Summary: Researchers have established new criteria for limbic-predominant amnestic neurodegenerative syndrome (ANS), a memory loss disorder often confused with Alzheimer’s disease.
Unlike Alzheimer’s disease, LANS syndrome progresses more slowly and has a better prognosis. The criteria help doctors diagnose LANS syndrome in living patients using brain scans and biomarkers. This advancement contributes to better management and personalized treatments for memory loss.
Highlights:
- Distinct syndrome: LANS is often confused with Alzheimer’s disease but progresses more slowly.
- Diagnostic criteria: New criteria allow diagnosis using brain scans and biomarkers.
- Improved prognosis: Patients with LANS have a better prognosis than those with Alzheimer’s disease.
Source: Mayo Clinic
Mayo Clinic researchers have established new criteria for a memory loss syndrome in older adults that specifically affects the brain’s limbic system. This syndrome can often be confused with Alzheimer’s disease.
The good news: Limbic-predominant amnestic neurodegenerative syndrome, or ANS, progresses more slowly and has a better prognosis, and is now more clearly defined for doctors working to find answers for patients suffering from memory loss.
Before researchers developed clinical criteria published in the journal Brain communicationsThe characteristics of the syndrome could only be confirmed by examining brain tissue after a person’s death.
The proposed criteria provide a framework for neurologists and other experts to classify the disease in patients with symptoms, providing a more accurate diagnosis and potential treatments. They take into account factors such as age, severity of memory impairment, brain scans and biomarkers indicating deposits of specific proteins in the brain.
The criteria were developed and validated using data from more than 200 participants in the Mayo Clinic Alzheimer’s Disease Research Center, Mayo Clinic Study of Aging, and Alzheimer’s Disease Neuroimaging Initiative databases.
Understanding the disease will lead to better management of symptoms and more tailored therapies for patients with this type of cognitive decline, which is distinct from Alzheimer’s disease, said Dr. David T. Jones, a neurologist at the Mayo Clinic and lead author of the study.
“In our clinical work, we see patients whose memory symptoms appear to mimic those of Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s disease. Until now, there hasn’t been a specific medical diagnosis to base this on, but now we can offer them answers,” Jones says.
“This research creates a clear framework that other health care professionals can use to care for their patients. It has major implications for treatment decisions, including amyloid-lowering drugs and new clinical trials, as well as for counseling on prognosis, genetics and other factors.”
According to Nick Corriveau-Lecavalier, Ph.D., first author of the study, decades of work are underway to understand and classify the different types of dementia. These findings build on scientists’ ongoing efforts to untangle neurological disorders that often have similar symptoms or can occur simultaneously, but whose treatments and prognoses can be radically different.
“Historically, you could see an 80-year-old with memory problems and think that they might have Alzheimer’s disease, and that’s often how we think today,” explains Corriveau-Lecavalier.
“With this paper, we describe a different syndrome that occurs much later in life. Often, the symptoms are limited to memory and do not progress to other cognitive domains, so the prognosis is better than in Alzheimer’s disease.”
With no signs of Alzheimer’s disease, the researchers looked at a possible culprit: a buildup of a protein called TDP-43 in the limbic system that scientists found in autopsied brain tissue from older people.
The researchers classified the accumulation of these protein deposits as TDP-43 age-related limbic-predominant encephalopathy, or LATE. These protein deposits may be associated with the newly defined memory loss syndrome, but there are other likely causes as well and more research is needed, the authors say.
With the clinical criteria established by Jones, Corriveau-Lecavalier and their co-authors, practitioners could soon diagnose LANS in patients so that those living with memory loss can better understand treatment options and potential disease progression, paving the way for research to shed more light on the characteristics of the disease.
Funding: The research was supported 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 Dr. Corinne Schuler Foundation.
Drs. Jones and Corriveau-Lecavalier reported no conflicts of interest. A full list of co-authors and financial information is available in the manuscript.
About this news on research on local networks, memory and aging
Author: Emily DeBoom
Source: Mayo Clinic
Contact: Emily DeBoom – Mayo Clinic
Picture: Image credited to Neuroscience News
Original research: Free access.
“Clinical criteria for a predominantly limbic amnestic neurodegenerative syndrome” by David T. Jones et al. Brain communications
Abstract
Clinical criteria for amnestic neurodegenerative syndrome with limbic predominance
Predominant limbic degeneration has been associated with various underlying etiologies and with advanced age, predominant episodic memory impairment, and slow clinical progression. However, the neurological syndrome associated with predominant limbic degeneration is not defined.
This effort is essential to distinguish such a syndrome from those arising from neocortical degeneration, which may differ in terms of underlying etiology, disease course, and therapeutic needs.
We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome that is strongly associated with limbic-predominant age-related TDP-43 encephalopathy but also with other pathological entities.
The criteria incorporate baseline, standard, and advanced features, including advanced age at assessment, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degeneration, and low probability 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 pathological outcomes.
We reviewed autopsied patients from the Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with antemortem amnestic-predominant syndrome (Mayo, not = 165; Alzheimer’s Disease Neuroimaging Initiative, not = 53) and who presented with neuropathological alteration of Alzheimer’s disease, age-related TDP-43 encephalopathy with limbic predominance or both pathologies at autopsy.
These neuropathology-defined groups represented 35, 37, and 4% of cases in the Mayo cohort, and 30, 22, and 9% of cases in the Alzheimer’s Disease Neuroimaging Initiative cohort, respectively.
The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest probability, patients with limbic-predominant age-related TDP-43 encephalopathy having the highest probability, and patients with both conditions having intermediate probabilities.
Logistic regression using the criteria 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 probability had a milder and slower clinical course and more severe temporomandibular degeneration compared with those with low probability.
Classification of patients with both Alzheimer’s disease-related neuropathologic changes and age-related limbic-predominant TDP-43 encephalopathy from the Mayo cohort according to their probabilities revealed that those with higher probabilities had greater temporo-limbic degeneration and a slower rate of decline and those with lower probabilities had greater lateral temporo-parietal degeneration and a faster rate of decline.
The implementation of criteria for a limbic-predominant amnestic neurodegenerative syndrome has implications for disambiguating the different etiologies of progressive amnestic presentations in older adults and guiding diagnosis, prognosis, treatment, and clinical trials.