New types of tests for Alzheimer’s may improve diagnosis and treatment
Although my grandmother received a diagnosis of Alzheimer’s disease in her 80s, my family was never sure that’s what she had.
She certainly suffered from dementia: She was able to recall childhood memories but couldn’t remember what she had had for lunch. But dementia and Alzheimer’s are not synonymous. Back then, the only way to look for the telltale Alzheimer’s plaques – deposits of the protein fragment beta amyloid that accumulate in the spaces between nerve cells – was through an autopsy, which we didn’t do.
Over the past 15 years, researchers have developed a greater understanding of how the disease works. We now have more accurate ways of diagnosing Alzheimer’s and are moving closer to developing drugs to directly attack the disease. Much of this work is still in the early stages, but experts are growing more hopeful about dealing with the debilitating disease, which currently has no cure.
Now, for example, we no longer have to rely on autopsies to confirm the existence of Alzheimer’s plaques. In a major advance last year, the Food and Drug Administration approved a method that uses a radioactive dye, known commercially as Amyvid, to light up amyloid plaques in a PET scan.
The FDA approved Amyvid to rule out Alzheimer’s when the scan is negative and to confirm the presence of plaques when positive, but that does not necessarily indicate the disease is present. However, some doctors are using the scans to confirm the disease, which experts say is misdiagnosed up to a quarter of the time. Paul Aisen, director of the Alzheimer’s Disease Cooperative Study at University of California at San Diego, calls Amyvid an “enormous advance” because a positive scan, combined with his clinical diagnosis, means he can tell patients and their families the disease is “present, not probable.”
However, the scans are not available everywhere, cost $3,000 to $4,000 and are not covered by Medicare or other insurers.
Still, says John Morris, a neurologist at Washington University School of Medicine in St. Louis, “families want to know.” A few of his patients have paid for the test out of pocket.
Most physicians are using the scans only to help confirm or rule out Alzheimer’s in complex cases. Other imaging tests being developed track another sign of Alzheimer’s in the brain, tangles of a protein called tau. By identifying cases at much earlier stages, such tests may change how experimental treatments for the disease get tested.
All five current Alzheimer’s drugs, including Aricept and Exelon, have limited effectiveness. They treat the symptoms of cognitive impairment by attempting to rebalance the scrambled chemical signals in the brain. But according to the Alzheimer’s Association, they typically stave off cognitive decline for less than a year and only in about half of the patients who take them.
“We have drugs that try to make the brain work better in the face of the disease, but they don’t treat the underlying disease process,” says Reisa Sperling, director of the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital in Boston.
Efforts to make more effective treatments have been challenging. Morris says eight drugs aimed at slowing or removing the buildup of amyloid plaques have failed to pass the clinical trials needed for drug approval in the past 13 years. Those failures probably reflect “too little, too late,” experts say, because the drugs were tested on patients who already exhibited Alzheimer’s dementia, now thought to be the final stage of the disease.
Abnormal accumulation of amyloid is now suspected to begin 10 or even 20 years before cognitive symptoms appear. So researchers and drug companies are shifting their testing to patients who show no signs of the disease but who are likely to develop it. Those patients will be identified either using scans to detect plaque or through genetic screening.
For a trial later this year, Sperling and her team will recruit 1,000 people who exhibit no cognitive dysfunction but whose Amyvid scans show amyloid accumulation. The trial will test whether giving patients an antibody drug called solanezumab, which binds to and mops up the soluble form of amyloid, will slow the onset of cognitive decline.
Along similar lines, Morris and colleagues at the Dominantly Inherited Alzheimer Network, an international research partnership of scientists, will be testing two drugs in the rare set of patients who are genetically predisposed to developing early-onset Alzheimer’s, typically in their mid-40s. This will be the first trial to test whether amyloid-attacking drugs can slow or stop the progression of Alzheimer’s in patients destined to develop it.