Cognitive Stages Leading to Dementia Appear Linked With Differences in Retinal Vasculature

Alzheimer dementia and mild cognitive impairment (MCI) were found to be associated with significant differences in retinal vasculature in peripheral regions of the retina, according to a study published in Translational Vision Science & Technology. Microvascular abnormalities in patients with Alzheimer dementia and MCI were compared with those with normal cognition, and differences in vasculature were observed among each stage.

Abnormalities in the eye are thought to indicate the deterioration of microvascular health and neuroaxonal degeneration of the brain due to the relationship between the retina and brain. About 35% of all patients who have a diagnosis of MCI will see a progression to Alzheimer disease within 5 years. This study aimed to find if an association existed between Alzheimer dementia or MCI with retinal changes in both the central and peripheral regions of the retina compared with participants with normal cognition.

Participants were recruited from the Duke Memory Disorders Clinic if they were aged 50 years or older and had a diagnosis of Alzheimer dementia or MCI. Participants with normal cognition were also recruited from the clinic if they were 50 years or older.

Participants were excluded if they had non-Alzheimer dementia, diabetes, demyelinating disorders, age-related macular degeneration, glaucoma, uncontrolled hypertension, visual acuity of worse than 20/40, or prior intraocular surgery other than cataract surgery. All participants needed to complete a Mini-Mental State Examination to evaluate their cognitive function.

All participants had ultra-widefield (UWF) imaging performed at the Duke University Memory Disorders Clinic, in which all images underwent stereographic projection to account for the curve of the eye. Images that did not have optimal projection were not used for analyzing distance measures but instead were used for evaluating the branching complexity of the eye. A custom software was used to measure the retinal vasculature.

UWF images were also included in a multifractal analysis to analyze the fractal dimension (FD) of the vessel branching patterns. Changes in width gradient (WG) and tortuosity was evaluated by splitting the images into quadrants.

The researchers used 165 images from 28 participants for the analysis of retinal vasculature. There were 43 eyes with Alzheimer dementia, 45 eyes with MCI, and 77 normal cognition eyes. Participants in the Alzheimer group were slightly older than the control group (mean, 73.1 vs 67.5 years). Retinal vessel WG and tortuosity analysis included the aforementioned eyes but excluded participants who did not have an accurate stereographic projection. Participants were still older in the Alzheimer group compared with the control group (mean, 71.8 vs 66.5 years).

Retinal vascular branching was found to be sparser in participants with MCI after analysis of the FD measurements; participants with Alzheimer disease had more complex arrangements of vessels compared with participants in the MCI and control groups. Higher FD in the midperiphery region of interest was found in participants with a diagnosis of Alzheimer dementia, which indicated a more complex branching complexity compared with the control group (β = 0.01) and the MCI group (β = 0.02).

Increased rates of arteriole and venule thinning was found to be significant in participants with Alzheimer dementia (β = –0.07) and MCI (β = –0.6) compared with the control group when WG was measured in all participants. A higher rate of venular thinning was found in Alzheimer dementia and MCI, which was significant in the MCI group (β = –0.5) compared with the control group.

A lower arteriole WG was found in the inferonasal quadrant compared with participants in the control group (β = –1.0). An increase in venular WG was found in the Alzheimer dementia group in the inferotemporal quadrant (β = –0.7) compared with the control group. The mean (SD) arteriole tortuosity was also higher in participants in the MCI group (–4.6 [0.4]) compared with participants in the Alzheimer dementia group (–4.6 [0.2]) and the control group (–4.6 [0.3]). Mean venular tortuosity was lower in participants with Alzheimer dementia compared with participants with a diagnosis of MCI or the control group.

There were some limitations to this study. Sample sizes were smaller and unknown compounding factors may exist. Some caution should be placed with the lack of associations for some measurements. Fluctuating accuracy and reliability of vascular measures should be considered.

The researchers concluded that small but significant retinal differences exist in participants with Alzheimer dementia and MCI, specifically in vessel branching and vessel thinning in those 2 groups compared with people of normal cognitive function.

Reference

Pead E, Thompson AC, Grewal DS, et al. Retinal vascular changes in Alzheimer’s dementia and mild cognitive impairment: a pilot study using ultra-widefield imaging. Transl Vis Sci Technol. 2023;12(1):13. doi:10.1167/tvst.12.1.13