summary: Researchers have established new criteria for limbic-predominant amnesic neurodegenerative syndrome (LANS), a memory-loss disorder often mistaken for Alzheimer’s disease.
Unlike Alzheimer’s disease, LANS progresses slowly and has a good prognosis. This criteria will help doctors diagnose LANS in living patients using brain scans and biomarkers. This advancement will help better manage memory loss and individualize treatment.
Key Facts:
- Characteristic syndromes: LANS is often mistaken for Alzheimer’s disease, but it progresses more slowly.
- Diagnostic Criteria: The new criteria allow for diagnosis using brain scans and biomarkers.
- Improved prognosis: The prognosis for people with LANS is better than for those with Alzheimer’s disease.
sauce: Mayo Clinic
Mayo Clinic researchers have established new criteria for a memory loss syndrome in older adults that specifically affects the limbic system of the brain and is often mistaken for Alzheimer’s disease.
The good news is that limbic predominant amnesic neurodegenerative syndrome (LANS) progresses slowly, has a good prognosis, and is becoming better defined for doctors trying to find answers for their memory-loss patients.
Researchers develop clinical criteria before they are published in journals. Brain communicationHowever, the characteristics of this syndrome could only be confirmed by examining brain tissue after a person’s death.
The proposed criteria would provide a framework for neurologists and other specialists to classify the condition in symptomatic patients, providing more accurate diagnoses and potential treatments. They would take into account factors such as age, severity of memory impairment, brain scans and biomarkers that show deposits of certain proteins in the brain.
The criteria were developed and validated using data from more than 200 participants from the Mayo Clinic Alzheimer’s Disease Research Center, the Mayo Clinic Study of Aging, and the Alzheimer’s Disease Neuroimaging Initiative databases.
Understanding this pathology may lead to better symptom management and more customized treatments for patients suffering from this type of cognitive decline that is different from Alzheimer’s disease, said David T. Jones, M.D., a neurologist at Mayo Clinic and senior author of the study.
“In our clinical practice, we see patients whose symptoms of memory loss appear to be similar to Alzheimer’s, but when we look at brain images and biomarkers, it’s clear that it’s not Alzheimer’s. Before, we weren’t able to point to a specific medical diagnosis, but now we can give them some answers,” Jones says.
“This study creates a precise framework that other medical professionals can use to treat patients. It will have a major impact on treatment decisions, including amyloid-lowering medications, new clinical trials, and counseling regarding prognosis, genetics and other factors.”
“Research to understand and classify the different types of dementia has been ongoing for decades,” said lead author Nick Corriveau-Lecavalier, PhD. These findings build on scientists’ ongoing efforts to understand neurological disorders that often have similar symptoms or occur together, but have vastly different treatments and prognoses.
“Historically, if someone in their 80s had memory problems, you might think they might have Alzheimer’s, and that’s still often the case today,” Corriveau-Lecavalier says.
“This paper describes a different syndrome that occurs much later in life, with a better prognosis than Alzheimer’s disease because symptoms are often limited to memory and do not progress to affect other cognitive domains.”
In the absence of signs of Alzheimer’s, the researchers focused on the possibility that one cause could be the buildup of a protein called TDP-43 in the limbic system, which scientists had found in autopsy brain tissue from older people.
The researchers classify the accumulation of these protein deposits as limbic-predominant age-related TDP-43 encephalopathy (LATE).The protein deposits may be associated with a newly defined memory loss syndrome, but other causes are also possible and require further study, the authors say.
The clinical criteria established by Jones, Corriveau-Lecavalier and their co-authors will soon enable doctors to diagnose LANS in their patients, allowing people suffering from memory loss to better understand treatment options and possible disease progression, and opening the door to research that will further characterize the disease.
Funding: This 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 Dekelbaum 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 report no conflicts of interest. A full list of co-authors and financial disclosures can be found in the manuscript.
About this LANS, Memory and Aging Research News
author: Emily DeBoom
sauce: Mayo Clinic
contact: Emily DeBoom – Mayo Clinic
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Clinical criteria for limbic-dominant amnesic neurodegenerative syndromes” by David T. Jones et al. Brain communication
Abstract
Clinical criteria for limbic-dominant amnesic neurodegenerative syndromes
Predominant limbic degeneration has been associated with a variety of underlying etiologies, advanced age, predominant impairment of episodic memory, and slow clinical progression, but no neurological syndrome associated with predominant limbic degeneration has been defined.
This effort is important to distinguish such syndromes from those resulting from neocortical degeneration, which may have different underlying etiologies, disease courses, and treatment needs.
We propose clinical criteria for a limbic-predominant amnesic neurodegenerative syndrome that is highly associated not only with limbic-predominant age-related TDP-43 encephalopathy but also with other pathologies.
The criteria incorporate core, standard, and advanced features, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, semantic memory impairment, limbic hypometabolism, absence of neocortical degeneration, and low likelihood of neocortical tau, along with degrees of certainty (highest, high, medium, low).
We operationalized this set of criteria using clinical, imaging, and biomarker data and examined its association with clinical and pathologic outcomes.
We screened autopsy patients from the Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohort and identified antemortem dominant amnesia syndrome (Mayo, yeah = 165; Alzheimer’s Disease Neuroimaging Initiative, yeah = 53) and had Alzheimer’s disease neuropathological changes, limbic-predominant age-related TDP-43 encephalopathy, or both at autopsy.
These neuropathologically defined groups accounted for 35, 37, and 4% of cases, respectively, in the Mayo cohort and 30, 22, and 9% of cases, respectively, in the Alzheimer’s Disease Neuroimaging Initiative cohort.
This criterion effectively classified the cases, with the least likely to have Alzheimer’s disease, the most likely to have limbic-predominant age-related TDP-43 encephalopathy, and an intermediate probability for patients with both pathologies.
Logistic regression using baseline characteristics as predictors of TDP-43 achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample prediction in the external cohort achieved a balanced accuracy of 73.3%. Patients with high probability had a milder, slower clinical course and more severe temporolimbic degeneration compared with patients with low probability.
When patients from the Mayo cohort were classified according to the likelihood of having both Alzheimer’s disease neuropathological changes and limbic-predominant age-related TDP-43 encephalopathy, it was found that patients with a high likelihood had more temporolimbic degeneration and a slower rate of decline, whereas patients with a low likelihood had more temporoparietal degeneration and a faster rate of decline.
Implementing the criteria for limbic-predominant amnesic neurodegenerative syndromes will have implications for clarifying the various etiologies of progressive amnesia in later life and for guiding diagnosis, prognosis, treatment, and clinical trials.
