Better L.A.T.E. Than Never? A New Type of Dementia is Described...

(This blog originally appeared in LinkedIN as an article, 5/16/19)

A new type of dementia is in town.  It’s called LATE.  It has many similarities with Alzheimer’s Disease, in fact it overlaps with Alzheimer’s in many cases.  Last month an international consortium of dementia researchers published a summary of what we know about LATE thus far.  They also agreed on the name, they proposed standard protocols to use going forward so that research and drug development could happen faster, and they alerted the public and medical community that this new category of dementia is real and needs our attention.

LATE is an acronym that stands for:

•      Limbic-predominant

•      Age-related

•      TDP-43

•      Encephalopathy

While the name is a tongue-twister, it does point to several of the ways in which LATE is either similar or distinct from Alzheimer’s Disease.  

Both diseases affect the hippocampus, but in LATE the damage is a bit more spread out within the limbic system, that part of the brain that controls memory, personality, and behavior.  Thus limbic-predominant.

Although both Alzheimer’s and LATE are age-related, their age at onset is distinct.  The earliest signs of Alzheimer’s tend to appear in the early to mid 70’s. Early symptoms of LATE appear in the mid 80’s instead, so nearly a decade later.

The hallmark plaques of Alzheimer’s Disease are mainly composed of amyloid-beta.  There are plaque-like deposits in the brain tissue of LATE patients as well, but the main protein is called TDP-43.  I find the distinction encouraging because so far, all the clinical trials that targeted amyloid-beta have failed.  We desperately need new targets for drug-development and now we have one.  It’s also possible that one of the reasons those clinical trials failed is because there were LATE patients mixed into the study population, so scientists are trying to figure out how important that may or may not have been.

And lastly, both are slow, progressive diseases that affect memory and one’s ability to care for oneself, so in that sense they are both encephalopathies.

Most of what is known about LATE comes from studies of people who died and donated their bodies to science.  The findings that pathologists discovered under the microscope were then correlated back with the patient’s symptoms and the natural history of their dementia before they died.  From this work it seems that Alzheimer’s and LATE can overlap.  When one happens without the other, both of the diseases appear to progress slowly, but when they occur together the symptoms are more severe and the dementia progresses faster. 

I can think of many patients who had what looked like Alzheimer’s but their diseases progressed at very different rates. Some developed symptoms and then passed away within 5-7 years.  Others were (or are) still alive over 10-15 years later.  Is it possible that some had the 2 dementia’s combined while others only had one or the other?  Unfortunately, there’s no way to tease these two dementias’ apart in the clinic: no lab or screening tests exist to do that just yet. 

Clearly, we are still in the early innings when it comes to LATE.  The work done by the LATE consortium is a significant step forward and will jumpstart several new avenues of research.  Given the vast impact that dementia is having across our society, that is welcome news to this geriatrician’s ears.