Doctors identified a type of dementia that may be more common than Alzheimer's disease, according to a report published Tuesday in the journal Brain. Here's why some experts are calling this "the most important dementia finding in years," according to Michelle Roberts in the BBC.
How do we know who has Alzheimer's?
In general, age-related diseases and forms of dementia are caused by "proteinaceous glop[s]," or misfolded proteins that clog up nerve cells and the spaces between them, according to Peter Nelson, a professor of pathology at the University of Kentucky and lead author of the report. "Proteins always get folded, but when they misfold, [it] produces toxic effects because the protein is impaired from its normal activities," he said.
When patients show signs of dementia, many doctors assume that Alzheimer's is the cause. Alzheimer's currently is considered the most common cause of dementia, accounting for 60-80% of all cases. The type of protein that becomes misfolded indicates the type of dementia. For example, patients with Alzheimer's typically have plaques and tangles between their nerve cells that are caused by the buildup of the proteins amyloid beta and tau, respectively.
But researchers have long known that not all patients exhibiting dementia symptoms have those hallmark biomarkers of Alzheimer's in their brain.
"All over the world we saw very old people who had deterioration of their faculties and dementia, but no plaques and tangles," Nelson said.
Therefore, researchers have been searching for other biological reasons why patients develop dementia symptoms. This new study offers a promising new alternative.
Researchers find alternative dementia diagnosis
The international team of researchers found another protein called TDP-43, which can begin to fold incorrectly in the brains of older patients and cause a disease researchers named limbic-predominant age-related TDP-43 encephalopathy (LATE).
According to the researchers, LATE develops more slowly than Alzheimer's and seems to appear later, when patients are in their 80s and 90s. TDP also seems to accumulate in a different part of the brain than the proteins involved in Alzheimer's. "TDP-43 likes certain parts of the brain that the Alzheimer's pathology is less enamored of," said Sandra Weintraub, a professor at Northwestern University Feinberg School of Medicine, who was not involved in the report.
The TDP protein just connected to LATE has also been associated with several other diseases, including ALS, Lou Gehrig's and another type of dementia, frontotemporal lobular degeneration. However, LATE "is a disease that's 100 times more common than [any] of those, and nobody knows about it," said Nelson.
The researchers estimated that LATE is actually one of the most common types of dementia. According to the paper, between 20 and 50% of people over 80 will have brain changes due to LATE—and that prevalence increases as people age. They noted that LATE and Alzheimer's are often found together in patients, and may cause a worse cognitive decline than either disease by itself. The researchers estimated that one million Americans have LATE, including one-third of people with Alzheimer's.
Is LATE behind failed Alzheimer's studies?
According to experts, unidentified cases of LATE could explain why some "promising" Alzheimer's drugs failed in clinical trials, NBC News reports. If, for example, 40% of participants in a clinical trial for an Alzheimer's drug actually had LATE, "the study failed because it enrolled the wrong patients," said Richard Isaacson, director of the Alzheimer's Prevention Clinic at NewYork-Presbyterian and Weill Cornell Medicine.
Nelson mentioned the example of one colleague who saw this happen firsthand. Their patient developed dementia after taking part in the Alzheimer's drug trial, "but it turns out he didn't have Alzheimer's disease," Nelson said. "He had LATE." If researchers hope to eventually develop a treatment for Alzheimer's, what they "really need to do is go forward and try to get these people out of the Alzheimer's clinical trials—and instead get them into their own clinical trials," Nelson said.
However, Nina Silverberg, director of the Alzheimer's Disease Research Centers Program at the National Institute on Aging, said cases like the one Nelson described are probably rare. According to Silverberg, most of the patients who participate in Alzheimer's studies are too young to have LATE. "I'm sure it plays some part [in the failures], but maybe not as much as one might think at first," she said.
Finding a treatment for LATE
But before researchers can separate LATE and Alzheimer's patients into distinct clinical trials, they first must find a biomarker to detect the disease. Right now, the only way to identify LATE is post-mortem through autopsies.
"There is a lot of work to be done," Nelson said, adding that the report "is more of a starting point than a finish point."
But while the report won't advance treatment for the disease immediately, it "gives scientists a common language to discuss it," said Nelson. It also unifies other studies that had found hints of LATE or other causes of dementia.
"People have … found different parts of the elephant. But this is the first place where everybody gets together and says, 'This is the whole elephant,'" he said (Carroll, NBC News, 5/1; Roberts, BBC News, 4/30; Nedelman, CNN, 4/30; Chakradarhar, "Morning Rounds," STAT News, 5/1).
Five strategies to build a financially successful memory disorders program
Over 5.3 million Americans currently suffer from Alzheimer's disease and related memory disorders and the number is rising. On top of increased demand, reimbursement processes fail to meet the complex needs of these patients who require multifaceted care.
Here are the five key strategies that a program of any scope and size can implement to provide cost-efficient Alzheimer's and dementia care.