LANS Dementia Gets New Diagnostic Criteria to Distinguish It From Alzheimer's Disease

A previously overlooked type of dementia, which can readily be confused with Alzheimer's disease, has been given a new name and dedicated diagnostic criteria.

Researchers have named the condition limbic-predominant amnestic neurodegenerative syndrome (LANS). They hope their work will help healthcare professionals support and advise people experiencing different types of memory loss.

LANS dementia and its diagnostic criteria

LANS involves brain alterations that differ from those seen in Alzheimer's. It usually develops more slowly, produces less severe symptoms and mainly affects people aged over 80.

As with Alzheimer's, a conclusive diagnosis can only be made after death through an autopsy.

Neurologist Nick Corriveau-Lecavalier and colleagues from the Mayo Clinic, alongside researchers from other institutions in the US and Spain, have set out a formal framework to help distinguish LANS from Alzheimer's in people living with memory problems.

"In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer's disease, but when you look at their brain imaging or biomarkers, it's clear they don't have Alzheimer's," says senior author and Mayo neurologist David Jones.

"Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers."

This more detailed diagnosis takes account of factors including age, the extent of memory loss, brain imaging and biomarkers.

In a trial, the new criteria correctly classified dozens of people who had died with either Alzheimer's disease or LANS using only health information collected during their lives. Although the approach was not flawless, it achieved accuracy of more than 70 percent.

The link between LANS and LATE

The clinical criteria for LANS appear highly likely to be associated with brain changes produced by limbic-predominant age-related TDP-43 encephalopathy, also known as LATE.

In the study, most people with LATE-related brain changes received the highest LANS diagnostic scores. However, the researchers stress that, although the terms are "highly associated", LANS can technically describe any type of dementia that causes degeneration in the limbic system.

LATE-related brain changes are very common in older people, appearing in around 40 percent of brains examined at autopsy after age 85. They involve a build-up of a protein called TP-43 within the limbic system, a brain network that helps regulate memory, emotions and behaviour.

These changes differ clearly from the tau protein tangles found in Alzheimer's disease, which generally accumulate in brain regions responsible for spatial awareness and spatial reasoning.

An international consensus report published in 2019 recommended including LATE-related brain changes within the dementia classification system.

How LANS differs from Alzheimer's disease

Alzheimer's and LANS share many symptoms, so they are frequently mistaken for one another. LANS can also sometimes occur alongside Alzheimer's, making diagnosis still more difficult.

Nevertheless, they are separate diseases.

After reviewing available research on both dementia types, Mayo Clinic researchers identified several important differences in the way LANS and Alzheimer's appear clinically.

People with LANS generally first develop episodic memory loss. This impairs their ability to remember contextual information or the names of people and objects, while also reducing verbal fluency. Their visuospatial processing, however, remains comparatively better preserved than it does in people with Alzheimer's.

MRI research also indicates that hippocampal volume loss is more strongly linked to LANS than to Alzheimer's, in which volume loss tends to be concentrated in the neocortex.

LANS seemingly begins more gradually and has milder effects than Alzheimer's disease, which declines more quickly. The decline is steeper still in people with both LANS and Alzheimer's.

"One example that can be a potential source of clinical conundrums is the limbic variant Alzheimer's disease, where tau predominantly localizes to the limbic system and therefore qualifies for LANS," the authors explain.

"The advanced LANS criteria in combination with visual assessment of tau-PET can help in determining which pathology has the highest likelihood of driving clinical symptoms."

Separating the different forms and mechanisms of dementia is evidently challenging, but the Mayo team intends to keep refining its LANS classification.

The study was published in Brain Communications.