Temple Researcher Part of Team That Discovered Blood Test to More Accurately Predict Alzheimer’s Disease Before Onset of Symptoms

It takes a team to forge successful research. An announcement on March 9, 2014, that a simple blood test may detect Alzheimer's disease years before the first symptoms appear was a result of such collaboration. Epidemiologist Susan Fisher, PhD, Chair of the Department of Clinical Sciences at Temple University School of Medicine, played a critical role in designing the study that led to this promising result.
 
Fisher's work emphasized elimination of accidental bias in the study. Working in concert with principal investigators from Georgetown University and the University of Rochester Medical Center, she guided decisions on how to choose trial participants and how to keep them involved through the multi-year study. The results, published in Nature Medicine, have been reported worldwide by major media outlets.
 
"My role was to see where bias could enter the study design and find ways to prevent it," Dr. Fisher explained. "For instance, in this study, we recruited patients from family physician practices. Had we recruited only from neurology practices, the study population would likely have had more cases of Alzheimer's disease. "Such a skewed population would have muddled the research results.
 
Among the many challenges for Alzheimer's researchers is finding a way to detect the disease before its damage has gone too far. Yet typically, patients’ brains are riddled with damage by the time the first overt symptoms appear.
 
Although existing Alzheimer's therapies may limit disease symptoms temporarily, no medication can stop its progress. Part of the problem may be that the drugs come too late in the course of the disease, like a fire crew arriving when the house is already engulfed. If physicians could detect the disease before sparks turn into flames, the hope is that existing and/or new medications could slow and even eventually halt further dramatic damage. But thus far, early diagnosis is impossible. Although several promising studies have suggested potential early detection methods, all so far are expensive, cumbersome, or uncomfortable. And perhaps most important, none is sufficiently accurate.
 
The Nature Medicine paper offers hope of a test that can read the signature of Alzheimer's in the blood before the ink dries. A laboratory test could scan blood samples searching for declining levels of 10 chemicals that indicate damage to nerve cell membranes, which are made of phospholipids. The researchers showed that this 10-phospholipids panel can predict who will develop Alzheimer's nine times out of 10 – a prediction rate better than many standard diagnostic exams in use today. For instance, mammography accurately predicts breast cancer roughly 8 out of 10 times, according to the National Cancer Institute.
 
“We wanted to be able to identify individuals at risk of Alzheimer’s disease, with the long-term goal of being able to develop a therapeutic strategy to prevent, restrict or delay the onset of cognitive deficits associated with this devastating disease,” Dr. Fisher said.

The research team arrived at the 10-metabolite panel by comparing the blood of people who developed Alzheimer's, or a mild cognitive impairment that often leads to Alzheimer's, to those who did not. The researchers recruited 525 people ages 70 and older, collected blood samples, and administered annual cognitive testing. In year three, 74 participants showed signs of cognitive impairment, including 28 who developed the memory problems during the course of the study. The remaining 46 began the study with some form of impairment. By comparing blood samples from those who developed impairment to samples from those who did not, researchers found 10 phospholipids that differed between the two groups.
 
Dr. Fisher says several more studies will be necessary before such a test is proven for use in patients.
 
“The panel needs to be tested in a larger group of subjects and a more diverse group,” she said, noting that the study population was largely middle- to upper-income, college-educated and white. “The results are striking, but we’d like to know if they’re sustainable and can be replicated in a larger sample.”