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A connection between degenerative eye diseases and Alzheimer's disease
Lane Simonian
Posted: Wednesday, August 8, 2018 8:42 PM
Joined: 12/12/2011
Posts: 4631


A  recent study found a connection between age-related macular degeneration, diabetic retinopathy, and glaucoma and Alzheimer's disease:

Over the five-year study, 792 cases of Alzheimer’s disease were diagnosed by a committee of dementia experts. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40 % to 50% greater  risk of developing Alzheimer’s disease compared to similar people without these eye conditions. Cataract diagnosis was not an Alzheimer’s disease risk factor.

“What we found was not subtle,” said Dr. Paul Crane, professor of medicine, Division of General Internal Medicine, at the UW School of Medicine. “This study solidifies that there are mechanistic things we can learn from the brain by looking at the eye.”

Here is the connection:

CONSEQUENCES OF OXIDATIVE STRESS IN AGE-RELATED MACULAR DEGENERATION

Role of nitric oxide, superoxide, peroxynitrite and PARP in diabetic retinopathy.

Oxidative Injury to Blood Vessels and Glia of the Optic Nerve Head in Human Glaucoma

Widespread peroxynitrite-mediated damage in Alzheimer's disease.

And the role of marijuana compounds, which are peroxynitrite scavengers, in the treatment of three of the four disease. (the evidence is still partially lacking for macular degeneration).

Marijuana Compound May Help Stop Diabetic Retinopathy [cannabidiol]

Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite [for glaucoma]

Marijuana compound may offer treatment for Alzheimer's disease, study suggests [THC]

The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer's disease.

 

There is a whole range of diseases in which peroxynitrite plays some role.  The relative lack of attention regarding the use of strong peroxynitrite scavengers to treat these diseases is a shame.


Lane Simonian
Posted: Wednesday, August 8, 2018 9:05 PM
Joined: 12/12/2011
Posts: 4631


Another interesting connection:

Examining the Link Between Osteoporosis Drugs and AMD

A study published in the August issue of the American Journal of Ophthalmology has suggested a link between the use of oral bis­phosphonates, often prescribed to help prevent osteoporosis, and wet age-related macular degen­er­ation.

The disproportionality analysis found reported odds ratios for developing macular degeneration of 3.82 (2.94-4.96) for alendronate, 2.40 (1.49-3.86) for ibandronate and 2.87 (1.58-5.19) for risedronate.

My mother who took Fosamax for about a year had the beginning of macular degeneration, a damaged esophagus, Alzheimer's disease, and near the end of her life an irregular heart beat--all the result of oxidative damage, partially caused by Fosamax itself.


Lane Simonian
Posted: Wednesday, August 8, 2018 9:57 PM
Joined: 12/12/2011
Posts: 4631


After all these years, I think that I have finally found the full reason why bisphosphonate osteoporosis drugs increase the risk of Alzheimer's disease.

The mevalonate biosynthetic pathway. nBPs [aminobisphosphonate drugs such as Fosamax] inhibit farnesyl pyrophosphate (FPP) synthase and lead to a build up of IPP [isopentenyl pyrophosphate].

 IPP does not induce down-modulation of the TcR.CD3 complex, which likely results in the highly sustained signaling and release of high levels of TNF-alpha.

Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha

IFN-gamma and TNF-alpha are involved during Alzheimer disease progression

TNF-alpha induces peroxynitrite-mediated depletion of lung endothelial glutathione via protein kinase C.

Glutathione [depletion]: a molecular whistleblower for Alzheimer’s disease

The possible role of peroxynitrite in Alzheimer's disease: a simple hypothesis that could be tested more thoroughly.

Now I know how a combination of high glucose levels and the drug Fosomax led to Alzheimer's disease for my mother.


Lane Simonian
Posted: Thursday, August 9, 2018 9:47 AM
Joined: 12/12/2011
Posts: 4631


Degenerative eye diseases and Alzheimer's disease are peroxynitrite mediated diseases and some of the botanicals (ginseng and cannabidiol, for instance) that can treat the former can also treat the latter.

Botanical compounds have been widely used throughout history as cures for various diseases and ailments. Many of these compounds exhibit strong antioxidative, anti-inflammatory, and antiapoptotic properties. These are also common damaging mechanisms apparent in several ocular diseases, including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy, cataract, and retinitis pigmentosa. In recent years, there have been many epidemiological and clinical studies that have demonstrated the beneficial effects of plant-derived compounds, such as curcumin, lutein and zeaxanthin, danshen, ginseng, and many more, on these ocular pathologies.


There is ample evidence indicating that different reactive oxygen species (ROS), for example, superoxide, hydrogen peroxide, and hydroxyl and peroxyl radicals, are produced in cells under normal and pathological conditions (). When the rate of ROS generation exceeds the capacity of antioxidant defense, there is consequential oxidative damage to DNA, proteins, and lipids. In the central nervous system (CNS), oxidative stress is implicated in mechanisms leading to neuronal cell injury in various pathological states. Recently, the term “nitrosative stress” has been used to indicate cellular damage elicited by reactive nitrogen species (RNS), which include nitric oxide (NO) and its congeners such as peroxynitrite and nitroxyl anion. Together, oxidative and nitrosative stresses are implicated in the pathology of many neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and stroke...Due to the diverse functional effects offered by many natural botanical compounds, there is widespread interest in considering them as possible therapeutics for treating AD patients (). Plant-derived compounds are generally safer to use as compared with synthetic drugs (). Since neuroinflammation and oxidative damage are observed in the brains of transgenic rodent models of AD, a number of studies have used these animal models to test the neuroprotective effects of botanical compounds.


MissHer
Posted: Friday, August 10, 2018 6:16 PM
Joined: 11/13/2014
Posts: 2193


My mom took Fosamax but not for very long. It did give her GERD. She does have visual agnosia and I believe that started before she had any alz symptoms (to us). I went to the eye clinic a  couple of years after she had laser surgery for cataracts. She claims something was wrong with her vision, but after her exam the Dr said that nothing changed. (strange) The visual hallucinations are awful for her. I'm so angry.
Lane Simonian
Posted: Saturday, August 11, 2018 12:47 AM
Joined: 12/12/2011
Posts: 4631


Thank you for responding, MissHer.  My mother took Fosamax for about a year.  They say the drug stays in your system for years afterwards.  I cannot remember exactly but I think it was about six years after my mother stopped taking Fosamax that she developed Alzheimer's disease.

I think my mother had acid reflux as well.  She would sit up on the side of her bed at night which later I thought was probably due to acid reflux.  She would sometimes have to spit for long periods of time which was probably a sign of damage to her esophagus due to taking Fosamax.

My mother had cataract surgery which improved her distance vision but worsened her reading vision.  Probably that is not what happened to your mother, though.

I don't know what to do for highly distressing visual hallucinations.  The only thing that I have found after all these years is the following:

https://www.dovepress.com/yokukan-san-a-review-of-the-evidence-for-use-of-this-kampo-herbal-form-peer-reviewed-fulltext-article-NDT

 


Lane Simonian
Posted: Saturday, August 11, 2018 10:30 AM
Joined: 12/12/2011
Posts: 4631


One of the components of kampo is Angelica.  Ferulic acid in Angelica archangelica and rice brain oil appears to have a positive effect on hallucinations (although visual hallucinations are not specifically mentioned) in dementia.

Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies.

Treatment with Feru-guard led to decreased scores on the Neuropsychiatric Inventory in 19 of 20 patients and significantly decreased the score overall. The treatment also led to significantly reduced subscale scores on the Neuropsychiatric Inventory ("delusions", "hallucinations", "agitation/aggression", "anxiety", "apathy/indifference", "irritability/lability" and "aberrant behavior"). There were no adverse effects or significant changes in physical findings or laboratory data.

Similar results were also achieved in Alzheimer's patients.  

The Oregon Health Science University is now conducting a trial for feru-guard for the treatment of dementia.  Results should be available some time next year.


Lane Simonian
Posted: Saturday, August 11, 2018 10:39 AM
Joined: 12/12/2011
Posts: 4631


This may be reaching too far, but perhaps something to consider.

Alendronate-induced auditory hallucinations and visual disturbances.

Abstract

A 79-year-old Caucasian woman who had been taking alendronate [Fosamax] 10 mg/day for over 2 years to prevent osteoporosis reported hearing "voices in her head" along with red-colored visual disturbances. These auditory hallucinations and visual disturbances began shortly after her regimen was changed from alendronate 10 mg/day to 70 mg once/week. Assessment of causality using the Naranjo and Jones algorithms revealed a "probable" and "highly probable" relationship, respectively, between this adverse drug event and the switch from daily to weekly alendronate therapy. Other bisphosphonates, such as etidronate and pamidronate, have caused both reversible and irreversible auditory, visual, and olfactory hallucinations beginning 2 hours--1 week after drug administration. The mechanism behind these adverse effects is unknown but is thought to be independent of calcium homeostasis. Clinicians should be aware of central nervous system toxicity as a rare but potential adverse effect associated with bisphosphonates.

All the other side effects of Fosamax (jaw necrosis, irregular femur breaks, esophagitis, dementia, and atrial fibrilation) are the result of oxidative stress, so perhaps hallucinations are the result of oxidative stress as well.


dolor
Posted: Saturday, August 11, 2018 12:45 PM
Joined: 11/9/2017
Posts: 308


Oh good god more pieces of the puzzle from hell fall banging into place. 


dolor
Posted: Saturday, August 11, 2018 12:49 PM
Joined: 11/9/2017
Posts: 308


And I'm so sorry for what your mom endured and sorry for your loss. 

My mom's situation sounds similar to yours. 

And now there's us.

I need to find a source, and in Florida, that's not likely to be a doctor. 


dolor
Posted: Saturday, August 11, 2018 12:52 PM
Joined: 11/9/2017
Posts: 308


Miss Her I know just what you mean. I'm enraged about the diseases and the incomptence of the medical community. You think it has anything to do with the fact that 2/3rds alz victims are women?
MissHer
Posted: Saturday, August 11, 2018 3:12 PM
Joined: 11/13/2014
Posts: 2193


Yes I sure am angry that everyone and his brother seems to be getting dementia. My stepdad and mom both had dementia and your darned right that something is up.
dolor
Posted: Wednesday, August 15, 2018 4:11 PM
Joined: 11/9/2017
Posts: 308


Miss Her, it is crazy. Doctors are referring it to an epidemic now. I'm angry that researchers are taking stabs in the dark about what causes and triggers it.

I suspect it is something very common, and there is a reluctance...about something.

Pesticides can cause Parkinsons. Umm, everything we eat is sprayed with pesticides.

And Monsanto finally lost its first lawsuit. I'm waiting for the dominoes to fall!

https://www.cnn.com/2018/08/10/health/monsanto-johnson-trial-verdict/index.html


Lane Simonian
Posted: Wednesday, August 15, 2018 5:50 PM
Joined: 12/12/2011
Posts: 4631


I thought of bringing this up, too.  Thank you, Dolor.

One of the ingredients in Monsanto Roundup--polyethoxylated tallow amine--causes nitration damage that is linked to non-Hodgkins lymphoma, multiple myeloma, and Alzheimer's disease.

In the present study, the effects on oxidative balance and cellular end points of glyphosate, aminomethylphosphonic acid (AMPA), and a glyphosate formulation (G formulation) were examined in HepG2 cell line, at dilution levels far below agricultural recommendations. Our results show that G formulation had toxic effects while no effects were found with acid glyphosate and AMPA treatments. Glyphosate formulation exposure produced an increase in reactive oxygen species, nitrotyrosine formation, superoxide dismutase activity, and glutathione (GSH) levels, while no effects were observed for catalase and GSH-S-transferase activities. Also, G formulation triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. Aminomethylphosphonic acid exposure produced an increase in GSH levels while no differences were observed in other antioxidant parameters. No effects were observed when the cells were exposed to acid glyphosate. These results confirm that G formulations have adjuvants working together with the active ingredient and causing toxic effects that are not seen with acid glyphosate.

Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B‐cell non‐Hodgkin’s lymphomas and multiple myeloma

Widespread Peroxynitrite-Mediated Damage in Alzheimer’s Disease

These findings provide strong evidence that peroxynitrite is involved in oxidative damage of Alzheimer’s disease. Moreover, the widespread occurrence of nitrotyrosine in neurons suggests that oxidative damage is not restricted to long-lived polymers such as NFTs, [neurofibrillary tangles] but instead reflects a generalized oxidative stress that is important in disease pathogenesis.

The great comedic actor Gene Wilder had non-Hodgkin's lymphoma and died from Alzheimer's disease.


MissHer
Posted: Saturday, August 18, 2018 3:04 AM
Joined: 11/13/2014
Posts: 2193


Parent's lived in the country surrounded by corn and soybean fields. Step dad Parkinson's with LBD and mom ALZ.