New criteria defined for memory loss condition often mistaken for Alzheimer's

• Other types of dementia and cognitive conditions are many times misdiagnosed as Alzheimer’s disease.
• Researchers have identified another memory-loss condition called Limbic-predominant Amnestic Neurodegenerative Syndrome (LANS) that is frequently misdiagnosed as Alzheimer’s.
• Scientists have developed new criteria to help doctors better diagnose the condition.

Although Alzheimer’s disease is the most common type of dementia , other types such as Lewy body dementia and frontotemporal dementia can mistakenly be diagnosed as Alzheimer’s because they all share very similar symptoms.

This is also the case for other age-related neurological conditions such as mild cognitive impairment .

Now, scientists from the Mayo Clinic have identified another memory-loss condition found in older adults that is frequently misdiagnosed as Alzheimer’s disease. Researchers have developed new criteria to help doctors in diagnosing this condition called Limbic-predominant Amnestic Neurodegenerative Syndrome (LANS).

The study was recently published in the journal Brain Communications .

What is LANS?

According to David T. Jones, MD , a neurologist at the Mayo Clinic and senior author of this study, LANS is a progressive degenerative condition of the body’s limbic system — a brain system important for memory — with a variety of underlying causes.

“When this system degenerates, it becomes difficult for people to form new memories, often leading to difficulty recalling recent events, repeating statements that have already been said, and problems recalling names,” Jones told Medical News Today .

Traditionally, Jones said, it has been hard for doctors to diagnose a person with LANS because memory problems like the ones seen in LANS are not very specific.

“Many non-degenerative conditions can cause memory problems and degenerative diseases that involve non-limbic brain regions also produce memory symptoms,” he continued. “Using brain imaging and other biomarkers is required to be confident that a patient’s symptoms are coming from an isolated degeneration of the limbic system.”

“Advances in biomarkers for Alzheimer’s disease, a condition that often impacts the neocortex , have allowed for more clearly differentiating LANS from the majority (of) symptoms caused by Alzheimer’s disease,” he added. “Although some forms of Alzheimer’s disease can cause LANS, this is not the most common cause.”

Developing diagnosing criteria for LANS

Jones and his team developed new criteria to help physicians in diagnosing LANS that include the following core clinical factors:

• presents with a slow, predominant neurodegenerative condition with memory loss that has gradually progressed for two or more years that cannot be linked to another disease
• age of 75 years or older
• mild clinical syndrome
• disproportionate hippocampal atrophy
• impaired semantic memory
• limbic hypometabolism and absence of neocortical degeneration
• low likelihood of neocortical tau pathology

This new criteria was developed and validated using data from over 200 participants in databases for the Mayo Clinic Alzheimer’s Disease Research Center, the Mayo Clinic Study of Aging, and the Alzheimer’s Disease Neuroimaging Initiative.

“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,” Jones says in a press release .

“Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers. This research creates a precise framework that other medical professionals can use to care for their patients. It has major implications for treatment decisions, including amyloid-lowering drugs and new clinical trials, and counseling on their prognosis, genetics, and other factors.”
— David T. Jones, MD, senior author

Examining the protein TDP-43

Researchers also looked at a specific protein called TDP-43 when creating this new criteria. Previous studies have found build-ups of TDP-43 in the limbic system of autopsied brain tissue of older adults, which is referred to as limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) .

“The TDP-43 protein is key to defining LATE-NC,” Jones said. “This is something that pathologists observe at autopsy and indicate that a certain type of degenerative condition of the limbic system was affecting a patient during their life.”

“You can diagnose LANS in the mild cognitive impairment stage or the dementia stage. Mild cognitive impairment and dementia are generic terms for cognitive symptoms with a variety of underlying causes. LANS can also have a variety of underlying causes, but they are more limited to degenerative conditions isolated to the limbic system, with LATE-NC being the most common but rare forms of Alzheimer’s disease or other tauopathies can also cause LANS,” he continued.

LANS clinical trials needed

Jones said that these new criteria can be used in clinical practice now to inform the diagnosis of LANS, which can then guide medical counseling and management recommendations.

“As research on LANS advances, medical counseling and management recommendations will improve,” he said. “I use (this criteria) in my practice now. All clinical trials for Alzheimer’s disease would be improved if they include LANS likelihoods and evaluate responses to various therapeutics based on this. We also need tailored clinical trials for subjects diagnosed with LANS. We also need studies of the clinical utility of the LANS diagnosis that included longitudinal observational cohorts with a variety of measures common to age and dementia research.”

“Understanding age-related memory changes is crucial for early detection and intervention on underlying causes, improving quality of life, and developing tailored therapies,” Jones added. “It also empowers patients and families with knowledge, supporting better care and mental health outcomes while informing public health policies for aging populations.”

Good news for adults with isolated memory loss

MNT also spoke with David Merrill, MD, PhD, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in Santa Monica, CA, about this research.

Merrill said that this is good news for older adults presenting with isolated memory loss.

“They may have this newly identified disorder, LANS, which is expected to remain a mild clinical syndrome over time,” he explained.

“Alzheimer’s disease and other memory syndromes have a more rapid, severe, and debilitating progressive course than what is described in LANS. Receiving a diagnosis of LANS may mean that the feared worst-case scenario will not come to pass. Namely, these LANS patients do not actually have Alzheimer’s.”
— David Merrill, MD, PhD

“Forming a cross-institutional registry of these cases so we can identify what underlying causes are associated with developing LANS will help identify what treatments will need to be delivered and/or developed to help these patients,” Merrill added.