Retinal microvascular changes are related to indicators of glymphatic dysfunction and small vessel disease in frontotemporal dementia

INTRODUCTION: Retinal vascular alterations have been associated with cerebral small vessel disease (SVD) in frontotemporal dementia (FTD), but their relationship with magnetic resonance imaging (MRI)-derived glymphatic-related diffusion markers remains unclear. We investigated retinal vascular fractal dimension (FD) in relation to SVD, glymphatic-related diffusion metrics, and clinical measures. METHODS: Thirty-four patients with clinically diagnosed FTD (82.4% behavioral variant FTD) and 34 cognitively unimpaired controls underwent color fundus photography and multimodal MRI. Generalized estimating equations, multivariable regression, and partial Spearman correlations were performed. RESULTS: FTD showed sparser retinal microvasculature, lower diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), and periventricular diffusivity, and higher SVD burden (all p < 0.05). Sparser retinal microvasculature was associated with reduced DTI-ALPS, lower periventricular diffusivity, greater SVD burden, poorer cognition, and greater disease severity (all p < 0.05). DISCUSSION: Retinal microvascular alterations are related to SVD and glymphatic dysfunction in FTD.