Funded Programs Clinical

Clinical Interpretation of MRI to Predict Conversion of Mild Cognitive Impairment to Dementia Investigator(s): Charles DeCarli Institution(s): University of California, Davis, CA

Summary:
Currently, there is no simple test for the diagnosis of Alzheimer’s disease which can be difficult to diagnose clinically, particularly when symptoms are very mild. Many clinicians believe that the lack of simple tools to assist physicians in early diagnosis of AD leads to delayed diagnosis and treatment of this disorder despite accruing evidence that early treatment with currently licensed medications are beneficial. A number of clinical factors have been shown to significantly predict conversion of mild cognitive impairment (MCI) to dementia. To date, the two strongest predictors are cognitive status and hippocampal volumes. Unfortunately, each of these tests is time consuming to perform, expensive, and generally not available to the average clinician making the diagnosis of dementia. In this program, Dr. DeCarli will compare simple clinical MRI ratings of hippocampus done by treating physicians to more sophisticated, but time consuming and expensive quantitative MRI measures, as well as neuropsychological testing, that is available through the Alzheimer’s Disease Cooperative Study (ADCS) clinical trial: “A Randomized, Double Blind, Placebo-Controlled Trial of Vitamin E and Donepezil HCL to Delay Clinical Progression from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD).”

Phase I Pilot Study of Combination Antioxidants in Aging Investigator(s): Carl Cotman, PhD Institution(s): University of California Irvine, Irvine, CA

Summary:
Oxidative damage has been implicated in aging and dementia. Some laboratory and clinical studies suggest that individual antioxidants (such as vitamin E) may be therapeutic for the treatment of Alzheimer’s disease. The dietary administration of a combination of antioxidants could prove more effective than individual antioxidants alone. However, the benefit of a combination of antioxidants has not been evaluated in clinical trials. The aim of this program is a Phase I trial to obtain safety and preliminary efficacy data with regard to cognitive outcomes employing the combination of antioxidants vitamins E, C and lipoic acid. These antioxidants were chosen because they each attack a different component of oxidation. For example, vitamin E is a lipid soluble antioxidant and would target fatty compartments such as cell membranes, while vitamin C is a water- soluble vitamin and works in the interior of cells. Lipoic acid is thought to target oxidative processes in the mitochondria (the energy machinery of the cell). This clinical trial will be one of the first to obtain data on the safety and efficacy of a scientifically rational combination of antioxidants for improving cognitive function in normal older persons. If successful the clinical trial will lead to a much larger prevention trial to be funded by the NIH.

Human Anti-Ab Antibodies for the Treatment of Alzheimer’s Disease Investigator(s): Marc E. Weksler, MD Institution(s): Weil Medical College of Cornell University, New York, NY

Summary:
Immunization with beta-amyloid peptides has been recently been shown to be dramatically effective at reducing brain amyloid in preclinical studies. This has raised the possibility of a role for the immune system in Alzheimer’s disease and suggested the therapeutic potential of a vaccine for AD. Based on these studies, some scientists have postulated that AD may be the result of an immune deficiency with lowered levels of natural serum antibodies to beta-amyloid possibly accelerating the aggregation of beta-amyloid in brain. Preliminary data from Dr. Weksler’s lab suggests that AD patients have lower levels of serum anti-amyloid antibodies than elderly, non-demented control subjects. These data suggest that lowered levels of anti-amyloid antibodies are a risk factor for AD and have prompted Dr. Weksler to propose further longitudinal studies investigating the levels of circulating anti-amyloid antibodies in AD. The aim of this program is to confirm that patients with AD have low levels of circulating serum anti-beta amyloid antibodies. A subsidiary aim is to determine, by longitudinal analysis, if in AD patients lowered levels of circulating anti-amyloid antibodies precede or develop after the onset of symptomatic AD and are therefore a risk factor for AD. This program may result in a new diagnostic marker for AD that measures circulating anti-amyloid antibodies.