Clinical and molecular correlates of limbic age-related TDP-43 encephalopathy (LATE) 18F-FDG-PET pattern in amnestic mild cognitive impairment

This study aimed to test the ability to visually detect the characteristic medial temporal and limbic hypometabolic pattern of limbic age-related TDP-43 encephalopathy (LATE) in 18F-FDG-PET of patients with amnestic mild cognitive impairment (aMCI) and evaluate its prognostic value. We included 70 patients with aMCI who underwent 18F-FDG-PET, amyloid-PET, tau-PET, and structural MRI, as well as baseline and follow-up cognitive evaluation. 18F-FDG-PET scans were analyzed visually with single-subject maps, categorized as normal, Alzheimer's disease (AD)-like, LATE-like, or other neurodegenerative diseases, while blinded from other data. Clinical and biomarker features as well as cognitive trajectories were compared between groups. 25 scans were classified as normal, 25 as AD-like, 12 as LATE-like, and 8 as others. Patients with AD-like patterns were younger, had lower MMSE scores, inferior-to-medial temporal metabolism ratio, and greater hippocampal atrophy and cortical tau load than subjects with normal scans. Patients with LATE-like patterns had lower MMSE scores and more hippocampal atrophy than subjects with normal scans. Patients with LATE-like patterns were significantly older, had greater inferior-to-medial temporal metabolism ratio, greater amygdalar atrophy, and lower cortical tau load than subjects with AD-like patterns. Only subjects classified as AD-like showed a faster cognitive decline than negative scans. LATE-like hypometabolic pattern in aMCI can identify a subgroup of subjects distinct from AD and controls in terms of clinical severity, medial temporal atrophy, cortical tau load, and cognitive decline, supporting the utility of 18F-FDG-PET as a biomarker that provides inferential support for the specific detection of LATE.