Late, A New Kind Of Dementia

Alzheimer’s disease is today one of the most widespread in the world with more than 46 million people affected. Thus, the study of dementias in general is one of the greatest challenges facing science today. Despite having come a long way, there is still much to discover and it is, therefore, inevitable to continue to find new finds. An example, the appearance of a new type of dementia, LATE.

Although several types of dementia are known and the possibility that they coexist with each other, there are certain inconsistencies that have drawn the attention of scientists. For example, that in patients with severe Alzheimer’s and older than 80 years, the cognitive decline exceeded the expected. Apparently, this new type of dementia could explain these gaps.


The acronym LATE refers to predominantly Limbic Age-related TDP-43 encephalopathy. LATE is related to the TDP-43 protein, which has already been discovered and related to other degenerative diseases, such as amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD).

TDP-43 is a protein that binds to RNA and DNA and performs multiple functions of regulating gene expression.

The new proposed dementia, LATE, occurs in older age, especially those over 80 years of age. Thus, working groups for the diagnosis of Alzheimer’s have proposed this term with the intention of including other general TDP-43 proteinopathies that are associated with cognitive impairment, including, for example, hippocampal sclerosis and its subtypes.

TDP-43 proteinopathy  has been associated with a progressive amnesic syndrome that has been mimicked with Alzheimer’s disease. This, coupled with the lack of knowledge and the lack of tests to diagnose proteinopathy in vivo, has led some scientists to assure that a high percentage of people diagnosed with Alzheimer’s could actually have LATE.

TDP-43 proteinopathy involves the loss of its normal immunoreactivity, with the transfer to the cell cytoplasm, as well as the abnormal accumulation of the protein.

How to observe it

Currently, TDP-43 alterations can only be observed by performing a post-mortem  brain autopsy. Based on these types of studies and their findings, experts have proposed a three-phase evolution of the disease:

  • Proteinopathy in the tonsil.  It has been observed that the volume and shape of the amygdala is affected in LATE, and that these structural changes are indicative of cognitive decline. In fact, the relationship between these observations in the amygdala and the change due to LATE is much stronger than between hippocampal atrophy and Alzheimer’s.
  • Proteinopathy in the hippocampus. Hippocampal atrophy has been found to be greater in patients who have had LATE than in those with pure Alzheimer’s. This atrophy of the hippocampus is asymmetric and appears to follow a front-to-back path.
  • Proteinopathy in the medial frontal gyrus. This area is located in the frontal lobe, so dementia would already affect higher cognitive processes of attention or learning.

Neuropsychological characteristics

Like other dementias, LATE dementia is accompanied by an amnesic syndrome that can evolve and affect other cognitive domains that affect activities of daily living. However, there are certain aspects that present a somewhat different pattern.

The scant evidence so far indicates that patients with pure LATE show a more gradual decline compared to those with Alzheimer’s. And, as expected, those with LATE comorbidity and Alzheimer’s have a more severe and rapid decline.

Those with LATE have a more marked deterioration in episodic memory, but also show severe impairment of other functions, especially in later stages. For example, it appears that patients with good verbal fluency despite poor ability to remember a list of words are at higher risk of developing LATE.

Future directions

It is still too early to establish neuropsychological profiles and we do not even have neuroimaging instruments to observe the alteration of proteins in vivo. Thus, we can only wait for future research that will provide new biomarkers and indicators, as well as motor, autonomic or neuropsychiatric characteristics.