Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic

Article Article scientifique Article Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic eng 2025-12-22 2026-01-27 author Roveta Fausto 0000-0001-7230-7819 Aging Brain and Memory Clinic, Department of Neuroscience "Rita Levi-Montalcini", University of Turin, Italy.,Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland.,Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Switzerland. 428883 dept de réadaptation et gériatrie (MIGRG) author Pizzini Francesca B 0000-0002-6285-0989 Department of Engineering for Innovation Medicine, University of Verona, Italy. author Natale Valerio Radiology, Department of Diagnostic and Public Health, University of Verona, Italy. author Scheffler Max 0000-0003-2274-5129 Division of Radiology, Geneva University Hospitals, Switzerland. 686304 Département de radiologie et informatique médicale (RADIO) author Garibotto Valentina 0000-0003-2422-698X Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Switzerland.,Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Switzerland.,CIBM Center for Biomedical Imaging, Geneva, Switzerland; and. 704817 Département de radiologie et informatique médicale (RADIO) author Martins Mendes Augusto José 0000-0002-9497-0707 Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland.,Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Switzerland. 405544 dept de réadaptation et gériatrie (MIGRG) author Wang Chen Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland. author Lathuilière Aurélien 0000-0002-5191-5214 Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland.,Laboratory for translational research in neurodegeneration, University of Geneva, Switzerland. 557604 dept de réadaptation et gériatrie (MIGRG) Aurélien Lathuiliere author Chicherio Christian Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland. 85466 author Rainero Innocenzo Aging Brain and Memory Clinic, Department of Neuroscience "Rita Levi-Montalcini", University of Turin, Italy. author Frisoni Giovanni 0000-0001-7075-7082 Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland.,Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Switzerland. 810190 dept de réadaptation et gériatrie (MIGRG) author Ribaldi Federica 0000-0001-9208-4472 Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland.,Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Switzerland. 920118 dept de réadaptation et gériatrie (MIGRG) e214477 10.1212/wnl.0000000000214477 41428981 0028-3878 PMC12746730 Background and objectives: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative condition often overlapping clinically with Alzheimer disease (AD). No established in vivo biomarkers exist for LATE. The amygdalar atrophy scale (AAS) is a visual MRI rating tool scoring the amygdala as AAS0 (no atrophy), AAS1 (mild-to-moderate atrophy), or AAS2 (severe atrophy) and is associated with TDP-43 neuropathology in limbic regions. This study describes the clinical, neuroimaging, and longitudinal cognitive profiles of individuals classified using a proposed framework that combines the AAS with established AD biomarkers. Methods: This retrospective study included individuals attending the Geneva Memory Center (2014-2022) who underwent T1-weighted MRI, as well as clinical and neuropsychological assessments. Participants were categorized with an etiologic grouping defined as No-AD/No-LATE (AAS0 , negative AD biomarkers), AD (AAS0 , positive AD biomarkers), LATE (AAS1-2 , negative AD biomarkers), or AD/LATE (AAS1-2 , positive AD biomarkers). Group differences were compared using Kruskal-Wallis or χ2 tests. Differences in MRI brain volumes and cortical thickness between groups were examined with analysis of covariance. Cognitive trajectories using Mini-Mental State Examination (MMSE) scores over 30 months were estimated with linear mixed-effects models accounting for baseline age and education. Results: The analytic sample included 469 participants (mean age 71.2 ± 8.5 years, 53% female). The No-AD/No-LATE group exhibited the highest MMSE scores (N = 181, 27.9 ± 2.2), outperforming AD (N = 146, 24.2 ± 4.9), LATE (N = 36, 26.2 ± 3.2), and AD/LATE (N = 106, 22.5 ± 5.3) groups (p < 0.001). On the Free and Cued Selective Reminding Test, the No-AD/No-LATE group showed the highest scores (15.1 ± 1.8); the LATE and AD groups performed similarly (13.3 ± 3.5 and 12.5 ± 4.0), both exceeding the AD/LATE group (10.6 ± 4.1) (p < 0.001). LATE and AD/LATE groups showed lower volumes/thicknesses in TDP-43-related regions compared with AD and No-AD/No-LATE groups. Longitudinally, the LATE group maintained cognitive stability as the No-AD/No-LATE group (β = -0.010, 95% CI -0.096 to 0.075, p = 0.813), whereas both AD (β = -0.136, 95% CI -0.184 to -0.088, p < 0.001) and AD/LATE (β = -0.139, 95% CI -0.196 to -0.082, p < 0.001) groups showed faster decline over time. Discussion: Patients identified as LATE by the integration of AAS with AD biomarkers had generally mild amnestic cognitive impairment, significant limbic atrophy, and slow decline over time, all features consistent with previous autopsy series. Moreover, AD/LATE cases were more impaired than those with LATE or AD alone. Prospective and neuropathologic validation is warranted. Aged Aged, 80 and over Alzheimer Disease / diagnostic imaging Alzheimer Disease / pathology Amygdala / diagnostic imaging Amygdala / pathology Atrophy / pathology Dementia Female Humans Magnetic Resonance Imaging Male Middle Aged Neuropsychological Tests Retrospective Studies TDP-43 Proteinopathies / diagnostic imaging TDP-43 Proteinopathies / pathology TDP-43 Proteinopathies / psychology Dewey 616.8 Dewey 616.0757 Dewey 618.97 16 Centre interfacultaire de neurosciences 0D9 62 Département de radiologie et informatique médicale 227 65 Département de réadaptation et gériatrie 22B false 926 Imagerie per-opératoire multi-modalité en radiologie interventionnelle 949 1222 Laboratoire de neuroimagerie et de traceurs moléculaires innovants 984 1451 Recherche translationnelle en neurodégénérescence 1068 853 Troubles de mémoire et maladie d'Alzeimer 935 Neurology 106 2 6068d7f1-6313-4feb-b177-70b7d565de47 Article (Published version) Public roveta-et-al-2025-utility-of-the-am.pdf 889239 application/pdf CC BY-4.0 5e3d82b0f2866214b7544cba1d50d93e43d73c7929d7c0134d8ab0757192ac74 b035989d-45ce-4bd3-a5fb-f004d0e84cee Supplemental data Public supplements.pdf 429194 application/pdf 85b5566209c657d1e43ba85c5ba248201711bd4b31034c356130722281c035f7 openAccess Centres et instituts / Centre interfacultaire de neurosciences Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale Faculté de médecine / Section de médecine clinique / Département de réadaptation et gériatrie

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic	Neurology			2026	12	41

Archive ouverte UNIGE

Roveta, Fausto