Vascular cognitive impairment and dementia (VCID), or vascular dementia (VaD), represents the second most common cause of cognitive impairment and a diagnostic challenge, in part due to the overlap with other dementia syndromes, including AD. The diagnosis of VaD, which is largely clinical, encompasses executive, visuospatial and/or memory dysfunction, among other cognitive aspects. There is a strong association with vasculopathy, including hypertension, hyperlipidemia and diabetes, which, through different mechanisms, ultimately lead to brain ischemia and degeneration
[19]. White matter lesions or hyperintensities (WML/WMH), lacunar infarcts, microinfarcts, cerebral microbleeds and hemorrhages are the MRI hallmarks of this condition
[20].
The retina is considered an extension of the cerebral tissue, and the study of its vasculature may reflect brain pathology. Therefore, OCTA is ideally suited to non-intrusively visualizing the functional microvascular changes which can be expected to be present in VaD. Indeed, it has been demonstrated that the flow density of the inner retinal layers might be a useful biomarker in differentiating vascular from degenerative dementia, as it correlates with the Fazekas scale but not with the presence of pathologic (Aβ, τ) proteins in the cerebrospinal fluid (CSF)
[21][22]. A systematic review by Zhang et al. also revealed an association between WMHs and lower VD values, complementing the findings of Wang et al., who found the VD of the SCP to correlate with both WMHs and cognitive scores in patients with cerebral small-vessel disease (CSVD)
[23][24]. Research in patients with subcortical vascular cognitive impairment (SVCI), a subtype of VaD, has shown lower capillary density (CD) values in the temporal RPC plexus as compared to healthy subjects. The researchers demonstrated that the CD values of the temporal and superior RPC quadrants were lower in the SVCI subgroup than in AD patients, a finding compatible with the potential use of this OCTA parameter as a differentiating biomarker. Furthermore, they noted a negative correlation between the RPC density and the CSVD score, an inherently important aspect of cognitive decline in VaD
[20][25]. In a different study, patients with CSVD had lower VD values in both their temporal macular SCP and RPC plexuses versus healthy controls
[24]. Of note, another recent study has shown VD to be significantly reduced in the DCP and RPC of healthy (i.e., cognitively normal) subjects with higher Fazekas scores as well, which highlights the potential of OCTA as an early biomarker
[26]. The hypothesis that retinal microcirculation parameters might serve as biomarkers in VaD is further supported by the finding that lower vessel skeleton density (VSD)—a measure of perfused retina in OCTA images—is correlated with worse clinical (lower visuospatial and executive cognitive functions) and anatomical findings in patients with small-vessel disease (SVD)
[21]. Specifically, visuospatial and executive cognitive functions and MRI findings related to cerebral perfusion and reactivity were found to be negatively affected. Cognitive function also appears to correlate with SCP density
[24]. In one case report of a patient diagnosed with post-stroke VaD, a thinning of the choroid and electrophysiology consistent with outer retinal dysfunction was observed, which is argued to be in contrast to the inner retinal pathology reportedly associated with AD
[27]. The underlying pathophysiological mechanism seems to be the expansion of the cerebral hypoperfusion to the choroidal circulation. However, additional research is required to supplement our knowledge of this case.
As VaD is inextricably linked to cerebrovascular disease (CVD), hereditary forms of CVD have fittingly been studied in the search for relevant retinal biomarkers. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has indeed been found to be associated with lower VD in the DCP, affected RPC plexus and even choroidal thinning
[22]. Similarly, another study suggests that the OCTA parameters of macular VD may be used as early biomarkers for Fabry disease, as these predict myocardial changes which might precede cognitive impairment
[28].