To compare alternation of retinal microcirculation within the macula and optic disc in patients with dementia, mild cognitive impairment (MCI), and cognitively healthy subjects who had positive amyloid biomarkers (Aβ +) or not, using optical coherence tomography angiography (OCTA).

Alzheimer disease dementia (ADD) is the most common neurodegenerative disease dementia in elderly population associated with the accumulation of beta-amyloid (Aβ) plaques and tau neurofibrillary tangles (NFTs). Diagnostic biomarkers reflecting underlying amyloid or tau pathology of ADD have actively been developed. Of these, amyloid or tau positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) Aβ1-42 or phosphorylated tau are representative biomarkers for ADD. However, these tend to be expensive, invasive, or available only in a tertiary hospital or a specialized laboratory. Alternative biomarkers which are inexpensive, less invasive, and highly available could be needed.

Patients with ADD commonly show visuospatial dysfunction which is mainly attributed to damage of parieto-occipital or temporo-occipital visual pathway. In addition, previous studies using optical coherence tomography (OCT) which is a useful tool measuring retinal nerve fiber layer thickness (RNFLT), macula ganglion cell/inner plexiform layer thickness (GC/IPLT) reported impaired pregeniculate afferent visual pathway, for example, reduction of RNFLT and loss of retinal ganglionic cells (RGCs) in patients with ADD.

The retina and brain have the same embryological origin. These were branched off from the forebrain, so the brain and retina have similar anatomic and physiologic traits of the vasculature. In line with this, several studies using laser doppler ultrasonography, or retinal function imager (RFI) revealed narrowed central retinal vein and decreased its blood velocity, or low blood flow rate of retinal arterioles and venules in patients with mild cognitive impairment (MCI) and ADD. The authors suggested that in patients with ADD, accumulation of Aβ in the vessel walls could cause disruption of basement membrane and endothelium, leading to the decreased vascular lumen and density of retinal vessel. Indeed, postmortem study revealed accumulated Aβ inside or around RGCs in AD.

OCTA can clearly visualize not only the specific layers of retinal vasculatures, including superficial, middle, and deep capillary plexuses, but also choroidal vessels with a high resolution and in a reproducible manner, without contrast agent. A few prior studies using OCTA reported enlarged foveal avascular zone (FAZ) and decrease of retinal vascular density and choroidal thickness in ADD or MCI compared to controls. On the other hand, the others showed no differences in FAZ area and vessel density between them.

In this study, the investigators first evaluated structural and microvascular changes of retina and the microvascular change of macula and optic disc in patients with clinically diagnosed ADD, MCI and cognitively normal controls using OCT and OCTA. Then, to investigate whether impaired pregeniculate visual pathway is truly associated with underlying amyloid pathology, the investigators further investigated those OCT and OCTA parameters in each subgroup with positive or negative amyloid biomarker.

Inclusion Criteria:

• Clinical and pathologic diagnosis of ADD or MCI as well as cognitively unimpaired control (CU) from the Neurologic Clinic of Pusan National University Hospital

Exclusion Criteria:

• Patient not within the ages of 50-90 years old
• Patient with glaucoma, macular degeneration, retinal vascular disease including diabetic retinopathy, retinal vein occlusion
• Intraocular pressure (IOP) ≥ 21 mmHg
• Dense corneal or ocular media opacity
• History of ocular trauma or associated ocular disease
• Astigmatism ≥ 3.0 diopter or spherical equivalent ≥ 6.0 diopter
• Best corrected visual acuity (BCVA) < 20/40
• Any ocular surgery except uncomplicated cataract extraction
• Uncontrolled hypertension and diabetes

Neurologic Clinic of Pusan National University Hospital