Overview on epidemiology and neuropathologic staging of limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic changes (LATE‐NC)

Abstract

AbstractBackgroundLimbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is increasingly appreciated to have a very large impact on public health. The goal of this presentation is to provide an overview about what is known about the epidemiology of LATE, and also to describe some recent changes to the criteria for the diagnostic classification of LATE neuropathologic change (LATE‐NC). The prevalence of LATE‐NC and Alzheimer’s disease neuropathologic changes (ADNC) are each challenging to assess definitively, due to the requirement of state‐of‐the‐art autopsy verification across human populations.MethodA set of neuropathologic and clinical data were compiled from 13 high quality community‐ and population‐based longitudinal studies. The total number of participants included was 6,196, and the average age of death was 88.1 years. This study provided a credible estimate of the current prevalence of LATE‐NC in advanced age, with or without comorbid ADNC. Diagnostic classification also must take into account neuropathologic heterogeneity.ResultLATE‐NC was seen in almost 40% of participants and in ∼25% of those lacking ADNC. A total of 3,267 of these participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP‐43 inclusions (FTLD‐TDP). Another focus of the talk is recent research findings that have enabled increasingly precise guidance on how to differentiate LATE‐NC from other subtypes of TDP‐43 pathology (e.g., FTLD‐TDP and amyotrophic lateral sclerosis [ALS]), and how to render diagnoses in unusual situations in which TDP‐43 pathology does not match the staging scheme proposed in 2019. Specific recommendations are made about when to avoid the diagnostic term of LATE‐NC, based on current knowledge. Neuroanatomical regions of interest in LATE‐NC are specified factoring in neuropathologic data from different research centers.ConclusionLATE‐NC is a very common dementia, differentiable from ADNC or FTLD, and recent studies have refined our ability to make the diagnosis of LATE‐NC with increasing specificity. Areas needing additional study will be highlighted.