When doctors diagnose a person with Alzheimer's disease, they are using criteria adopted in 1984. A lot has changed since then. Now many scientists say after two and a half decades of research into the debilitating disease, the criteria are in need of an extreme makeover.
Much of the impetus for the proposed changes are “recent disappointments in clinical trials” of drugs used to treat the disease once dementia has set in,” said Dr. Reisa Sperling, a neurologist who chaired one of three workgroups convened by the National Institute on Aging and the Alzheimer's Association to develop updated diagnostic criteria.
Recent research has suggested treatment of Alzheimer's needs to begin much earlier, perhaps even before symptoms appear, Sperling said. And for that to happen, Alzheimer's diagnosis must be brought into the 21st century.
In July, Sperling's group, along with two other research teams, announced their proposed updates to the original 1984 diagnostic developed by the National Institute of Neurological Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association.
The new criteria would incorporate what scientists have learned about genes that might predict the development of Alzheimer's, and other biomarkers found in the bodies of people with the disease. They would also strive to disentangle signs of Alzheimer's from those of other dementias, and create ways to recognize additional stages of mild cognitive impairment (MCI), which can be an early sign of Alzheimer's, and other early stages of disease. Research has shown Alzheimer's may begin as many as 20 years before symptoms appear. [What's the Difference Between Alzheimer's and Dementia?]
“We felt it was important to move Alzheimer's disease in this direction, but right now we are proposing these criteria for research. We still have a lot of work to do,” Sperling said.
Marking Alzheimer's development
Genes, including one called apoE, and other biomarkers figure prominently in the proposed criteria, and understandably so: Individuals with the apoE gene, which plays a role in cholesterol transport, are three times as likely to develop Alzheimer's as people without it.
Still, dementia caused by Alzheimer's is not usually inherited. Finding ways to predict who will eventually develop Alzheimer's could lead to earlier and more effective treatments, and perhaps a better prognosis, Sperling said. For those who don't have the apoE gene, other biomarkers could hold clues to the disease's early stages.
For example, some studies have shown levels of a protein called tau in the cerebrospinal fluid (a measurement scientists call CSF tau) can predict with fairly high accuracy future development of Alzheimer's in individuals with mild cognitive impairment. Changes in the protein may also be detectable in those who have no symptoms.
Furthermore, biomarkers could help in Alzheimer's drug development. In a study of biomarkers published in the journal PLoS ONE last summer, a group of Swedish researchers suggested that CSF tau could be measured in patients participating in early drug trials, and was a highly “sensitive tool” that could be used to isolate the most promising therapies that would be worth pursuing in larger, more costly clinical trials.
Differentiating dementia types
By including biomarkers, the diagnostic criteria would be made more objective, but as one scientist wrote on June 25 in the journal Alzheimer's Research & Therapy, “the heterogeneity of [Alzheimer's] disease progression” may provide too complex a target to pin on a single marker.
The proposed updates by Sperling and her colleagues take this into account.
“There are likely many other contributing factors that we do not yet understand,” Sperling said.
One of the goals of the new criteria is to include better descriptions of the types of dementia. This would go a long way toward improving drug development for both Alzheimer's disease and other dementias, such as MCI, for which there are currently no Food and Drug Administration-approved therapies.
MCI shares symptoms with Alzheimer's — memory and language problems, for example — but scientists now understand that it is a distinct type of dementia. A person with MCI can function independently, and may never develop Alzheimer's.
There is also increasing evidence that Alzheimer's disease frequently occurs with dementia that is brought on by problems with the brain's blood vessels. Some studies even suggest that cerebrovascular disease, which can lead to stroke, may influence the buildup of plaques and tangles in the brain and exacerbate Alzheimer's symptoms. New criteria may include these findings, researchers say.
Aging without Alzheimer's
Although the new proposed criteria are based on advances in the scientific understanding of Alzheimer's and not yet rigorously tested, Sperling told MyHealthNewsDaily, “they are absolutely a starting point.”
The proposed criteria have spotlighted the research areas that show promise in improving Alzheimer's diagnosis. Next, they will have to be validated in clinical trials before they are adapted to medical practice. There are still many unknowns.
“We hope that eventually these new criteria will lead to earlier diagnosis and treatment, perhaps even before symptoms are apparent, but that could be as much as 10 years away,” Sperling said.