Clinical Research in Alzheimer’s Disease

By age 85, nearly 50 percent of Americans will suffer from Alzheimer’s disease (AD), according to the Alzheimer’s Association. As a result, there is an urgent need to develop translational research, which will move discoveries made in the laboratory swiftly to the patient’s bedside. Currently, scientists at the Alzheimer’s Disease Research Center (ADRC) at Mount Sinai are involved in several clinical trials that may hold promise for the early diagnosis and treatment of this debilitating neurological disorder.

Early Diagnosis of Alzheimer’s Disease: Biomarker Studies

The majority of patients who are diagnosed with AD have already begun to experience symptoms such as memory loss, behavioral changes, and disorientation. Under the direction of Mary Sano, PhD, Professor of Psychiatry, Associate Dean for Clinical Research, and Director of the ADRC, researchers are developing ways to diagnose AD before these symptoms even occur. Patients who are diagnosed early would be able to start treatment before cognitive impairment occurs.

To identify AD early on, scientists are focusing on biological markers, also known as biomarkers, which help detect pathology and measure the severity of the disease. Such biomarkers include proteins found in the blood and cerebral spinal fluid as well as changes in the brain as seen with neuroimaging techniques such as MRI and PET scans.

“Mount Sinai is the first place in New York City to provide for clinical use, the pioneering FDA-approved technology that allows us to image the toxic amyloid building up in the brain when early-stage patients are transitioning from health to cognitive loss,” says Dr. Sano. “If we can prevent this step, we may be able to stave off Alzheimer’s entirely.”

The new technique uses a radioactive agent called florbetapir (Amyvid), which is administered by injection into the arm. Florbetapir binds to amyloid plaques in the brain, allowing the plaques to be seen on a PET scan. Amyloid plaques are the hallmark pathology in the brains of those with AD. A negative scan indicates the absence of plaques and a low likelihood of AD, while a positive scan indicates plaques are likely to be present and points to a possible diagnosis of AD in patients with cognitive problems.

The goal of the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2), led by Hillel Grossman, MD, Associate Professor of Psychiatry and Co-Director of the ADRC Clinical Core, is to determine whether imaging of the brain through MRI, PET, and amyloid scans can help predict and monitor the onset and progression of AD. In addition to neuroimaging, he will collect and test blood and cerebral spinal fluid to determine if biomarkers can predict and monitor the disease. His research is sponsored by the National Institutes of Health and is taking place at approximately 50 major universities across the U.S. and Canada.

The Role of Nutritional Substances in Alzheimer’s Disease

Nutraceutical, a term that combines the idea of nutrition and pharmaceutical, is used to describe products that treat or prevent disease and are generally regarded as safe by the Food and Drug Administration (FDA). Even though the FDA does not formally recognize this term, many of these products, which can be formulated as pills or other medicinal formulations, are developed the same way as drugs and go through clinical trials to demonstrate their efficacy. Scientists at the ADRC are conducting rigorous studies to assess the effectiveness of several nutraceuticals including resveratrol, NIC5-15, and grape seed extract. When these substances are used in clinical trials, researchers carefully control the dosing and preparation of the product.

“Certain natural compounds have been found to have an effect on the neurochemistry in the brain that is associated with the progression of Alzheimer’s disease,” says Dr. Sano. “Our goal is to evaluate these substances and determine their efficacy for having preventative or therapeutic effects in AD.”

Resveratrol Research Study

Led by Judith Neugroschl, MD, Assistant Professor of Psychiatry and Co-Director of the ADRC Education Core, this study will evaluate the safety, tolerability, and effectiveness of resveratrol— an anti-oxidant found in red grape skins—in people with AD. Researchers are studying the effects of resveratrol, which is thought to have several mechanisms of action related to the development of AD, on memory and thinking. They are also measuring cerebrospinal fluid and blood biomarkers. In this study, groups of individuals with AD will be given either resveratrol or a placebo for one year to determine which group does better over time.

NIC5-15 Clinical Trial

Scientists are studying the effects of NIC5-15, a natural product found in legumes and soybeans, on veterans and non-veterans with AD at the Bronx James J. Peters Veterans Medical Center. In laboratory studies, NIC5-15 has been found to interfere with the accumulation of a protein in the brain that is involved in the development of AD. Dr. Grossman, who is Principal Investigator, hypothesizes NIC5-15 may slow down the progression of the disease. Study participants will receive either NIC5-15 or a placebo for eight months and will be evaluated with physical exams, neurological exams, blood tests, and tests of memory and thinking skills.

Grape Seed Research Study

Dr. Grossman is also leading a study to determine if the antioxidants found in grape seed extract could prevent amyloid beta peptide, which is known to cause neurotoxicity associated with AD. Previous studies by Giulio Maria Pasinetti, MD, PhD, Professor of Neurology, Psychiatry, Neuroscience, and Geriatrics and Palliative Medicine, have shown that administering grape seed extract to mice resulted in lower levels of an amyloid beta oligomer, which had been associated with cognitive decline in mice. The ADRC is a comprehensive research and clinical facility that provides diagnostic evaluations for those with memory complaints and an opportunity to participate in cutting-edge clinical research. For more information or to schedule an appointment, call 212-241-0438.