The International Conference on Alzheimer's Disease (ICAD), sponsored by the Alzheimer's Association in Chicago in July 2008, attracted more than 5,400 researchers, physicians, and advocates seeking a better understanding of the complex neurodegenerative disorder. Through some 2,000 plenary, symposium, oral, and poster presentations, ICAD offered a forum to explore and advance the science behind Alzheimer's and other types of dementia. NIA, the world's leading funder of AD research, supported much of the work reported at the conference, in areas ranging from drug and non-pharmacological intervention trials and neuroimaging to genetics, basic cellular and molecular research, and social and behavioral issues. Private-sector efforts were presented as well, with several studies built on a foundation laid out by federally supported work.
"ICAD presentations included an array of new drugs in the pipeline that look promising, as well as drugs that have been used for other diseases and disorders. It also included reports on advances in biomarkers and new approaches to the clinical treatment of Alzheimer's," says Dr. Marcelle Morrison-Bogorad, director of NIA's Division of Neuroscience. "But the meeting also highlighted the challenges facing researchers, from fully understanding Alzheimer's basic pathology to designing and conducting clinical trials when physical changes in the brain take place decades before symptoms appear."
Drug investigators continue to target beta-amyloid protein (a protein found in clumps or plaques in the brains of people with AD) in their search for therapies to slow or stop the progression of AD.
- In a pilot clinical trial, intravenous immunoglobulin (IVIg), used for 25 years to treat autoimmune diseases, was found to improve the cognitive health of patients with mild to moderate AD. A phase III clinical trial is testing whether IVIg antibodies can modify the course of mild AD.
The following industry-sponsored trials were reported at ICAD:
- PBT2, a metal-protein-attenuating compound being developed by Prana Biotechnology Ltd., Parkville, Australia, reduced the toxic form of beta-amyloid by preventing its interaction with copper and zinc. Results of a phase IIa clinical trial in people with early-stage AD were similar to the pattern of improvement observed in animal models. PBT2 improved executive function, an important aspect of cognitive performance, in these patients.
New potential drug treatments are aiming at diverse targets, such as tau protein aggregates, which form tangles in the brains of people with AD; the healthy functioning of mitochondria; and the loss of synapses (areas where electrical impulses pass from one neuron to another) in AD patients.
- Dimebon, an antihistamine, stabilized and improved cognitive function in patients with mild to moderate AD, in a 6-month, double-blind, placebo-controlled trial in Russia. At the meeting, results of an open-label extension (where all patients received the active medication) were reported. Patients treated with Dimebon for a total of 18 months continued to show benefit on all measures. Patients originally randomized to placebo and then crossed over to Dimebon treatment had stabilization of their previously documented decline. A phase III clinical trial is now recruiting participants for testing the drug, which is believed to improve mitochondrial function.
- Rember, a novel form of the dye methylthioninium chloride, was found to reduce AD progression for mild- to moderate-AD patients in a phase II trial. The developer, TauRx Therapeutics of Singapore, says that the drug attacks tau, thereby reducing neurofibrillary tangles. A phase III trial awaits FDA approval.
- The peptide AL-108, given by nasal spray, improved some aspects of memory among patients with amnestic mild cognitive impairment (aMCI), in a phase II clinical trial. The compound is designed to combat tau tangles and will now be tested on AD patients. Preclinical testing of this compound was funded by NIA.
- Souvenaid® , a once-a-day, multinutrient drink containing a synergistic combination of active nutrients, was reported to improve memory in patients with early-stage AD. Its development, by Danone Research Centre for Specialized Nutrition, Frampton, United Kingdom, is based on the idea that nutrients increase synapse formation and reduce the production of beta-amyloid. The design for the nutrient-filled drink is based on NIA-funded work conducted by the Massachusetts Institute of Technology.
Some researchers are focused on methods to identify biomarkers (physical characteristics that indicate the presence of a disease or condition)-from simple blood tests to imaging techniques-that may improve diagnosis of AD in its earliest stages and improve treatment.
- A low level of Aß42, a sticky variety of amyloid protein, in cerebrospinal fluid correlates with amyloid in the brain, even in nondemented individuals. These findings eventually may be used to identify preclinical AD at its earliest stages and to improve treatment.
- A new blood test shows that CD-69, a protein involved in white blood cell growth, enabled researchers to differentiate between AD patients and Parkinson's patients with dementia, and between AD patients and those without the disease. A larger study is now underway.
Physical inactivity and mental inactivity are associated with cognitive decline. Now researchers are using imaging and other methods to demonstrate that lifestyle changes and exercise can improve the quality of life for AD patients.
- Researchers using MRI and other neuroimaging techniques found a direct link between the size of the hippocampus of the brain and cardiovascular fitness in early-AD patients. The more fit the AD patient, the larger the hippocampus.
- Metabolic syndrome, a group of heart disease risk factors that includes abdominal obesity, elevated blood pressure, and low HDL cholesterol, may play a role in cognitive decline with age. Older people with the syndrome had an almost 35 percent lower level of cognitive performance than did similarly aged people free of the disorder.
For more information
For more information on ICAD, go to www.alz.org/icad.