Case report: A comprehensive neuropsychological assessment in a patient with limbic-predominant age-related TDP-43 encephalopathy.

OBJECTIVE: Limbic Predominant Age-Related TDP43 Encephalopathy (LATE-NC) is a recently defined (2019) degenerative transactive response DNA binding TDP43 proteinopathy whose prevalence increases after age 80, marked by an amnestic presentation. Anatomically, atrophy predominantly occurs in the hippocampal region, in a unilateral or bilateral manner, yet workup is negative for amyloid and phosphorylated tau (e.g. PET scan; cerebrospinal fluid). Postmortem immunohistochemical data revealing neurofibrillary tangles accumulation initially occurring in the limbic (e.g. amygdala) region with subsequent gradual diffusion throughout the brain in a hierarchical manner (e.g. hippocampus, entorhinal cortex, subcortical, cortical).

METHOD: Case report methodology focused on a 76-year-old, Black, right-handed male who presented with slowly progressive memory decline over the past year, in the context of a negative beta-amyloid PET result and MRI findings of bilateral hippocampal atrophy (left > right).

RESULTS: Neuropsychological assessment revealed a gentleman of above-average premorbid intellect who performed within normal limits on a cognitive screening measure, yet further assessment revealed prominent memory retrieval deficits with more notable learning and memory deficits seen with rising demands. He also displayed subtle executive (e.g. processing speed, problem-solving; fluency switching) deficits, along with basic construction weaknesses.

CONCLUSION: The relatively intact global cognition, with memory retrieval deficits and intact semantic fluency, in the context of negative amyloid PET scans, aligns with the neurocognitive profile indicative of LATE. Neuropsychologists should be aware of this newly defined neurodegenerative disorder. Neurocognitive assessment may play a pivotal role in distinguishing between degenerative diseases and allowing for tailored treatment options.