UC Irvine

Background: Limbic predominant age related TDP-43 encephalopathy (LATE) is a newly proposed term to denote the contribution of transactive response DNA-binding pro-tein of 43 kDa (TDP-43) pathology to dementia at older age. The aim of this work was to study the role of LATE in cognitive impairment and its risk factors in the oldest old (those ≥ 90years old). Methods: 240 participants of The 90+ Study with comprehensive clinical, neuropsychology, and neuropathology data were included. Dementia status, clinical syndrome, and impaired cognitive domains were determined at multidisciplinary post-mortem case conferences blind to autopsy data. Alzheimer’s disease neuropathology (ADNP) was defined as CERAD neuritic plaque score≥2 and Braak neuro-fibrillary tangle stage≥5. We defined LATE as those with at least amygdala and hippocampal TDP-43 pathology (stage>2). We explored the association of LATE and of ADNP with cognition measures by logistic regression ana-lyses adjusting for age, sex, and education. We separately explored the association between medical histories (as potential risk factors) and LATE and ADNP as outcomes adjusting for the above covariates.