Affiliations: [a] Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Medical School, Singapore | [b] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore | [c] Clinical Imaging Research Centre, The Agency for Science, Technology and Research and National University of Singapore, Singapore | [d] Department of Pharmacology, National University of Singapore, Singapore | [e] Memory Aging & Cognition Centre, National University Health System, Singapore | [f] Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
Correspondence:
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Correspondence to: Juan Zhou, PhD, Duke-NUS Medical School, 8 College Road, #06-15, Singapore 169857, Singapore. Tel.: +65 66012392; Fax: +65 62218685; E-mail: [email protected].
Note: [1] Joint first authors.
Note: [2] Joint senior authors.
Abstract: Both healthy and pathological aging due to Alzheimer’s disease (AD) are associated with decreased brain grey matter volume (GMV) and disrupted white matter (WM) microstructure. Thinner macular ganglion cell-inner plexiform layer (GC-IPL) measured by spectral-domain optical coherence tomography has been reported in patients with AD and mild cognitive impairment. Emerging evidence suggested a link between thinner GC-IPL and lower GMV in subjects with no dementia using region-of-interest-based approach. However, it remains unknown whether GC-IPL thickness is associated with brain WM microstructure and how such association differed between normal and cognitively impaired subjects. Here, for subjects with no cognitive impairment (NCI), thinner GC-IPL was associated with lower WM microstructure integrity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tracts, anterior thalamic radiation, and cingulum regions, while it was weakly associated with lower GMV in visual cortex and cerebellum. Nevertheless, these retina-brain associations were disrupted in the presence of cognitive impairment. Correlations between GMV and GC-IPL were lost in patients with cognitive impairment but no dementia (CIND) and AD patients. GC-IPL was related to WM microstructural disruption in similar regions with decreased significance. In contrast, lower WM microstructure integrity in the fornix showed a trend of correlation with thinner GC-IPL in both CIND and AD but not NCI. Collectively, our findings suggest the possible physiological retina-brain relationship in healthy aging, which might be disrupted by disease-induced changes in patients with cognitive impairment. Longitudinal study with larger patient sample should follow to confirm the disease mechanism behind these retina-brain relationship changes.
