Author’s Disclosure Block: Fei Wu, none; Monica Lavoie, none; Mélanie Hébert, none; Robert Laforce Jr, none; Ali Dirani, none

Abstract Body
Purpose: The logopenic variant primary progressive aphasia (lvPPA) is a rare neurodegenerative disorder which predominantly affects language functions. In 86% of lvPPA cases, the underlying pathology is amyloidopathy as seen in Alzheimer’s disease (AD). Similar to AD, the development of new treatments for lvPPA relies on biomarkers which could allow early diagnosis of this condition. While recent research has explored the use of optical coherence tomography (OCT) and OCT-angiography (OCT-A), two imaging modalities of the retina, as non-invasive biomarkers for AD, their potential in lvPPA remains unexplored. To the best of our knowledge, our work is the first study comparing retinal findings in lvPPA patients and healthy controls using OCT and OCT-A. Study Design: The design of this study is cross-sectional with prospective recruitment. Methods: From December 7, 2022, to March 7, 2024, participants with lvPPA and healthy controls matched for sex and age were enrolled. The selection criteria were preexisting neurological and eye conditions. For both participants with lvPPA and controls, an extensive ophthalmological assessment was performed to rule out eye diseases. Following OCT/OCT-A imaging, lvPPA patients also received a cognitive assessment (Clinical Dementia Rating, or CDR score) and a lumbar puncture to confirm the stage of their cognitive impairment and the underlying amyloidopathy, respectively. Results: Ten participants with lvPPA and eleven controls were enrolled. All patients had amyloidopathy confirmed by lumbar puncture, with a mean CDR global score of 0.55 ± 0.16 (mild dementia). Estimated mean temporal region retinal nerve fiber layer (RNFL) thickness was lower in the lvPPA group compared to controls (63.1 ± 3.3 vs 75.6 ± 3.2 μm, p = 0.013). The estimated average macular thickness was greater in the lvPPA group compared to controls (286.9 ± 3.5 vs 275.0 ± 3.3 μm, p = 0.022). Foveal avascular zone circularity (FAZ) was significantly lower in the lvPPA group compared to controls (0.69 ± 0.02 vs 0.77 ± 0.02, p = 0.002). Conclusions: Thinning of the RNFL may reflect retinal amyloid accumulation or transsynaptic retrograde degeneration in lvPPA. These mechanisms have previously been proposed to explain similar retinal findings in AD. The retrograde mechanism states that the amyloid-induced brain atrophy causes a lack of trophic factors from the brain, resulting in a retrograde (axon-to-neuronal-body) thinning of RNFL. Increased macular thickness might indicate an inflammatory response in early disease stages. Altered FAZ could signal early amyloid-induced vascular changes. Together, our findings suggest OCT and OCT-A could be valuable biomarkers for lvPPA.