AGING
May 3, 2019

Not Alzheimer's

There are many forms of dementia, including a newly-identified variety. This may not matter to caregivers, but it could make a difference to treatment.

People often use the terms Alzheimer's and dementia interchangeably. But not all dementia is caused by Alzheimer's disease. “More than 200 different viruses can cause the common cold,” said Peter Nelson of the Sanders-Brown Center on Aging at the University of Kentucky. “So why would we think there is just one cause of dementia?”

This might not make a difference to someone who cares for or lives with a dementia sufferer. Symptoms are similar and people with other types of dementia can be just as hard to care for as people with Alzheimer's. But it could make a great deal of difference in dementia research and may affect the kind of treatment best suited to an individual.

LATE is most common in the oldest of the old and is almost as prevalent among them as Alzheimer's, but if you examine the brain, the two diseases look very different.

Alzheimer's disease (AD) is definitively diagnosed after death, when a brain autopsy can be done to determine whether beta-amyloid deposits — the sticky substance that clogs up neurons and is a hallmark of Alzheimer's disease — are present. Many of the people who enrolled in clinical trials for Alzheimer's drugs probably did not have these deposits, so how can you properly test an anti-amyloid treatment on people who don't have amyloid deposits?

It has been known for years that a large number of people who die at an advanced age have symptoms of dementia with no sign of amyloid deposits or deposits of another common Alzheimer's hallmark, tau protein, in their brains at autopsy.

There are now strong indications that a different protein, TDP-43, is involved in many of these cases, and this type of dementia has been named Limbic-predominant age-related TDP-43 encephalopathy or LATE. LATE is most common in the oldest of the old and is almost as prevalent among them as Alzheimer's, but if you examine the brain, the two diseases look very different.

Recently, a group of international researchers, co-chaired by Nelson, set out to establish diagnostic criteria and other guidelines for LATE and to chart a course for future research. The team found that like Alzheimer's disease, LATE affects multiple areas of cognition, eventually impairing the activities of daily life, but it seems to progress more slowly than Alzheimer's does. The two often occur together, and the combination appears to cause a more rapid decline in people than either would alone.

It's time to stop thinking of dementia as a one-size-fits-all disease, Nelson believes. “LATE probably responds to different treatments than AD, which might help explain why so many past Alzheimer's drugs have failed in clinical trials,” he said. “Now that the scientific community is on the same page about LATE, further research into the ‘how’ and ‘why’ can help us develop disease-specific drugs that target the right patients.”

An article on the group's findings appears in the journal, Brain.

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