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

Purpose 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 F-18-FDG-PET of patients with amnestic mild cognitive impairment (aMCI) and evaluate its prognostic value. Methods We included 70 patients with aMCI who underwent F-18-FDG-PET, amyloid-PET, tau-PET, and structural MRI, as well as baseline and follow-up cognitive evaluation. F-18-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. Results 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. Conclusion 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 F-18-FDG-PET as a biomarker that provides inferential support for the specific detection of LATE.