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Newly Discovered Illness May Cause Nearly 1 in 5 Dementias, Experts Say

HealthDay News
by By Amy Norton
HealthDay Reporter
Updated: Apr 30th 2019

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TUESDAY, April 30, 2019 (HealthDay News) -- Elderly adults commonly have memory and thinking problems that look a lot like Alzheimer's disease, but they might really be suffering from a different form of dementia.

That's according to an international panel of experts who are giving the disease a name for the first time, and detailing what's known about it so far.

Writing in the April 30 issue of the journal Brain, they dub the condition limbic-predominant age-related TDP-43 encephalopathy -- with the more memorable acronym, LATE.

LATE mainly affects people older than 80, the experts explained. And it may account for about 17% of all cases of dementia.

That fairly high prevalence helps explain a puzzling phenomenon, according to Dr. Peter Nelson, a professor at the University of Kentucky, who co-authored the report.

Some people who die with what appears to be Alzheimer's do not show telltale signs of the disease when their brains are autopsied -- namely, abnormal protein clumps known as plaques and tangles. That means their dementia symptoms did not arise from Alzheimer's.

"This is part of a growing understanding that not all dementias are the same," Nelson said.

As for symptoms, LATE does "mimic" Alzheimer's, said Nina Silverberg, director of the Alzheimer's Disease Centers Program at the U.S. National Institute on Aging. It causes memory loss and problems with thinking and reasoning that ultimately keep elderly people from being able to care for themselves.

But the LATE-affected brain looks very different from the Alzheimer's brain.

A key feature, according to Silverberg, is dysfunction in a protein called TDP-43, which helps control gene expression in the brain.

Researchers have long known that problems in TDP-43 are bad news: "Mis-folded" TDP-43 proteins are a culprit in most cases of amyotrophic lateral sclerosis (ALS, or "Lou Gehrig's disease") and an uncommon form of dementia called frontotemporal lobar degeneration.

But many elderly people have a certain amount of mis-folded TDP-43 in their brains. According to the report, one-quarter of adults older than 85 have enough of those abnormal proteins to hinder their memory and thinking.

People with LATE also frequently show a severe shrinkage in the brain's hippocampus, a structure involved in memory and learning.

But those findings are only scratching the surface of the disease. "There's a lot we don't know at this point," Silverberg said.

There is no way to diagnose LATE while a person is still living. Only a brain autopsy can help pinpoint it as the cause of dementia.

And it's not clear, Silverberg said, when the disease process gets going: Is LATE like Alzheimer's, beginning years or even decades before clear symptoms arise?

According to Nelson, one of the most important goals now is to find "biomarkers" for LATE. Biomarkers are measurable signs of a disease process -- like protein levels in the blood or structural abnormalities seen on brain scans.

There are biomarkers for Alzheimer's, Nelson pointed out. Researchers can use PET scans of the brain, or samples of spinal fluid, to detect amyloid and tau -- the proteins that form plaques and tangles in the brain.

If researchers can find markers of LATE, they can better understand the disease -- and possibly develop drugs for it.

In the real world, Alzheimer's is usually diagnosed not through PET scans, but through assessments of symptoms.

That means there are people diagnosed with "probable" Alzheimer's who, in fact, have LATE, according to Keith Fargo, director of scientific programs and outreach for the Alzheimer's Association.

"But at this point," he said, "that's probably OK."

That's because current medications for dementia target symptoms -- not underlying disease processes like amyloid build-up, Fargo explained.

But many trials are investigating drugs that do aim at the underlying process. "In the future," Fargo said, "medications will be more specific, and it will be important to distinguish Alzheimer's from LATE."

In the past, Fargo noted, Alzheimer's trials might have been hindered by the mistaken inclusion of people with LATE. But, he added, that shouldn't be as much of an issue now, since researchers do have ways to objectively look for Alzheimer's.

It's also possible that certain broad measures for brain health -- like blood pressure control, a healthy diet, exercise and mental stimulation -- could help slow down dementia, regardless of the cause. Fargo said the Alzheimer's Association is sponsoring a trial, called U.S. Pointer, that is studying that question.

More information

The Alzheimer's Association has an overview of the different forms of dementia.