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The Role of Oxidative Stress in Alzheimer's Disease (Lifestyle changes do matter)
Posted: Thursday, May 7, 2015 5:13 PM
Joined: 9/13/2013
Posts: 112

George Perry on the Role of Oxidative Stress in Alzheimer's Disease

This in an interview in June 2011 with Dr George Perry, a self professed outlier in Alzheimer’s research. He rejects the amylod beta hypothesis of Alzheimers, and promotes oxidative stress hypothesis.

He suggested lifestyle changes as best way of half preventing AD. (see page 2 of article)

“Exercising, eating a proper diet, being socially involved, taking the advice your grandmother might have given you. All those types of lifestyle changes can reduce incidence by about half. It doesn't completely protect you, but that's the best we can do at this time.”

This lifestyle changes prevention is substantiated later by the FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability’) that is published by AAIC (Alzheimer’s Association International Conference) 2014 press release.

Some of our Message Board forum members have been actively adapting these lifestyle changes by what they called Best Practices.

Preventing oxidative stress by adapting lifestyle changes may well be the reason why forum members are able to arrest/maintain their cognitive ability, way beyond what the medical and research professionals have predicated about AD’s doom and gloom. It seems to be effective in stabilizing, maintaining or preventing cognitive impairment, whether EOAD and LOAD.


Here’s one study that is quite interesting – Dr Perry et al recommended the use of a combination of anti-oxidants to combat oxidative stress. (200

Antioxidant Therapy in Alzheimer’s Disease: Theory and Practice

A list of Dr Perry and associates’s current research endeavours towards oxidative stress hypothesis, for anyone who might be interested (2011 – 2013)

Lane Simonian
Posted: Friday, May 8, 2015 10:07 AM
Joined: 12/12/2011
Posts: 5140

Thank you for presenting the oxidative stress hypothesis for Alzheimer's disease in such a clear and insightful manner. Perry and his colleagues have been working on this for almost two decades, but have unfortunately received inadequate attention for their hypothesis (stated below).

For nearly 20 years, the primary focus for researchers studying Alzheimer disease has been centered on amyloid-β, such that the amyloid cascade hypothesis has become the “null hypothesis.” Indeed, amyloid-β is, by the current definition of the disease, an obligate player in pathophysiology, is toxic to neurons in vitro, and, perhaps most compelling, is increased by all of the human genetic influences on the disease. Therefore, targeting amyloid-β is the focus of considerable basic and therapeutic interest. However, an increasingly vocal group of investigators are arriving at an “alternate hypothesis” stating that amyloid-β, while certainly involved in the disease, is not an initiating event but rather is secondary to other pathogenic events. Furthermore and perhaps most contrary to current thinking, the alternate hypothesis proposes that the role of amyloid-β is not as a harbinger of death but rather a protective response to neuronal insult. To determine which hypothesis relates best to Alzheimer disease requires a broader view of disease pathogenesis and is discussed herein.

The Mediterranean diet which is part of Best Practices and which consists in large part of antioxidant polyphenols has been shown to slow the progression of Alzheimer's disease:

RESULTS: Eighty-five patients with AD (44%) died during the course of 4.4 (+/-3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence tertile, those at the middle tertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years' longer survival), whereas subjects at the highest tertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years' longer survival; p for trend = 0.003).


Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose-response effect.

The critical question is which antioxidants actually partially reverse Alzheimer's disease. The likely answer is methoxyphenols: eugenol, ferulic acid, syringic acid, sinapic acid, curcumin, and vanillin. The methoxy group increases the abstraction of hydrogen atoms which means that more peroxynitrites--the key oxidant in Alzheimer's disease--are scavenged. Hydrogen reverses oxidative damage and water (a product of peroxynitrite scavenging) reverses nitration damage. As a result, the blood flow in the brain increases, neurons are once again regenerated in the hippocampus, more glucose can be transported in the brain, and more neurotransmitters involved in short-term memory, sleep, mood, social recognition, and alertness are produced and released in the brain. Aromatherapy with essential oils high in eugenol (bay laurel, clove, lemon balm, cinnamon leaf, holy basil, rosemary, for instance) is effective because the eugenol has to pass through very little blood to get to the brain. Plants containing two or more methoxyphenols also appear to be effective (Panax ginseng).

What is needed is a survey of plants containing multiple methoxyphenols. Adina polycephela is one example of a plant which with further study might prove useful to the treatment of Alzheimer's disease.

We may still be looking for a needle in a haystack, but at least we know what we are looking for.