Cognition-Eye-Brain Connection in Alzheimer's Disease Spectrum Revealed by Multimodal Imaging

The connection between cognition, eye, and brain remains inconclusive in Alzheimer's disease (AD) spectrum disorders.

To explore the relationship between cognitive function, retinal biometrics, and brain alterations in the AD spectrum.

Prospective.

Healthy control (HC) (n = 16), subjective cognitive decline (SCD) (n = 35), mild cognitive impairment (MCI) (n = 18), and AD group (n = 7).

3-T, 3D T1-weighted Brain Volume (BRAVO) and resting-state functional MRI (fMRI).

In all subgroups, cortical thickness was measured from BRAVO and segmented using the Desikan-Killiany-Tourville (DKT) atlas. The fractional amplitude of low-frequency fluctuations (FALFF) and regional homogeneity (ReHo) were measured in fMRI using voxel-based analysis. The eye was imaged by optical coherence tomography angiography (OCTA), with the deep learning model FARGO segmenting the foveal avascular zone (FAZ) and retinal vessels. FAZ area and perimeter, retinal blood vessels curvature (RBVC), thicknesses of the retinal nerve fiber layer (RNFL) and ganglion cell layer-inner plexiform layer (GCL-IPL) were calculated. Cognition-eye-brain associations were compared across the HC group and each AD spectrum stage using multivariable linear regression.

Multivariable linear regression analysis. Statistical significance was set at p < 0.05 with FWE correction for fMRI and p < 1/62 (Bonferroni-corrected) for structural analyses.

Reductions of FALFF in temporal regions, especially the left superior temporal gyrus (STG) in MCI patients, were linked to decreased RNFL thickness and increased FAZ area significantly. In AD patients, reduced ReHo values in occipital regions, especially the right middle occipital gyrus (MOG), were significantly associated with an enlarged FAZ area. The SCD group showed widespread cortical thickening significantly associated with all aforementioned retinal biometrics, with notable thickening in the right fusiform gyrus (FG) and right parahippocampal gyrus (PHG) correlating with reduced GCL-IPL thickness.

Brain function and structure may be associated with cognition and retinal biometrics across the AD spectrum. Specifically, cognition-eye-brain connections may be present in SCD.

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