Researchers have developed clinical criteria for diagnosing limbic-predominant amnestic neurodegenerative syndrome (LANS) using patient data from the Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative to improve the accuracy of diagnosing and differentiating the condition from other neurologic disorders.
LANS, characterized by predominant limbic degeneration in older adults, is associated with age-related TDP-43 encephalopathy (LATE), marked by gradual episodic memory impairment and a slow clinical progression. The proposed criteria, published in Brain Communications, include core, standard, and advanced features, such as older age at evaluation, mild clinical syndrome, hippocampal atrophy, semantic memory impairment, limbic hypometabolism, and absence of neocortical degeneration. These criteria aimed to distinguish LANS from amnestic syndromes resulting from neocortical degeneration, which typically exhibit faster progression and nonmemory features.
To validate these criteria, the researchers analyzed data from 218 autopsied patients with amnestic syndromes, including 165 from the Mayo Clinic and 53 from the Alzheimer’s Disease Neuroimaging Initiative cohorts, comparing their clinical and pathological outcomes. In the Mayo Clinic cohort, 35% of cases had Alzheimer's disease neuropathological changes (ADNC), 37% had LATE, and 4% had both pathologies. In the Alzheimer’s Disease Neuroimaging Initiative cohort, 30% of cases had ADNC, 22% had LATE, and 9% had both pathologies.
The logistic regression model that utilized LANS criteria features to predict TDP-43 showed a balanced accuracy of 74.6% in the Mayo Clinic cohort. When tested on an external cohort, the model demonstrated a balanced accuracy of 73.3%. They found that LANS criteria effectively categorized cases into likelihoods of having LATE or Alzheimer’s disease. Patients with higher LANS likelihoods exhibited slower clinical decline and more severe temporo-limbic degeneration, while those with lower likelihoods had faster decline and more lateral temporo-parietal degeneration.
The study indicated that these newly developed LANS criteria could potentially guide the diagnosis, prognosis, and treatment of amnestic syndromes in older adults.
Full disclosures can be found in the published study.