HAI Book 2025 - Flipbook - Page 119
Corriveau-Lecavalier, Nick
9
Characterization of a limbic-predominant amnestic neurodegenerative
syndrome
Nick Corriveau-Lecavalier1,2, Anne Waniger1, Nikki Stricker1, Mary Machulda1, Julie Fields1,
Hugo Botha2, Jonathan Graff-Radford2, Vijay Ramanan2, Stuart McCarter2, Aivi Nguyen3, R.
Ross Reichard3, Bradley Boeve2, David Knopman2, Val Lowe4, Dennis Dickson5, Melissa
Murray5, Neill Graff-Radford6, Ronald Petersen2, Clifford Jack4, David Jones2
1
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, US
Department of Neurology, Mayo Clinic, Rochester, MN, US
3
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, US
4
Department of Radiology, Mayo Clinic, Rochester, MN, US
5
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, US
6
Department of Neurology, Mayo Clinic, Jacksonville, FL, US
2
We recently proposed criteria for a limbic-predominant amnestic neurodegenerative syndrome (LANS). LANS
presents at old age with a mild, memory-dominant course, and localizes to the limbic system. A detailed
characterization of LANS is needed to guide clinical care and research efforts. Additionally, it remains unclear
whether individuals with LANS and positive Alzheimer9s disease (AD) biomarkers experience worse outcomes. We
compared longitudinal neuropsychological and multimodal imaging (FDG-PET, tau-PET) data between individuals
with LANS (n = 56; amyloid-positive n = 33, amyloid-negative n = 17) and cases of autopsy-proven AD
neuropathologic change (ADNC) without limbic-predominant age-related TDP-43 encephalopathy (LATE) that had
an antemortem history of Alzheimer9s-type dementia (referred to as AD; n = 42). Measures of immediate recall
were less impaired in LANS compared to AD, while delayed recall was equally impaired in both. Dichotomizing
LANS according to amyloid status revealed a steeper decline in story memory in amyloid-positive LANS than AD.
Executive functions and visuospatial processing were less impaired in LANS compared to AD, regardless of
amyloid status (Fig.1). LANS individuals were selectively impaired on a measure of salient semantic knowledge,
which included questions about World War II and 9/11/2001 (administered at baseline only). FDG-PET revealed
greater medial temporal lobe hypometabolism and less neocortical hypometabolism in LANS compared to AD,
irrespective of amyloid status (Fig.2). Tau-PET findings showed higher regional uptake in AD compared to LANS,
regardless of amyloid status, although tau-PET positivity was heterogeneously distributed within amyloidpositive LANS (Fig.3). LANS is characterized by memory deficits and loss of knowledge about salient events, with
these impairments associated with limbic degeneration. Amyloid status was associated with a steeper decline of
story memory in LANS compared to AD, although non-memory domains remained relatively spared, regardless of
amyloid status. This emphasizes the role of a functional anatomic classification to predict outcomes in
degenerative syndromes.
HAI2025 - 119
