We report on three individuals with semantic variant primary progressive aphasia (svPPA) whose post-mortem pathology was consistent with diffuse neocortical Lewy body disease (LBD). We believe this is a heretofore unrecognized phenotype of LBD.

The present conception of primary dementias pairs clinical syndromes with neuropathologies, proven on necropsy or indirectly implicated by biomarkers. Each pairing is a clinicopathological entity. There is an increasing focus in the field of neurodegenerative disease to better characterize clinicopathological disorders, so as to target research and treatment approaches. SvPPA clinically manifests with progressive loss of semantic knowledge and is commonly associated with TDP-43 type C proteinopathy as well as Alzheimer's(AD) and other tau pathologies. We report on three instances of svPPA associated with LBD pathology. We believe this is the first such report in the literature.

Our institution's brain bank was queried for clinicopathological cases with a clinical diagnosis of svPPA and neuropathologic diagnosis of LBD. Three cases met the international consensus criteria for svPPA and were included in this study.

Three males aged 60-76 satisfied our inclusion criteria. Two subjects had significant temporal atrophy, and one had substantia nigral pallor. DAT scan was available in one subject, which was a negative study. All subjects fit the neuropathological consensus criteria for LBD with a diffuse neocortical distribution. In addition, all subjects had moderate vascular pathology and AD pathology (2-high ADNC, 1-intermediate). One case was also found with limbic associated Stage 1 TDP-43 proteinopathy.

Here we propose a novel language variant of Lewy body disease. Although rare, LBD should be included as a differential diagnosis in individuals with svPPA. In the future, characterizing phenotypes of LBD will assist in more precise targeting of research and treatment strategies.