The disease, called LATE, can often mirror the symptoms of Alzheimer's disease, although it affects the brain differently and develops more slowly than Alzheimer's disease. Doctors say the two are often found together, and in such cases can lead to a sharper cognitive decline than by itself.
In developing its report, the international team of authors hopes to stimulate research – and perhaps one day, treatments – for a disease that tends to affect people over 80 and "has a growing, but little recognized, impact on public health, "according to the paper.
"We are really reshaping the concept of what dementia is," said lead author Dr. Peter Nelson, director of neuropathology at the University of Kentucky Medical Center.
"There will not be a single disease that is causing all forms of dementia," said Sandra Weintraub, a professor of psychiatry, behavioral science and neurology at Feinberg School of Medicine at Northwestern University. She was not involved in the new article.
Weintraub said that researchers are well aware of the "heterogeneity of dementia," but figuring out exactly why each type may seem so different has been a challenge. Why do some people lose memory first, while others lose their language or have personality changes? Why do some develop dementia earlier in life, while others develop later?
Experts say that this heterogeneity has complicated research into dementia, including Alzheimer's disease, because it was not always clear what the main cause was – and therefore whether doctors were treating the right thing.
What is it?
LATE stands for age-related TDP-43 encephalopathy, predominant in the limbic range. The full name refers to the area of the brain most likely to be affected, as well as protein at the center of everything.
"These age-related dementia diseases are often associated with protein glace," Nelson said. "But different proteins can contribute to the glop."
In Alzheimer's disease, you will find a set of glops. In the dementia of Lewy's body, another glop.
And in the late afternoon, glop is a protein called TDP-43. Doctors are not sure why protein is found in a modified and folded form in a disease such as LATE.
"This is an area that will really be huge in the future. What are the individual vulnerabilities that cause proteins to go to particular regions of the brain?" she said. "It's not just what the protein abnormality is, but where it is."
For more than a decade, physicians have for the first time linked the TDP protein to amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease. He was also linked to another type of dementia, called frontotemporal lobar degeneration.
LATE "is a disease 100 times more common than any of them, and no one knows that," Nelson said.
The new study estimates, based on autopsy studies, that between 20 and 50% of people over 80 will have brain changes associated with LATE. And this prevalence increases with age.
Experts say finding such numbers – as well as finding better ways to detect and research the disease – is what they expect to come out of consensus statements like the new document, which gives scientists a common language to discuss it, according to Nelson.
"People, in their own separate bailiwicks, have found different parts of the elephant," he said. "But this is the first place where everyone gathers and says," This is the whole elephant. "
What can this mean for Alzheimer's disease?
The new guidelines may also have an impact on Alzheimer's research. On the one hand, experts say that some high profile drug tests may have suffered as a result of some patients with unidentified delay – and therefore not responding to treatment.
In fact, Nelson's colleagues recently saw this firsthand: a now deceased patient who was part of an Alzheimer's drug test but developed dementia anyway.
"So the clinical trial was a failure for Alzheimer's disease," Nelson said, "but it turns out he did not have Alzheimer's. He was late."
"I'm sure he plays some role, but maybe not as much as you might think at first," said Silverberg, who co-chaired the working group that led to the new article.
The advances in the tests had already shown that some patients in those studies did not have "the telltale signs of Alzheimer's disease," she said.
In some cases, maybe it was AFTERNOON – "and it is certainly possible that there are other pathologies, as yet undiscovered, that people may have," she added.
"We could go back and track down all the people who failed with the therapies against Alzheimer's disease," Nelson said. "But what we really need to do is move on and try to get these people out of Alzheimer's clinical trials – and instead put them into their own clinical trials."
Silverberg describes the new article as a "road map" for research that could change as we discover more about the disease. And researchers can not do that without a large and diverse group of patients, she added.
"It will probably take years and research participants to help us understand all of this," she said.