Recognizing biomarkers of Alzheimer Disease using OCTA

A new optical coherence tomography angiography (OCTA) study¹ found distinctive microvascular signatures associated with various stages of decline in cognition, according to Yi Zhang, PhD, and associates. Zhang is from the Department of Bioengineering, University of Washington, Seattle.

The investigators explained that while Alzheimer disease can be diagnosed via positron emission tomography, magnetic resonance imaging, and cerebrospinal fluid biomarker analysis,^2-10 these approaches can be “costly, invasive, and operationally complex, restricting their feasibility for population-level screening or repeated longitudinal monitoring.^2,4,6-8,11 This creates a crucial need for scalable, noninvasive, and cost-effective methods that can identify early neurodegenerative or microvascular abnormalities.”12

For these reasons, they turned to the retina, which provides “a unique window into neurodegenerative pathology.”

“OCT/OCTA systems are widely available in ophthalmic clinics, require far less specialized infrastructure, and exhibit excellent repeatability, making them promising candidates for scalable cognitive assessment,²” and the rapidly obtained, three-dimensional images capture high-resolution pictures of the retinal, choroidal, and choriocapillaris structures and perfusion,^13,14 they explained.

OCTA study methodology

Zhang and colleagues conducted a cross-sectional study to determine if retinal, choroidal, and choriocapillaris biomarkers seen on OCTA images differed across cognitive states and if they can be used to differentiate among normal cognition, mild cognitive impairment, and Alzheimer disease dementia.

The study included 103 individuals broken down as follows: 49 control individual who were cognitively normal, 29 who were mildly impaired, and 25 with Alzheimer disease dementia. All participants underwent swept-source OCTA.

The main outcomes were the cognitive status, retinal vessel skeleton density, choriocapillaris flow deficit, and ganglion cell complex thickness, the investigators recounted.

What did the OCTA images show?

The participants were a mean age, 74.8 years.

Zhang and colleagues reported that the adjusted mean ganglion cell complex was thinner in individuals with Alzheimer disease compared with controls (63.31 μm and 67.93 μm, respectively), a difference that reached significance (P = 0 .03).

The adjusted mean choriocapillaris flow deficit was lower in those who were mildly cognitively impaired compared with those with Alzheimer disease (8.12% vs 9.07%, respectively), which also was significant (P = 0 .01); however, the value was higher in Alzheimer disease compared with controls (8.33%; P = 0.04).

Multivariable analyses showed that the following variables were associated significantly with cognitive status: the retinal vessel skeleton density in individuals who are mildly impaired and those with Alzheimer disease (P < 0 .001) and the choriocapillaris flow deficit in individuals who were mildly impaired and those with Alzheimer disease (P < 0 .001).

The investigators concluded, “The retinal vessel skeleton density and choriocapillaris flow deficit emerged as having associations with cognitive impairment, with the choriocapillaris flow deficit demonstrating a biphasic trajectory that may reflect early compensatory and later degenerative microvascular changes.”

They offered the following caveat, “Although the observed patterns suggest directions worth exploring, this study was not designed or powered to establish clinically actionable thresholds or generalize to the broader dementia population, and all findings should be considered preliminary.”

They emphasized the need for larger and longitudinal studies to determine the prognostic value and establish OCTA as a clinical tool to detect cognitive impairment early and monitor it.

References
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