In Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION : Hippocampal sclerosis of aging (HS) is defined by end-stage histological findings, strongly associated with limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE). We aimed to characterize features of early HS to refine the understanding of its role within combined pathology.
METHODS : We studied 159 brain donations from the multimodal Vallecas Alzheimer's Center Study. A staging system (0 to IV) was developed to account for HS progression and analyzed in relation to pre-mortem cognitive and magnetic resonance imaging (MRI) data.
RESULTS : Our HS staging system displayed a significant correlation with disease duration, cognitive performance, and combined neuropathologies, especially with LATE. Two-level assessment along the hippocampal longitudinal axis revealed an anterior-posterior gradient of HS severity. In vivo MRI showed focally reduced hippocampal gray matter density as a function of HS staging.
DISCUSSION : The association of this staging system with clinical progression and structural differences supports its utility in the characterization and potential in vivo monitoring of HS.
HIGHLIGHTS : The definition of hippocampal sclerosis of aging (HS) is currently limited to an end-stage pathological fingerprint. We characterize early HS histological features to define a complete staging system. The proposed staging displays a parallel but not identical progression to limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE). The proposed staging also reflects the expected demographic and cognitive differences associated with HS. In vivo magnetic resonance imaging (MRI) showed focal hippocampal gray matter loss as a function of HS staging.
Ortega-Cruz Diana, Uceda-Heras Alicia, Iglesias Juan Eugenio, Zea-Sevilla María Ascensión, Strange Bryan, Rabano Alberto
2023-Jan-24
dementia, hippocampal sclerosis of aging, hippocampus, limbic age-related TDP-43 encephalopathy, magnetic resonance imaging, neuropathology
