Summary: In cognitively healthy people with a genetic risk for Alzheimer’s, retinal changes have been associated with alterations in the entorhinal cortex, hippocampus, and lingual gyrus. Researchers say retinal changes can be used to track changes in brain structures associated with Alzheimer’s in those with genetic risk factors.
In subjects who are cognitively healthy but have a high genetic risk of developing Alzheimer’s, correlations have been demonstrated between the retina and various brain structures which suffer changes as a result of the disease, such as the entorhinal cortex, the lingual gyrus and the hippocampus.
This is the main conclusion of the research led by the Ramón Castroviejo Institute for Ophthalmological Research (IIORC) of the Complutense University of Madrid (UCM).
The novelty of the study, published in Alzheimer’s Research & Therapy, lies in the fact that for the first time it has examined the correlations between the retinal areas and the cerebral structures most affected in Alzheimer’s, a disease in which up to two decades can pass before the first appearance of symptoms.
“This means that the retina, which is an easily accessible tissue, may provide information on the state of the brain and the changes taking place in it”, notes Inés López-Cuenca, IIORC researcher and lead author of the work.
Participating in the research with UCM were the San Carlos Clinical Hospital and the Technical University of Madrid, as part of a COGDEM study.
Next step: studying vision
To carry out the research, a group of patients was included whose fathers or mothers suffered from Alzheimer’s and who had a mutation in their gene ApoE ɛ4, which predisposes them to suffer from the disease.
The IIORC gave them ophthalmological examinations, including Optical Coherence Tomography (OCT). These tests were then compared with those of the magnetic resonance imaging (MRI) carried out by the Neurological Service of the San Carlos University Clinical Hospital of Madrid, and resulting in measurements of more than 20 different brain structures from both hemispheres.
“We have seen that these participants already show changes in some areas of the retina measured with OCT, while the brain MRI is still normal”, says López-Cuenca.
As well as the structure of the retina, the UCM group is collecting data on patients’ eyesight, to discover how the visual network operates in these phases of the disease which are still asymptomatic.
About this Alzheimer’s disease research news
Original Research: Open access.
“The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer’s disease: an exploratory analysis” by Inés López-Cuenca et al. Alzheimer’s Research & Therapy
The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer’s disease: an exploratory analysis
Two main genetic risks for sporadic Alzheimer’s disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD.
We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH−) and noncarriers of ApoE ɛ4 (ApoE ɛ4−) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+).
We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found.
In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.