Limbic-predominant age-related TDP-43 encephalopathy (LATE)

Key points

Recently defined, LATE is a physical brain disorder that can contribute to cognitive decline and behaviour changes.
LATE tends to show in people over the age of 80. Although old age is a risk factor, dementia in general is not part of normal aging.
LATE cannot yet be diagnosed with certainty until after death, by autopsy.
At least five genes signal a risk for LATE and other forms of dementia.
On its own, LATE has a slower rate of clinical change than Alzheimer's disease.
In combination with Alzheimer’s disease or other brain disorders there may be a more rapid rate of decline.
Researchers are currently looking for ways to more confidently distinguish LATE from Alzheimer’s disease.

About limbic-predominant age-related TDP-43 encephalopathy

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined cause of dementia. Similar to other forms of dementia, such as Alzheimer’s disease, it causes problems with memory and thinking but has different underlying causes.

Dementia is the result of changes in the brain that cause nerve cells (neurons) to stop working properly. For example, brain changes associated with Alzheimer’s disease are caused by the buildup of amyloid plaques and tau proteins.

On its own, LATE has a slower rate of clinical change than Alzheimer's disease. More than 3,000 donors examined with LATE, also showed evidence of Alzheimer’s disease. This suggests that having more than one of these brain disorders may contribute to more rapid decline than either disease alone.

Causes of LATE

TDP-43 protein helps to regulate gene expression in the brain and other tissues.

Autopsy studies of donor brains showed certain patterns of misfolded TDP-43 where memory and cognitive function occurs. Researchers defined this pattern of misfolded protein deposit as LATE.

Results of more than 6,000 donor autopsy studies, with an average age at death of 88 years, found that 40 per cent had LATE type TDP-43 protein deposits. 25 per cent of these donors also experienced deficits in memory and thinking.

Signs and symptoms of LATE

The symptoms of LATE are similar to those of Alzheimer’s. These include:

problems with memory
difficulty thinking and making decisions
trouble finding the right words
wandering or getting lost.

Diagnosing LATE

Currently, LATE cannot be diagnosed in living people. It can only be diagnosed after death, by autopsy.

If you are concerned about memory problems or other symptoms of dementia, talk with a doctor. You may be referred to a neurologist (a doctor specialising in disorders of the brain and nervous system).

A specialist in dementia can look at your clinical history and your risk factors for LATE. They may suggest an MRI or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. If these scans show brain shrinkage (atrophy), as well as reduced neuron activity, in the part of the brain where memory formation occurs the diagnosis of LATE is supported.

Hold the Moment Podcast: Where to from here?
Hear how people living with dementia handled their diagnosis experience, and how they found a positive way forward, in this first episode of the Hold the Moment Podcast.
Listen
https://www.dementia.org.au/living-dementia/hold-moment-podcast/episode-where-here

Treatment and management of LATE

Right now, there’s no cure for Limbic-Predominant Age-Related TDP-43 Encephalopathy.

However, there are lifestyle changes to improve brain health, and support services to ensure your best quality of life as you live with the condition.

If you are concerned about your memory or behaviour, talk to your doctor. They may suggest a mental status examination to find out how severe the cognitive impairment is.

Your doctor may also prescribe medicines for other conditions like restlessness or depression, or to help you sleep better.

Staying physically active and socially connected, and managing stress, can also be beneficial in helping you live well for as long as possible. Talk to your doctor about the best options for you.

Talking to a counsellor or psychologist can help you manage the changes in your behaviour and mood.

Occupational therapy can help you to function well at home.

What’s next for LATE research?

Researchers are currently investigating how to distinguish LATE from Alzheimer’s disease to better diagnose it before death, and potential treatments (these may target the TDP-43 protein).