34 patients with clinically diagnosed FTD (82.4% behavioral variant FTD) and 34 cognitively unimpaired controls were included
Retinal vascular fractal dimension (FD) was used as the measure of retinal microvascular density/complexity
Color fundus photography was used to assess retinal vasculature
Difference was statistically significant (p < 0.05)
Generalized estimating equations were used to compare groups
Results
FTD patients had lower DTI-ALPS (diffusion tensor imaging analysis along the perivascular space) values compared to controls, indicating glymphatic dysfunction.
DTI-ALPS is an MRI-derived glymphatic-related diffusion marker
Multimodal MRI was performed in all participants
Difference was statistically significant (p < 0.05)
Multivariable regression and partial Spearman correlations were used in analyses
Periventricular diffusivity is another MRI-derived glymphatic-related diffusion metric examined
Difference was statistically significant (p < 0.05)
This metric was assessed alongside DTI-ALPS as part of the glymphatic dysfunction indicators
Results
FTD patients demonstrated higher cerebral small vessel disease (SVD) burden compared to controls.
SVD burden was assessed using multimodal MRI
Difference was statistically significant (p < 0.05)
SVD markers were examined in relation to retinal microvascular changes
Results
Sparser retinal microvasculature was associated with reduced DTI-ALPS and lower periventricular diffusivity in FTD.
Associations were statistically significant (p < 0.05)
Analyses were performed using multivariable regression and partial Spearman correlations
This suggests a link between retinal microvascular changes and glymphatic dysfunction
Results
Sparser retinal microvasculature was associated with greater SVD burden in FTD patients.
Association was statistically significant (p < 0.05)
This finding extends prior work linking retinal vascular alterations to cerebral small vessel disease in FTD
Multivariable regression and partial Spearman correlations were used
Results
Sparser retinal microvasculature was associated with poorer cognition and greater disease severity in FTD.
Associations were statistically significant (p < 0.05)
Both cognitive measures and disease severity measures were examined as clinical outcomes
This links a non-invasive retinal measure to clinically meaningful outcomes in FTD
What This Means
This research suggests that changes in the tiny blood vessels of the retina (the light-sensitive layer at the back of the eye) are connected to two important disease processes in frontotemporal dementia (FTD): small vessel disease in the brain and dysfunction of the brain's waste-clearance system (called the glymphatic system). The study compared 34 FTD patients (most of whom had the behavioral variant of FTD) with 34 healthy controls using eye photography and specialized brain MRI scans. FTD patients had sparser retinal blood vessel networks, worse brain glymphatic function (measured by MRI markers called DTI-ALPS and periventricular diffusivity), and more small vessel disease in the brain.
Importantly, the sparseness of retinal blood vessels was not only linked to these brain imaging abnormalities, but also to worse cognitive performance and greater overall disease severity in FTD patients. This suggests that the retina — which can be examined non-invasively using standard eye imaging equipment — may reflect what is happening in the brain in terms of vascular health and waste clearance.
This research suggests that retinal imaging could potentially serve as an accessible, non-invasive window into brain health in FTD, offering a way to track disease-related vascular and glymphatic changes without requiring expensive or burdensome brain scans. However, the study was relatively small (34 patients), and further research is needed to confirm these findings and determine whether retinal measures could be useful as clinical biomarkers for FTD.
Kwapong W, Chen Y, Chen X, Hou J, Lu H, Xu Y, et al.. (2026). Retinal microvascular changes are related to indicators of glymphatic dysfunction and small vessel disease in frontotemporal dementia.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71844