kind of PET-scan technology builds on recent discoveries about amyloid plaques and tau tangles, the neuron-killing proteins that accumulate in the brains of Alzheimer's patients. Researchers at the University of Pittsburgh have developed Pittsburgh Compound-B, or PIB. When injected into the blood, this compound binds to amyloid plaques in the brain, allowing them to be detected on PET scans. PET scans with PIB clearly distinguish people with Alzheimer's from healthy people. They may also help identify people with the progressive form of MCI.

Taking a different approach, other researchers are identifying early changes in the levels of particular brain proteins in cerebrospinal fluid. (The clear spinal fluid constantly bathes the brain and spinal cord.) Spinal-fluid levels of the protein tau are typically elevated in Alzheimer's, and an altered version of the tau protein, known as phosphorylated tau, can be detected early in Alzheimer's. Lowered spinal-fluid concentrations of an altered version of beta-amyloid, called Aß42, are typical in Alzheimer's and can also help identify people with mild cognitive impairment who are most likely to progress to Alzheimer's.

Although all these new imaging and biochemical developments are individually promising, the combination of several different imaging tests and biochemical markers may yield the most accurate diagnosis. For example, scientists at the New York University School of Medicine have reported that combining volumetric MRI of the hippocampus with spinal-fluid measures of phosphorylated tau and isoprostane—a marker of oxidative stress—improved diagnostic accuracy in identifying people with mild cognitive impairment who are most likely to progress to Alzheimer's.

We may never reach the stage where we have a single, highly accurate blood test for Alzheimer's, as we do for diabetes. But as the diagnostic technology improves, it may be possible to diagnose Alzheimer's long before symptoms appear. And if the disease-modifying drugs work as intended, that will be very good news indeed.
--John H. Growdon, M.D., founding Director of the Massachusetts Alzheimer's Disease Research Center at Massachusetts General Hospital and Professor Of Neurology at Harvard Medical School, and Ann MacDonald, Editor of the Harvard Mental Health Letter

Heart Disease in Women
When it comes to diagnosing the most common kind of heart disease, some cardiologists share Henry Higgins's lament in "My Fair Lady": "Why can't a woman be more like a man?" That's because many women don't have the typical symptoms, like crushing chest pain and shortness of breath brought on by physical activity or stress. Instead, they have diffuse discomfort in the chest, unusual exhaustion or depression without an apparent reason. To make matters worse, the tests considered best at diagnosing coronary-artery disease generally don't work as well for women as they do for men. As a result, an alarming number of women with heart disease go undiagnosed and untreated despite repeated visits to the doctor and the emergency room.