L.A.T.E. Dementia is a brain disorder that mimics clinical features of Alzheimer’s disease. This name is an acronym for the following type of dementia:
Limbic-predominant Age-related TDP-43 Encephalopathy, or L.A.T.E.
New guidelines will help doctors identify patients with this common memory-loss syndrome that is often misdiagnosed as Alzheimer’s. The diagnostic criteria for limbic-predominant age-related TDP-43 encephalopathy (LATE) are published this month in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association. The guidelines are from an international team led by Penn Medicine researchers. These guidelines are an important first step in advancing clinical trials and treatments for this lesser-known, but common type of memory loss disorder.
L.A.T.E. differs from Alzheimer’s in that:
- L.A.T.E. can progress slower
- It can cause less impairment of cognitive functions
- It’s most common in individuals generally over 80 years of age.
- Alzheimer’s is characterized by buildup of proteins called beta-amyloid and tau on the brain. L.A.T.E. is caused by a buildup of a different protein, called TDP-43.
- Patients with L.A.T.E. have a more stable course and live longer.
- L.A.T.E. predominantly affects memory, while individuals with Alzheimer’s experience impairment of more wide-ranging roles of cognition, like executive functioning, planning, language and visuospatial function.
- Alzheimer’s can be detected in living patients by testing for beta-amyloid and tau. There are no physical tests for L.A.T.E.’s TDP-43, so doctors need to use more subjective cognitive evaluations and tests that rule out the alternatives.
“Clear guidelines to diagnose different diseases not only help inform patients and their families of their prognosis but also help to guide decisions about which treatments to pursue,” said David Wolk, MD, co-director of the Penn Memory Center and first author of the research. “As therapies that clear the amyloid associated with Alzheimer’s disease become available to patients, we need to be able to determine whether a patient actually has these proteins in their brain and will benefit from the treatment. And if they don’t, we need to identify what disease they do have, which can be LATE.” (Continued below video…)
When is Alzheimer’s disease not Alzheimer’s disease in older adults?
LATE is a newly characterized type of dementia that causes memory loss in individuals generally over 80 years of age. Because the main symptom of LATE is memory loss, it is often incorrectly diagnosed as AD. However, LATE has a different underlying cause than AD; while AD is characterized by buildup of proteins called beta-amyloid and tau on the brain, LATE is caused by a buildup of a different protein, called TDP-43, which was discovered at Penn Medicine by Breakthrough Prize-winning researchers Virginia Lee and colleagues.
A prevalent, but not widely known condition
Autopsy analysis has revealed that LATE is quite common among adults over 80 years old; TDP-43 buildup associated with LATE was present in 40 percent of adults in that age group. Autopsy of individuals with AD revealed that 55 percent also had LATE. As compared to people with only AD, those with only LATE have different cognitive symptoms. LATE predominantly affects memory, while individuals with AD experience impairment of more wide-ranging roles of cognition, like executive functioning, planning, language and visuospatial function. Individuals with LATE tend to also have a slower progression of symptoms than AD, but when individuals have both LATE and AD, symptoms tend to progress faster. Research suggests that patients with just LATE have a more stable course and live longer than patients with just AD, or patients with both LATE and AD.
Limbic-predominant Age-related TDP-43 Encephalopathy, or LATE, as seen by microscope and MRI. Nelson et. al. and Brain, DOI: 10.1093/brain/awz099.
Diagnosing L.A.T.E. Takes Special Dementia Expertise
Unlike beta-amyloid and tau, there is no test for TDP-43, and its presence on the brain can only be confirmed by brain autopsy after death. In the new report, researchers detail criteria for diagnosing LATE by itself or when it co-occurs with AD, using cognitive evaluations, MRI scans looking for atrophy in the hippocampus, and testing for the presence of beta-amyloid and tau in cerebrospinal fluid and in PET scans of the brain.
These diagnostic criteria also help differentiate LATE from other types of dementia, like frontotemporal lobar degeneration (FTLD), which also involves TDP-43 buildup, or dementia with Lewy bodies, where proteins mis-fold and accumulate on the brain. In FTLD, individuals experience loss of executive function and language rather than memory loss, which can be noted by cognitive evaluation. Additionally, these individuals will not exhibit atrophy of the hippocampus or medial temporal lobe. In dementia with Lewy bodies, individuals experience impaired motor function, in addition to other cognitive impairments.
“Being able to accurately diagnose LATE in both forms sets the stage to engage in further, important research,” Wolk said. “Not only can we use this diagnosis to develop clinical trials for TDP-43 drugs, but we can also investigate the efficacy of existing therapies on individuals with both LATE and AD, and potentially develop and test new therapies that target both diseases. These criteria offer a first step in this direction.”
What is TDP-43 and Hippocampal Sclerosis?
TDP-43 (transactive response DNA binding protein of 43 kDa) is a protein that normally helps to regulate gene expression in the brain and other tissues. Prior studies found that unusually misfolded TDP-43 has a causative role in most cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. However, these are relatively uncommon diseases. A significant new development seen in recent research is that misfolded TDP-43 protein is very common in older adults.
TDP-43 pathology is also commonly associated with hippocampal sclerosis, the severe shrinkage of the hippocampal region of the brain — the part of the brain that deals with learning and memory. Hippocampal sclerosis and its clinical symptoms of cognitive impairment can be very similar to the effects of Alzheimer’s.
“Recent research and clinical trials in Alzheimer’s disease have taught us two things: First, not all of the people we thought had Alzheimer’s have it; second, it is very important to understand the other contributors to dementia,” said Nina Silverberg, Ph.D., director of the Alzheimer’s Disease Centers Program at NIA. In the past many people who enrolled in clinical trials likely were not positive for amyloid. “Noting the trend in research implicating TDP-43 as a possible Alzheimer’s mimic, a group of experts convened a workshop to provide a starting point for further research that will advance our understanding of another contributor to late life brain changes,” Silverberg explained. In addition to U.S. scientists, experts included researchers from Australia, Austria, Sweden, Japan, and the United Kingdom with expertise in clinical diagnosis, neuropathology, genetics, neuropsychology and brain imaging.
I recently was diagnosed with indications that “oncoming” (my term) Alzheimer’s. I have a doctor’s appointment tomorrow and I will ask him about how he knows what I have THANKS for this timely info!