Investigating ocular biomarkers and differential diagnosis of Alzheimer's disease and vascular cognitive impairment based on multimodal imaging

Significance: The eye can be used as a potential monitoring window for screening, diagnosis, and monitoring of neurological diseases. Alzheimer's disease (AD) and vascular cognitive impairment (VCI) are common causes of cognitive impairment and may share many similarities in ocular signs. Multimodal ophthalmic imaging is a technology to quantify pupillary light reaction, retinal reflectance spectrum, and hemodynamics. This provides multidimensional ocular metrics from a non-invasive approach to ocular biomarkers and differential diagnosis of AD and VCI.

Aim: We aim to investigate the changing pattern of ocular metrics in patients with AD and VCI using multimodal ophthalmic imaging.

Approach: Patients with subjective cognitive complaints in the memory clinic were subdivided into AD, VCI, and cognitively healthy individuals using neuropsychological and neuroimaging examinations, including positron emission tomography. All subjects underwent a medical history review, blood pressure measurement, medical optometry, intraocular pressure measurement, and custom-built multimodal ophthalmic imaging. Multidimensional parameters were analyzed by one-way analysis of variance and post hoc comparisons.

Results: This study included 19 patients with AD, 24 patients with VCI, and 37 cognitively healthy age- and sex-matched subjects. Both AD and VCI patients showed abnormal pupillary light reactions, including decreased resting pupil diameter, pupil constriction amplitude, and maximum constriction velocity. Compared with the control group, the AD group presented increased retinal reflectance at 548 nm, whereas the VCI group presented an increased resistivity index and decreased blowout score in retinal hemodynamics.

Conclusions: We demonstrate that pupillary light reaction-related neurodegeneration is the common pathological change in both AD and VCI. In addition, AD is characterized by alterations in retinal spectral signatures, whereas VCI is characterized by alterations in retinal hemodynamics. These findings suggest that multimodal ophthalmic imaging may have the potential to be used as a screening tool for detecting AD and VCI.