ARVO 2025: Association between ocular and systemic mitochondrial diseases and dementia

At ARVO 2025, in Salt Lake City, Utah, Viha Vig, talked about her poster presentation investigating the relationship between mitochondrial eye and systemic diseases and Alzheimer's disease, vascular dementia, and other types of dementia

Video Transcript:

Editor's note: The below transcript has been lightly edited for clarity.

Viha Vig:

Hi everyone, Kia Ora and namaste. My name is Viha Vig. I'm from Bangalore, India originally. I did my undergrad in the United States in Boston in biochemistry molecular biology, and now I'm studying medicine. I'm in my final year in New Zealand.

Yeah, a little bit about my study. So the study that I'm presenting at the ARVO conference–we're investigating the relationship between mitochondrial eye and systemic diseases and Alzheimer's disease, vascular dementia, and other types of dementia. So this is one of the first studies in humans to investigate the relationship between mitochondrial diseases and different types of dementias. And what we found was that individuals–so this is a retrospective cohort based longitudinal study, and our results indicated that there was a higher prevalence of dementia. Highest in the ocular mitochondrial disease, than the systemic mitochondrial disease. In people with both those ocular and systemic mitochondrial disease had a much higher prevalence as well. And all three groups, ocular, systemic, and the combined mitochondrial disease group also had a pretty high incidence of all different types of dementia as well.
Another thing we found that ocular mitochondrial disease had a five times [more] increased risk of dementia compared to controls, whereas systemic mitochondrial diseases had three times [more] increased risk of dementia. And when someone has both those diseases, they have seven times [more] increased risk of dementia compared to controls. And then we went on to do time-to-event analysis, and generated some Kaplan-Meier curves, which showed us that people with mitochondrial diseases develop dementia at a much earlier age compared to controls who develop dementia around 65 or above. So people with mitochondrial disease spend a lot more of their life with dementia. Those were our results.

Now the clinical takeaway is that mitochondrial dysfunction is a part of the shared neuropathic physiology of dementia, different types of dementia as well as mitochondrial diseases. And we know some of this already. We use PET scans in our clinical practice as standard of care to detect dementia. The clinical application is that mitochondrial dysfunction can be used as biomarker or a target for pharmacological therapies to reduce cognitive decline, because mitochondrial dysfunction does happen before the onset of symptoms in dementia, and there's enough studies in the literature supporting this. Additionally, another thing that I thought we could do, which would be really cool, is if we can quantify the mitochondrial dysfunction in the retina through direct methods FLIM imaging or indirect methods like electroretinograms, then we have an idea of dementia progression over time and the pathology going on in the brain. Because the retina and the brain, they actually come from the same source, embryologically, so this would be like a much less expensive and less invasive way to detect dementia.

At the moment, there's two thoughts amongst the scientists who are investigating eye disease and dementia. One school of thought is focused on retinal neurodegeneration and vascular changes in the retina, and that directly correlates with what's happening in the brain. And that's a direct correlation. Another school of thought is a little bit of an indirect correlation. So these people think that vision loss–which is a very valid point–that vision loss leads to social isolation, which is a huge risk factor for dementia. So both these theories, I believe, are quite valid. I've been working on the first school of thought, like with retinal neurodegeneration, and looking at the brain like that. We've already published a lot of studies–I think we were one of the first research groups to detect neurofilament light chain in the vitreous, and we were also one of the first to detect amyloid beta, our research group, Aβ42/40, and Beta 181, which are Alzheimer's disease biomarkers, and neurofilament light chain is a neurodegeneration biomarker in the vitreous. So that was pretty cool. And I think, like, the future direction that this is going in is like, I think we need to develop better imaging.

So there's a person called Dr. Stephen Sinclair, who's, like, one of the oldest scientists and retina doctors in our industry. And he's developed this really cool fundus camera that looks beyond the retina, at the choroid, and the ischemic changes in the choroid. And I think that's one way to go, you know, to see if we can get a more definitive answer on the pathology of dementia. Because as of now, I do know that there's, like, a lot of missing gaps, even though information is increasing every day, and we're publishing things. There's still quite a few missing gaps. But I think cool technologies like that fundus camera that visualizes the vasculature of the choroid, and then the FLIM technology to quantify mitochondrial dysfunction, which you know correlates with new neurodegeneration in the brain, is, I think, the way to go and where the future is taking us.

When talking about the mitochondrial disease study, specifically, I think that it would be a really good target for pharmacological therapies, and because we already know that mitochondrial dysfunction, it has a huge role to play in dementia. That's a well established thing, and it's more well established in animal models. And mitochondrial dysfunction happens before the onset of symptoms of dementia. So it gives us a chance to reduce the rate of cognitive decline, and if I'm going to be ambitious, may also give us a chance to, you know, reverse dementia to an extent, but I think it'll mainly just reduce the rate of cognitive decline. To be honest.