More than 4,000 scientists from around the world have assembled in Washington DC this week to share their latest findings on Alzheimer s disease (AD). While the odds of finding effective treatments remain bleak, at least for the near term, some early studies are now giving us some hope. These studies are the essential framework for finally making some real progress in stymying, or at least impeding the onslaught of this dreadful disease. As populations around the globe age, the urgency of finding a treatment that either prevents, slows the progression, or even cures AD becomes more imperative. While many forms of heart disease (America s #1 killer) and cancer (#2) are treatable, and even preventable, such is not the case with AD. Once symptoms begin, the future is now set in stone. The only unknown is the time-frame, which is subject to some variability. According to the Alzheimer s Association, 5.3 million Americans have the disease, including 200,000 people under the age of 65. "Barring the development of medical breakthroughs, the number will rise to 13.8 million by 2050," the association says in its annual report with two-thirds being women.
It is hoped that presentations at The Alzheimer s Association International Conference (AAIC), which runs through July 23rd, will highlight real advances in this field. Noninvasive diagnostic tools that would allow doctors to determine the degree of progression that will later lead to cognitive impairment, memory lapses and other symptoms of dementia is a crucially-important step towards such breakthroughs. This is because, in the absence of a large cohort of high-risk patients those who have a well-above-average likelihood of developing cognitive impairment upon whom to test and study potential remedies, none will be possible, since the subsequent testing of potential AD drugs on a random population that contains a mix of people who will or will not be likely to develop AD would be akin to throwing darts in the dark.
Researchers and drug companies are keenly interested in biological markers of Alzheimer s that can predict who may develop the progressive memory disease, long before clinical symptoms show up. In recent years, it has become increasingly evident that Alzheimer s-related changes in the brain begin at least 15 years or more before people show signs of detectable memory loss.
Studies of biomarkers of AD blood, spinal fluid (CSF) and/or imaging tests surrogate tests that reliably predict cognitive changes, have been the subject of multiple studies. One was presented on the conference s opening day: Dr. Marilyn Albert, director of the Alzheimer s Disease Research Center at Johns Hopkins School of Medicine, presented results from one of the largest and longest studies of cognitively normal individuals. One study, called Biocard, which began in 1995, followed 189 people for an average of eight years. All the individuals began the study without memory problems, but three-quarters had family members who developed Alzheimer s at some point in their lives. During the follow up period, 60 participants went on to develop either mild cognitive impairment or Alzheimer s.
The study design was not trivial. The participants completed a battery of memory tests and brain scans, and also had samples of CSF tested at various points over the years. No single biomarker alone was sufficient to predict an individual s risk of progression, so the research team set out to determine if a combination of factors might be predictive. Using statistical analysis, the team determined that an algorithm of six biomarkers taken together did, in fact, predict the likelihood that an individual would progress to Alzheimer s.
The six measures in the algorithm included a genetic assessment of whether an individual had a variant of the ApoE4 gene, two memory tests, the level of a protein called tau found in the cerebrospinal fluid and MRI measurements of two brain regions. Of the people who were predicted by biomarker analysis to go on to develop abnormal memory problems, 80% of them did just that. This is a very impressive result. The algorithm also correctly predicted who would not develop memory problems, 75 percent of the time also an impressive number.
In another study, researchers at the University of Alberta, Canada, reported on efforts to test saliva for early biomarkers of cognitive decline. It is not yet clear whether biomarkers of AD in human saliva will be predictive for the development of Alzheimer's Disease, but such a test, if the results pan out would be very simple compared to current methodology.
The study's authors evaluated saliva specimens from 108 individuals who were participating in a study of human aging. The patients were then divided into three groups -- those who aged normally, those with mild cognitive impairment and those with Alzheimer's. Particular substances in the latter two groups could one day be used to point to worse memory performance, researchers speculate. Researchers who discovered the biomarkers say that the potential test, which could take years to develop, could potentially provide another tool to predict future development of mild cognitive impairment and Alzheimer's in cognitively intact individuals.
While in a few years, who knows, some of these preliminary studies may be cited as the origin of the fruitful line of research that, eventually, led to the solution to the horrific AD problem, these studies discussed thus far OK, only two days in don t sound like the first signs of anything miraculous. But the journey of 1,000 miles begins with the first step, wise people have said. We can only hope that the answer or at least an answer comes in our lifetimes and those of our loved ones.
