Summary: Researchers established new criteria for Limbic-predominant Amnestic Neurodegenerative Syndrome (LANS), a memory-loss condition often mistaken for Alzheimers disease.

Unlike Alzheimers, LANS progresses more slowly and has a better prognosis. The criteria help doctors diagnose LANS in living patients using brain scans and biomarkers. This advancement aids in better management and tailored treatments for memory loss.

Key Facts:

Source: Mayo Clinic

Researchers atMayo Clinichave established new criteria for a memory-loss syndrome in older adults that specifically impacts the brains limbic system. It can often be mistaken for Alzheimers disease.

The good news: Limbic-predominant Amnestic Neurodegenerative Syndrome, or LANS, progresses more slowly and has a better prognosis, and is now more clearly defined for doctors working to find answers for memory loss patients.

Prior to the researchers developing clinical criteria published in the journalBrain Communications, the hallmarks of the syndrome could be confirmed only by examining brain tissue after a persons death.

The proposed criteria provide a framework for neurologists and other experts to classify the condition in patients living with symptoms, offering a more precise diagnosis and potential treatments. They consider factors such as age, severity of memory impairment, brain scans, and biomarkers indicating the deposits of specific proteins in the brain.

The criteria were developed and validated using data from more than 200 participants in databases for theMayo Clinic Alzheimers Disease Research Center, theMayo Clinic Study of Agingand the Alzheimers Disease Neuroimaging Initiative.

Understanding the condition will lead to better management of symptoms and more tailored therapies for patients suffering from this type of cognitive decline, distinct from Alzheimers disease, saysDavid T. Jones, M.D., a Mayo Clinic neurologist and senior author of the study.

In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimers disease, but when you look at their brain imaging or biomarkers, its clear they dont have Alzheimers. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers, Jones says.

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.

Decades of work to understand and classify different types of dementia is ongoing, says Nick Corriveau-Lecavalier, Ph.D., the papers first author. These findings build upon scientists continued efforts to untangle neurological conditions that often have similar symptoms or can occur simultaneously, but can have drastically different treatments and prognoses.

Historically, you might see someone in their 80s with memory problems and think they may have Alzheimers disease, and that is often how its being thought of today, Corriveau-Lecavalier says.

With this paper, we are describing a different syndrome that happens much later in life. Often, the symptoms are restricted to memory and will not progress to impact other cognitive domains, so the prognosis is better than with Alzheimers disease.

Without signs of Alzheimers disease, the researchers looked at the involvement of one possible culprit a buildup of a protein called TDP-43 in the limbic system that scientists have found in the autopsied brain tissue of older adults.

Researchers have classified the build-up of these protein deposits aslimbic-predominant age-related TDP-43 encephalopathy, or LATE. These protein deposits could be associated with the newly defined memory loss syndrome, but there are also other likely causes and more research is needed, the authors say.

With clinical criteria established by Jones, Corriveau-Lecavalier and co-authors, practitioners could soon diagnose LANS in patients so those living with memory loss might better understand options for treatment and potential progression of the disease, opening doors for research to further illuminate the characteristics of the disease.

Funding: The research was funded in part by National Institutes of Health grants P30 AG062677, P50 AG016574, U01 AG006786, R37 AG011378 and R01 AG041851 and by the Robert Wood Johnson Foundation, the Elsie and Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation and the Foundation Dr. Corinne Schuler.

Drs. Jones and Corriveau-Lecavalier reported no conflicts of interest. A complete list of co-authors and financial disclosures is available in the manuscript.

Author: Emily DeBoom Source: Mayo Clinic Contact: Emily DeBoom Mayo Clinic Image: The image is credited to Neuroscience News

Original Research: Open access. Clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome by David T. Jones et al. Brain Communications

Abstract

Clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome

Predominant limbic degeneration has been associated with various underlying aetiologies and an older age, predominant impairment of episodic memory and slow clinical progression. However, the neurological syndrome associated with predominant limbic degeneration is not defined.

This endeavour is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying aetiology, disease course and therapeutic needs.

We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome that is highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.

The criteria incorporate core, standard and advanced features, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degeneration and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate and low).

We operationalized this set of criteria using clinical, imaging and biomarker data to validate its associations with clinical and pathologic outcomes.

We screened autopsied patients from Mayo Clinic and Alzheimers Disease Neuroimaging Initiative cohorts and applied the criteria to those with an antemortem predominant amnestic syndrome (Mayo,n= 165; Alzheimers Disease Neuroimaging Initiative,n= 53) and who had Alzheimers disease neuropathological change, limbic-predominant age-related TDP-43 encephalopathy or both pathologies at autopsy.

These neuropathology-defined groups accounted for 35, 37 and 4% of cases in the Mayo cohort, respectively, and 30, 22 and 9% of cases in the Alzheimers Disease Neuroimaging Initiative cohort, respectively.

The criteria effectively categorized these cases, with Alzheimers disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods and patients with both pathologies having intermediate likelihoods.

A logistic regression using the criteria features as predictors of TDP-43 achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample predictions in an external cohort achieved a balanced accuracy of 73.3%. Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods. S

tratifying patients with both Alzheimers disease neuropathological change and limbic-predominant age-related TDP-43 encephalopathy from the Mayo cohort according to their likelihoods revealed that those with higher likelihoods had more temporo-limbic degeneration and a slower rate of decline and those with lower likelihoods had more lateral temporo-parietal degeneration and a faster rate of decline.

The implementation of criteria for a limbic-predominant amnestic neurodegenerative syndrome has implications to disambiguate the different aetiologies of progressive amnestic presentations in older age and guide diagnosis, prognosis, treatment and clinical trials.

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New Type of Age-Related Memory Loss Identified - Neuroscience News