HAI Book 2025 - Flipbook - Page 381
Silva-Rodríguez, Jesús
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Heterogeneity of FDG-PET patterns among tau-negative amnestic
patients
Jesús Silva-Rodríguez1, Alexis Moscoso2, Miguel A. Labrador-Espinosa2, Pascual SánchezJuan1, Michael Scholl2, Michel J. Grothe1
1
Reina Sofia Alzheimer Centre, CIEN Foundation, ISCIII, Madrid, ES
Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry,
University of Gothenburg, Gothenburg, SE
2
Introduction: Approximately 20-30% of patients diagnosed with Alzheimer9s disease (AD) dementia do not meet
pathological criteria for AD, with an even higher proportion in amnestic mild cognitive impairment (aMCI). Among
tau-negative (Tau-) patients, limbic-predominant age-related TDP-43 encephalopathy (LATE) emerges as a key
diagnostic alternative, particularly in older individuals. LATE is associated with a characteristic temporo-limbic
hypometabolic pattern on FDG-PET imaging. However, the heterogeneity of hypometabolic patterns among Tauamnestic patients remains poorly understood.
Methods: 360 patients (261 aMCI, 99 AD dementia) from the Alzheimer9s Disease Neuroimaging Initiative (ADNI)
underwent both 18F-Flortaucipir and 18F-FDG-PET scans. Participants were classified as Tau+ or Tau- based on a
visual assessment. Tau- patients were further screened for hypometabolism. LATE-like patterns were identified
through automated pattern-matching to autopsy-confirmed cases. Additional FDG-PET patterns were explored
using hierarchical clustering. Differences in age, hippocampal volume, and cognitive measures were analyzed
between groups.
Results: 185 patients (162 aMCI) were classified as Tau-. Among these, 37 patients (39%) showed a LATE-like
pattern (see Fig.1). Hierarchical clustering of the remaining patients identified three distinct clusters: a leftlateralized temporal pole pattern suggestive of semantic dementia (C1, 18%), a posterior-occipital pattern typical
for dementia with Lewy bodies (C2, 24%), and a diffuse frontal pattern of unknown origin (C3, 19%). LATE-like
patients were significantly older (p=0.02) and had greater memory impairment (p=0.02) and hippocampal atrophy
(p=0.03) compared to other Tau- individuals. When applying the newly proposed clinical criteria for probable
LATE, i.e. Tau- amnestic profile at elevated age (>75y) and significant hippocampal atrophy, most patients (59%)
showed a LATE-like pattern, although other patterns remained present (C1=19%, C2=9%, C3=13%).
Conclusions: FDG-PET provides valuable diagnostic insights after a negative Tau-PET scan. In older Tauamnestic patients with hippocampal atrophy, LATE-like temporo-limbic hypometabolism is most common, but
distinct hypometabolic patterns suggestive of other neurodegenerative conditions are also present.
HAI2025 - 381
