Normal Tension Glaucoma and AD

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SGW811
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Normal Tension Glaucoma and AD

Post by SGW811 »

I am wondering if anyone else here, particularly among my fellow 4/4s, has been diagnosed with normal tension glaucoma. I was diagnosed two years ago, at age 53. I do have glaucoma in my family, but it is the typical, high pressure glaucoma. Normal tension glaucoma is rare. I have found some research from recent years suggesting that normal-tension glaucoma may signal the beginning of brain pathology similar to that of AD. My opthamologist is a neuro-opthamologist and he looked into this for me about a year ago, and informed me that the research is in its infancy and not conclusive, but I do worry about the potential connection, which makes sense to me -- normal-tension glaucoma is a diagnosis by process of elimination because there is no known cause, but compromised blood flow to the optical nerve may be a factor. Since I started treatment (latanaprost, to lower the pressure in the eyes) for the glaucoma, my condition has been stable, with no signs of further damage to the optical nerve. I have no other symptoms suggesting any cognitive dysfunction but the thought that this glaucoma could be an early signal of impending AD is unsettling, to say the least.
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Julie G
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Re: Normal Tension Glaucoma and AD

Post by Julie G »

SGW811, you've got my attention. I don't have the same condition, but glaucoma is on my radar as I've yielded elevated intraocular pressure on my last two eye exams. My ophthalmologist assures me that this isn't true glaucoma in my case because my corneas are thicker than normal. Apparently, the thickness of the cornea can provide false IOP readings.

Here's a recent paper that I've stumbled on, associating E4 with glaucoma. The authors hypothesize that it's our reduced lipid handling that may be involved. If I'm understanding correctly, higher HDL may be protective especially for our genotype as it enhances reveres cholesterol transport and helps attenuate peroxidation.
APOE4 has been associated with an elevated risk of developing POAG (Al-Dabbagh et al., 2009; Liao et al., 2014; Wang et al., 2014). Although the mechanism accounting for POAG susceptibility for APOE ε4 carriers is unknown, it is known that APOE4 appears to carry lipids less efficiently than APOE3 (Gong et al., 2002). In vitro, APOE3 is 2.5–3.9-fold better at promoting lipid efflux from astrocytes than APOE4 (Minagawa et al., 2009). It is possible that lipid trafficking plays a role in disease. In patients given supplemental DHA, the APOE4 allele was associated with less DHA in the cerebrospinal fluid than other alleles (Yassine et al., 2016). Thus, APOE4-bearing individuals may have limitations in lipid management.
Apolipoproteins cooperate with ABCA1 and other proteins to manage lipids. HDL is a major carrier of lipid hydroperoxides (Bowry et al., 1992), but they are more than just vehicles to support lipid trafficking. HDLs catalytically reduce cholesteryl ester hydroperoxides and phosphatidylcholine hydroperoxides (Garner et al., 1998). The APOAI and APOAII catalyze a two electron reduction of lipid hydroperoxides to their corresponding hydroxides. This step is particularly important because lipid peroxides damage membranes and promote LPP activity.
SGW811
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Re: Normal Tension Glaucoma and AD

Post by SGW811 »

Julie G., thanks for sharing this paper. I've been trying to follow this issue since I discovered my 4/4 status on the heels of my unexpected normal-tension glaucoma (NTG) diagnosis. It struck me right away that there might be a connection between this kind of glaucoma (which is otherwise unexplained) and AD. My neurologist poo-pooed the idea when I first raised it, but I decided to research it for myself. There are many articles and studies online. As I said, all are inconclusive, but the weight of opinion seems to be shifting to hypothesizing and/or finding a connection. Here are some recent articles and/or research I've found on the issue.

article framing the issue:
viewtopic.php?p=53894#p53894

recent study finding lower cognitive functioning for NTG patients:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678334/

common pathology of NTG and AD:
https://www.ncbi.nlm.nih.gov/pubmed/29210654

It appears to me that the medical consensus is that NTG, which causes are unknown but may be due to insufficient blood flow to the optic nerve, differs from glaucoma known to be caused by high intraocular pressures. However, I have seen at least one article arguing that there is no reason to separate NTG from "normal" glaucoma, and that it is all part and parcel of the same disease. That argument is that some people, like me, with glaucoma despite pressures in the "normal" range, have particularly fragile optic nerves that sustain damage even at these "normal" pressures. This article noted that NTG is typically seen in patients with pressures at the high end of normal (which is up to 21). At the time I was diagnosed, my pressures were at 19 and 18, so definitely at this higher end.

I would never have suspected that I had glaucoma at age 53, despite my family history. Fortunately my excellent opthamologist could readily see the damage to my optical nerve upon examination. I guess my cautionary tale to my fellow 4/4s and 3/4s is to get an annual eye exam by a qualified opthamologist and to be aware that glaucoma can be present, and cause irreversible damage, despite normal pressures. If we e4s are indeed more prone to it, than eye health is another area where we must be vigilant. I put off going to the doctor for years because I hated the long wait (my doc always runs an hour or more late past appointment time) and I hated the exam itself. Had I not waited, my NTG might have been detected earlier, before I already had lost some peripheral vision.
Orangeblossom
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Re: Normal Tension Glaucoma and AD

Post by Orangeblossom »

Interesting that E4 may have a link to glaucoma. and HDL may be protective. I remember my granny had both glaucoma and dementia in later years.
Roamingseer
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Re: Normal Tension Glaucoma and AD

Post by Roamingseer »

Thanks for the question. In early 2015 (age 57, E3/E4), my oculist identified potential NTG, which to this point i’m considered a glaucoma candidate w/ iops of 12/12. About a year ago, i saw a video & read a research paper where people receiving 50mg/d of black currants had increased blood flow in the eyes that arrested the worsening of their glaucoma, see https://nutritionfacts.org/video/dietar ... -glaucoma/. I decided to follow that regimen with 4oz of frozen blueberries a day. My last exam revealed no worsening of my condition.
chrissyr
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Re: Normal Tension Glaucoma and AD

Post by chrissyr »

Apparently this may be true for me, normal tension but a "glaucoma suspect". When I looked it up, Mayo Clinic site mentioned that less blood supply or atherosclerosis may be a culprit. Which of course immediately made me search APOE4.info! Thanks for the articles, and sure I'll add some currants or blueberries in!

I am more afraid to what decreased blood supply and atherosclerosis might be doing to the rest of my brain!

Thanks for posting, and I agree about eye health checks! It's a sneaky one with no symptoms at the beginning.
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