Retinal Alterations as Potential Biomarkers of Structural Brain Changes in Alzheimer’s Disease Spectrum Patients

Abstract

Retinal imaging being a potential biomarker for Alzheimer’s disease is gradually attracting the attention of researchers. However, the association between retinal parameters and AD neuroimaging biomarkers, particularly structural changes, is still unclear. In this cross-sectional study, we recruited 25 cognitively impaired (CI) and 21 cognitively normal (CN) individuals. All subjects underwent retinal layer thickness and microvascular measurements with optical coherence tomography angiography (OCTA). Gray matter and white matter (WM) data such as T1-weighted magnetic resonance imaging and diffusion tensor imaging, respectively, were also collected. In addition, hippocampal subfield volumes and WM tract microstructural alterations were investigated as classical AD neuroimaging biomarkers. The microvascular and retinal features and their correlation with brain structural imaging markers were further analyzed. We observed a reduction in vessel density (VD) at the inferior outer (IO) sector (p = 0.049), atrophy in hippocampal subfield volumes, such as the subiculum (p = 0.012), presubiculum (p = 0.015), molecular_layer_HP (p = 0.033), GC-ML-DG (p = 0.043) and whole hippocampus (p = 0.033) in CI patients. Altered microstructural integrity of WM tracts in CI patients was also discovered in the cingulum hippocampal part (CgH). Importantly, we detected significant associations between retinal VD and gray matter volumes of the hippocampal subfield in CI patients. These findings suggested that the retinal microvascular measures acquired by OCTA may be markers for the early prediction of AD-related structural brain changes.

Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort

“…Although multiple works have demonstrated a significant association between retinal structural changes (retinal nerve fiber layer (RNFL) and macular thinning mostly) and brain atrophy [ 59 – 64 ], few publications have focused on the specific relationship of retinal vasculature with brain structural changes. Similar to our results, Hu et al showed a positive association between retinal VD and gray matter volumes of the hippocampal subfields in 25 cognitively impaired patients (17 MCI and 8 AD dementia) [ 65 ].…”

Optical Coherence Tomography Angiography: Revolutionizing Clinical Diagnostics and Treatment in Central Nervous System Disease

“…FAZ area was lager in comparison to HC [10,29,37]. Researchers have also found that correlations between SRCP and disease duration [23], degree of cognitive impairment [23,36,42,49], and brain parenchymal volume [50] in AD patients continue to manifest. Biscetti et al found that the retinal FD is correlated with the CSF Aβ42/t-tau ratio [43].…”

“…Previous studies using OCT to observe retinal and choroidal thickness in patients with chronic migraine have found that migraine with or without aura cause varying degrees of impairment to the retinal structure and vascular system. The RNFL [50][51][52][53] and choroidal thickness [51,54] are significantly thinner in migraine patients compared to HC. A study using OCTA in migraine patients also found that choroidal thickness in migraine patients correlated with the disease duration.…”

Retinal Findings and Cardiovascular Risk: Prognostic Conditions, Novel Biomarkers, and Emerging Image Analysis Techniques

“…It must be noted that many of the imaging biomarkers discussed above are not specific to various forms of cardiovascular disease. For instance, many forms of dementia, such as Alzheimer's and Parkinson's Disease, have been associated with reduced vessel density in various layers of the retina when examined with OCTA [114][115][116]. Furthermore, parameters such as reduced vessel density in the various vascular layers of the retina are associated with multiple disease states of interest, such as chronic CVD (including hypertension and diabetes) and also acute stroke or MI risk.…”