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.