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Late Disease - Causes, Symptoms, Diagnosis and Treatment

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The LATE (limbic-predominant age-related TDP-43 encephalopathy) disease is a mental disorder characterized by dementia; for more information, read below.

Medically reviewed by

Dr. S. Adithya

Published At November 23, 2022
Reviewed AtJanuary 19, 2024

What Is Dementia?

Dementia is a disorder characterized by symptoms that affect thinking, memory, and the ability to interact with the people around them. Dementia can be the clinical symptom of various disorders; it mainly involves the impairment of two or more brain functions. Dementia remains a silent symptom for years before it is clinically presented.

What Are the Types of Dementia?

  • Alzheimer's disease: It is considered to be the most common cause of dementia.

  • Vascular Dementia: A type of dementia that results from damage to the blood vessels that carry blood to the brain.

  • Lewy body dementia.

  • Frontotemporal dementia.

  • Mixed dementia.

  • LATE disease.

What Is LATE Disease?

The LATE disease is a disorder characterized by dementia and presents symptoms similar to Alzheimer's. It is a kind of dementia that impairs social, cognitive, and memory abilities. The term LATE stands for limbic-predominant age-related TDP-43 encephalopathy. TDP-43 is a protein that plays an important role in the progression of the disease as this protein accumulates in the brain cells and destroys them by injuring these cells.

Some of the common parts of the brain that are affected by LATE include:

  • The Amygdala: An area that regulates emotions.

  • The Hippocampus: Center for learning and memory.

  • The Temporal Lobe: Involved in understanding and processing words.

  • The Frontal Lobes: A region where information is stored and manipulated.

Knowing more about the LATE disease is important as it affects the large population in the older generation. It was diagnosed when many people with dementia died, and not found similar features to Alzheimer's like telltale signs in brain autopsy findings when examined. The disease is also called TDP-43 proteinopathy.

Who Is at Risk of Developing Late?

LATE typically affects older people, especially those who are above 80. While getting older is a risk factor for LATE, dementia is not a normal aspect of growing older.

The chance of having LATE can also be raised by genetics. The risk of LATE is linked to at least five genes. Other types of dementia may potentially be more common due to these same genes.

What Are the Stages of the LATE Disease?

The LATE disease is categorized into three stages according to the progress of the disease, which is as follows:

  • Stage 1: Involves only the amygdala.

  • Stage 2: Involves the amygdala and hippocampus.

  • Stage 3: Involves areas of stages one and two along with the middle frontal gyrus.

What Are the Causes of LATE Disease?

The exact cause of the disorder remains unknown, and studies have suggested that LATE disorder and Alzheimer's are not the same. In the brain and other organs, the TDP-43 (transactive response DNA-binding protein) protein often aids in controlling the expression of certain genes. Accumulation of this protein has been linked to cognitive impairment through the degeneration of memory-related brain regions, including the hippocampus.

Recent autopsies using donated brain tissue have revealed that older persons may have a particular arrangement of misfolded TDP-43 proteins. This arrangement of misfolded deposits of proteins was named LATE by researchers. Other uncommon forms of dementia, like frontotemporal lobar degeneration, are also considered to play some role in developing the LATE disease.

What Are the Symptoms of the LATE Disease?

The clinical presentation of the late disease is similar to that of Alzheimer's; the disorder is characterized by amnestic cognitive syndrome, which includes impaired cognitive functions like:

  • Memory loss.

  • Difficulty in understanding and remembering words.

  • Impaired working memory as these people have shrunk hippocampi responsible for learning and memorizing.

  • Speech is limited to a few or one word.

  • Loss of appetite.

  • Disturbed bowel movements.

People who have LATE may:

  • Wander or become disoriented

  • Make incorrect decisions

  • Lose things or struggle with driving

  • Find it challenging to maintain personal hygiene

Eventually, doing everyday tasks like getting dressed, making meals, or paying payments becomes difficult for someone with LATE. Compared to other types of dementia, LATE causes a slower rate of mental loss. This results in a gradual progression of symptoms as opposed to a sudden one.

How Is the LATE Disease Diagnosed?

The LATE disease is difficult to diagnose; the worst part is that the disease cannot be diagnosed when the person is still alive. However, the patient's clinical presentation is memory loss and difficulty finding words and carrying out normal daily activities. The diagnosis is confirmed by carrying out an autopsy. An autopsy is performed as a part of the neuropathological evaluation. An autopsy is the only way a person can determine the exact cause of dementia.

However, in the case of symptomatic individuals, a LATE diagnosis might be proposed by:

  • Medical history

  • Results obtained from MRI or fluorodeoxyglucose (FDG)-positron emission tomography (PET)

  • Eliminating alternative causes

A doctor might check for brain abnormalities that could be brought on by LATE. Symptoms of brain atrophy, or shrinkage, including atrophy of the brain's memory-forming regions may be among them. Both autopsy and MRI examinations reveal these alterations. Compared to atrophy, thinning appears to be a more reliable measure of the disease's severity.

Arterial wall thickening and hardening (arteriolosclerosis), which is frequent among LATE patients, is another indicator that may point to a diagnosis. To determine the extent of the cognitive impairment, a medical professional may recommend a mental status evaluation if they think someone may have a LATE illness.

How Is the LATE Disease Treated?

LATE is often not diagnosed during its early stages; therefore, treating LATE is difficult. In most cases, the disease is confused with Alzheimer's disease. Researchers have even proved that the drugs used in treating Alzheimer's, like Donepezil, Rivastigmine, Memantine, and Galantamine, can be used effectively in treating patients with LATE disorder.

The World Health Organization (WHO) has established guidelines that can assist manage dementia symptoms and enhance general health. These guidelines include:

  • Increasing exercise.

  • Keeping up a nutritious diet.

  • Reducing alcohol consumption.

  • Giving up smoking.

  • Treating long-term illnesses such as diabetes, high blood pressure, depression, obesity, and high cholesterol.


LATE is a type of dementia that is caused due to TDP-43 encephalopathy; the disease is diagnosed and occurs in the late stages of life, hence the name. The individual presents with symptoms caused due to mental impairment, including memory loss and social impairment, and can progress to a level where a person finds difficulty in carrying out daily activities on their own; forgetfulness is also observed in such individuals.

Treating such conditions becomes difficult as they are not diagnosed without an autopsy; therefore, the disease cannot be confirmed when the person is alive. Cases with the LATE disorder are commonly confused with Alzheimer's. Thus, these patients are treated with the medications used to treat Alzheimer's. The disease, its etiology, and its treatment are not well understood as it is still being researched and studied. However, the literature so far suggests that the cause of dementia is not only Alzheimer's disease but can even be other possible disorders like the LATE disease.

Frequently Asked Questions


How to Differentiate Alzheimer’s and Late?

Alzheimer’s and LATE are diseases of dementia that have similar symptoms but have different causes. Proteins that are involved in each disease vary. TDP-43 is involved with LATE, and amyloid beta and neurofibrillary tangles are involved with Alzheimer’s disease. 


What Is the Full Form of Late in Medical Terms?

LATE stands for limbic-predominant age-related TDP-43 encephalopathy in medicine. TDP-43 is a protein that is responsible for the progression of the disease. This protein accumulates in the brain cells and injures them resulting in the destruction of the cells.


Mention About Late Alzheimer’s Disease.

Late Alzheimer’s disease develops after 65 years of age. It is caused by a number of variants, especially occurring in the APOE gene. Symptoms of both early and late Alzheimer’s disease are the same. These diseases are caused by the build-up of toxic protein fragments. These protein fragments are amyloid beta and neurofibrillary tangles. Individuals lose the ability to respond to the outer environment, to do conversations, and also to control movements.  


Name the Stages of Late.

Based on the progression, the late disease is divided into three stages.
Stage 1: It involves only the amygdala.
Stage 2: It involves the amygdala and hippocampus.
Stage 3: It involves the areas of stage 1 and stage 2 with the middle frontal gyrus.


Why the Term Late Is Mentioned by Doctors?

Individuals who are affected by LATE are of the above 85-year age group. Hence, doctors call it LATE. The diagnosis cannot be made when an individual is living. Autopsy of the brain is made after the death of an individual to diagnose or differentiate it from Alzheimer’s disease. This also may be the reason for it to be called LATE.


Which Stage of Alzheimer’s Is Considered Death?

Stage 7 is called Alzheimer’s death, as this stage is described as a terminal illness, and individuals in this stage are nearing death. In this stage, individuals lose the ability to respond to the outer environment. 


Mention About the Late Brain.

The LATE-affected brain looks different from the brain affected with Alzheimer’s disease. The key feature that affects the brain is the dysfunction of the TDP-43 protein. This protein is responsible for gene expression in the brain. MISfolded TDP-43 may be seen in individuals who are more than 85 years of age. The LATE affected brain looks different from Alzheimer’s Brain.


When to Consider an Individual to Be Affected by Late?

An individual presents symptoms that are similar to Alzheimer’s disease. Generally occurs in 80 years of age or more than 80 years of age group. May account for 17 percent of all dementia cases. Even in this disease, memory loss, thinking, and reasoning may be affected. This disease can be diagnosed only after an autopsy of the brain. This cannot be done when an individual is alive. Shrinkage in the hippocampus may be seen. 


Mention the Causes of Late Dementia.

The exact cause of the disease is not known. Dysfunction and misfolding of TDP-43 protein in the brain are found to be responsible for the disease to occur. Frontotemporal lobar degeneration is another form of dementia that may play a role in causing LATE disease.


Whether Alzheimer’s Is Considered a Slow Death?

Yes. The way people die of Alzheimer’s disease differs from one individual to another. There is a basic pattern that is followed in this process. They slowly lose the ability to control basic body functions like eating, drinking, and toileting. After some time, slowly, their body may shut down, and they may not be able to move.


Whether the Brain Age Considered to Be a Real Thing?

No, brain age is an index to quantify brain health as it deviates from the normal brain age trajectory. Higher than expected brain age is thought partially to reflect the above-average rate of brain aging.


What Can Be Done to Increase Memory?

Memory power can be increased by doing the following activities. They are:
- Doing physical activities- increases the blood flow to the brain as well as other body parts.
- Staying mentally active.
- Spending time with loved ones.
- Keeping oneself active.
- Have a good sleep.
- Eating a healthy diet.
- Management of chronic illnesses.


How to Assess if a Brain Is Healthy?

Brain health can be assessed by knowing about an individual’s lifestyle, which includes healthy eating, drinking plenty of water, sleeping well, socializing with others, and managing stress well.


What Are the Habits Responsible for Damage of the Brain?

Habits that damage the brain are:
- Not having enough sleep.
- Smoking habit.
- Being alone for a longer time.
- Being too stationary.
- Overeating.
- Eating more junk food.
- Listening to headphones for longer periods of time.
- Spending more time in the dark.


How to Assess the Mental Age?

It is calculated by subtracting the birth year from the current year. Mental age, also known as intellectual age, is determined by attitude, behavior, and intelligence. The mental age test was first introduced by Alfred Binet in 1905.
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Dr. S. Adithya
Dr. S. Adithya



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