12.05.16 Mary Yamin-Garone DeMystifying Alzheimer’s
Good afternoon. Welcome to Demystifying Alzheimer’s. I’m your hostess Mary Yamin-Garone.
Today’s topic is “More about Treatments on the Horizon.”
With the number of people living with Alzheimer’s expected to almost triple by 2050, the race is on to find a treatment that will prevent or slow the disease. Unfortunately, Alzheimer’s investigations are hampered by a lack of sophisticated diagnostic tests that can detect the disease in its early stages. Without these tools, Lewy body and vascular dementia may be misdiagnosed as Alzheimer’s.
AD is currently diagnosed based on symptoms, cognitive testing and a process of elimination—imprecise and relatively unsophisticated methods that may miss early signs of dementia. As a result, detecting and treating the disease are delayed until after irreversible damage has been done.
Researchers are searching for new ways of identifying individuals who are at risk for Alzheimer’s while they’re still cognitively normal. In doing so, they can steer them toward trials and treatments and develop new therapies that help preserve brain function. Brain changes that occur with AD, including amyloid plaques and neurofibrillary tangles, begin developing years before abnormal clinical symptoms, such as memory loss, develop.
Development of increasingly sensitive, sophisticated imaging techniques has yielded encouraging results. Alzheimer’s scientists have trained energy and attention on using these technologies with biomarkers—a feature or facet present in the body that can be used to measure the progress of disease or the effects of treatment. Researchers hope these advances will lead to diagnostic tests that can help detect Alzheimer’s before its symptoms appear and evaluate early interventions.
Scientists have already developed magnetic resonance imaging (MRI) and positron emission tomography (PET) scans that can identify and measure shrinkage and other signs of Alzheimer’s symptoms in the brain. Using PET scanners, scientists can now “image” beta-amyloid plaque deposits in the brains of individuals who have been injected with a radioactive compound or tracer. The tracer attaches to amyloid, which “lights up” when it’s imaged in a PET scan of the brain. Other researchers are using computer analyses of MRI scans to assess the severity of AD-related neurofibrillary tangles.
Researchers note that identifying biomarkers from blood or urine samples should result in developing simple blood tests that could be useful in detecting Alzheimer’s, measuring brain damage and evaluating the effectiveness of therapies during clinical trials. Some noninvasive tests are being developed and some research scientists are hopeful that presymptomatic biomarkers can be used as “surrogates” for Alzheimer’s to measure the effect of drugs on disease progression in clinical trials.
Because Alzheimer’s progresses so slowly, it’s often difficult to gauge the effectiveness of experimental drugs in Phase II clinical trials, which typically last no longer than 18 months. Alzheimer’s symptoms can’t be readily diagnosed, making it difficult for researchers to determine if the drug has some real effect in studies that last less than two years. If a biomarker could somehow measure clinical efficacy, research teams would know better which treatments should proceed to Phase III clinical trials.
Some knowledgeable observers of Alzheimer’s scientists, however, question how useful biomarkers will be in clinical research in the future. After all, no biomarker can predict or diagnose AD with scientific accuracy. In addition, neuroimaging studies suggesting that the presence or absence of amyloid plaques in the brain doesn’t necessarily correspond with cognitive impairment call into question how valuable the diagnostics that detect amyloid plaques are.
Other researchers are focusing on moving the detection threshold for Alzheimer’s to earlier stages by studying the earliest form of detectable dementia: mild cognitive impairment (MCI). Not everyone with MCI develops AD but the condition is regarded as a significant risk factor. The ranks of those diagnosed with mild cognitive impairment, which is already large, are growing.
Studies show that certain medications prescribed to treat other conditions may affect Alzheimer’s symptoms. In one study, AD patients who had diabetes and took insulin and another anti-diabetes medication to control blood sugar had 80 percent fewer amyloid plaques. Researchers speculated that the drugs might normalize the brain’s communication network of insulin receptors, which goes awry in those with Alzheimer’s while clearing away the damaging plaques in the brain.
Scientists are proceeding apace on gene research that may lead to clues about the cause and effective treatments of Alzheimer’s. In the future, as researchers learn more about the human genome, they expect to find up to a dozen genetic abnormalities that predispose some individuals to late-onset Alzheimer’s.
The ApoE gene codes for a protein that helps carry cholesterol in the bloodstream. According to the National Institutes of Aging, scientists believe learning more about the role it plays and other risk factor genes in the development of Alzheimer’s may help identify who would benefit from prevention and treatment efforts. The agency launched a major study to discover any remaining genetic risk factors for late-onset Alzheimer’s. Geneticists from the institute’s Alzheimer’s Disease Centers are working to collect genetic samples from families affected by multiple cases of late-onset AD.
A blood test can identify which ApoE alleles an individual carries. Because the ApoE gene is only a risk factor for Alzheimer’s, the test can’t tell with any certainty who will develop AD. Not everyone with the gene develops Alzheimer’s nor does everyone with the disease carry a copy of the ApoE4 variation. In some cases, ApoE testing is used in conjunction with other medical tests to strengthen the diagnosis of a suspected case of AD.
The NIA warns that ApoE testing raises ethical, legal and social questions. Confidentiality laws protect information gathered for research purposes. The information, however, may not remain confidential if it becomes part of a person’s medical records. After that, employers, insurance companies and other healthcare organizations could obtain genetic test results and use them to discriminate againt job seekers, employees and those seeking insurance coverage.
Scientists believe that understanding more about the genetic bases of Alzheimer’s will help them better understand the mechanisms of the disease, such as how it begins and why some people with memory problems develop AD while others don’t. They’re eager to learn how Alzheimer’s risk factor genes interact with environmental and lifestyle factors to influence individual AD risk.
That’s all for today. Thanks for listening. I hope this information was helpful.
Join me next time for more Demystifying Alzheimer’s.