Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer’s Disease

Article type: Research Article

Authors: Mathew, Sunu^a | WuDunn, Darrell^b | Mackay, Devin D.^a | Vosmeier, Aaron^{a; c} | Tallman, Eileen F.^{a; c} | Deardorff, Rachael^{a; c} | Harris, Alon^d | Farlow, Martin R.^{a; c} | Brosch, Jared R.^{a; c} | Gao, Sujuan^{a; c} | Apostolova, Liana G.^{a; c} | Saykin, Andrew J.^{a; c} | Risacher, Shannon L.^{a; c; *}

Affiliations: [a] Indiana University School of Medicine, Indianapolis, IN, USA | [b] University of Florida Health, Jacksonville, FL, USA | [c] Indiana Alzheimer’s Disease Research Center, Indianapolis, IN, USA | [d] Icahn School of Medicine, New York, NY, USA

Correspondence: [*] Correspondence to: Shannon L. Risacher, PhD, Assistant Professor of Radiology & Imaging Sciences, Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer Disease Center, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA. Tel.: +1 317 963 7513; Fax: +1 317 963 7547; E-mail: srisache@iupui.edu.

Abstract: Background:The eye has been considered a ‘window to the brain,’ and several neurological diseases including neurodegenerative conditions like Alzheimer’s disease (AD) also show changes in the retina. Objective:To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. Methods:75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. Results:Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes. Conclusion:RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.

Keywords: Alzheimer’s disease, brain volume, MRI, neurodegeneration, optical coherence tomography, retinal nerve fiber layer

DOI: 10.3233/JAD-210533

Journal: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 743-752, 2023