Alzheimers - Prevention is Better than Cure

This news article highlights the problem of treating dementias. The relevant article from Nature can be found here.

Prevention is always better than cure. In relation to dementias it is now clear that years, if not decades, before symptoms arise a neurodegenerative process has been in play. As noted at the top of the news release, once alzheimers is established there probably is never going to be a cure. We may be able to forestall progression of pathology but that is all we will be able to do.

While it is tempting to think that alzheimers is all about the brain we must remember that the brain functions within a body. Our overall health is fundamental to cerebral health. Due to my lack of reading lately I can't be sure about all the relevant factors but the below list will serve as a useful guide:

• There has been a longstanding relationship between cardiovascular health and cerebral health. Maintaining good cardiovascular health is absolutely essential in addressing dementia. This appears to be particularly true for cholesterol and triglyceride levels. Keep check of these levels. Note however that for people over 60 there is evidence to suggest that slightly higher cholesterol levels are protective for the brain. Only slightly higher, the safer bet probably being higher but still within normal ranges.
• Immunological status is very important. Preventing excessive inflammation is very important for protecting the brain because systemic inflammations plays a cardinal role in promoting dementias. Diet is very important here, as is adequate vitamin D intake. Because many people lose the ability to manufacture vitamin D with age, and because dietary sources are usually of low quantities, supplementation is often a good idea. Before going down that road though have your vitamin D status checked. If it is low start taking supplements.
• Do not let low level infections linger. These promote systemic inflammation.
• Maintain oral health. Poor oral health is not only a risk factor for dementias but also heart disease. Again, systemic inflammation can arise from poor oral health.
• Maintain a appropriate fat intake. Keep the balance right. Avoid trans fats at all costs. Eat fish on a regular basis, watch your omega 3 - omega 6 balance because the modern diet tends to have too much omega 6 and too little omega 3, this promotes inflammatory mediators because omega 6 fats promote the generation of inflammatory prostaglandins while omega 3's promote anti-inflammatory prostaglandins. It is very important to cook fish the right way - baked or broiled, grilled and fried fish may actually promote dementias and heart disease because the high temperatures oxidize the fats.
• Be very careful about sugar rich foods. Sugar in strict moderation is fine but many processed foods are loaded with too much sugar. Popular carbonated drinks are sugar laden and should not be consumed as a habit.

Can Diet Reverse Alzheimers?

Hope springs eternal, except when you're dead. (With no Arrow of Time is one eternally dead or eternally alive? Or am I in a box and if God happens to look inside will my fate then be decided? God, don't look!) On the internet there is a cure and conspiracy for everything. Such is the nature of human cognition, a ramshackle attack on reality that through brute force manages to get enough things right amidst the a multitude of errors and disasters. I read Camus in another life and I really must try to start forgetting him.

If the only significant history of human thought were to be written, it would have to be the history of its successive regrets and its impotences.

The Myth of Sisyphus, page 24

I seriously doubt there can ever be a cure of Alzheimers. (At the end of this post though I do suggest one idea that is worthy of serious consideration.) By the time diagnosis is made the damage tends to be extensive. Take Parkinsons Disease as an example, the individual can lose up to 60% of the neurons in the substantia nigra before symptoms arise. In dementias generally, by time of diagnosis a vicious physiological cycle of destruction has become established and at present there is no obvious solution to that problem. There is an increasingly detailed understanding of these processes and in time it will be possible for individuals to institute strategies that can seriously arrest the progression of even advanced dementia; though at that stage of dementia I'd rather take a bullet than pills. Such treatment expectations however are for another generation.

In our time, studies like this point to strategies that *may* help us. All things considered, it will not be a matter of single strategies or golden elixirs, but rather a lifestyle that incorporates a variety of strategies to minimise the risk of dementia.

Marijuana and Dementia

Over the years there have been multiple studies indicating the potential of cannabinoids across a wide range of conditions. This latest study provides further weight as to the therapeutic potential of cannabinoids. It is high time that the public was made aware of the considerable therapeutic potential of these compounds. As for the psychosis\schizophrenia risk, that has been too much overblown and the risk is virtually negligible post 21 years of age. The reasons for this therapeutic potential are:

• The two principal cannabinoids, THC and cannabidiol, have very strong antioxidant capacity.
• These two compounds are lipophilic, that is lipid soluble, hence will remain in the body for extended periods. For pot smokers, typical wash out periods are 90% after one week, though this can greatly vary.
• Both of these compounds target specific receptors. THC will target CB1 and to a lesser extent CB2(controversial), while cannabidiol is very specific for CB2 and hence is non-psychoactive.
• Both compounds will bind to the anion site of ACHe, an enzyme that breaks down acetylcholine. This neurotransmitter is markedly reduced in some dementias, particularly Alzheimers.
• ACHe is also strongly implicated in amyloid production, both cannabinoids reduce the production of amyloid, an early step in Alzheimers because this production seems contingent on the anion site.
• Activation of the CB2 receptor limits the expression of pro-inflammatory cytokines, excess production of these cytokines being implicated in everything from atherosclerosis to cancer to dementia.

Vitamin B3 and Alzheimers Disease

9/11/2008 4:37PM

Vitamin B3 and Alzheimers Disease

Nicotinamide is a form of Vitamin B3. This is a promising study because this compound was found to target a key and early initiator of amyloid plaque formation in the brain. That process is tau phosphorylation which is implicated in many neurodegenerative conditions. Nicotinamide can be purchased as supplement and is generally safe but at very high doses can be toxic.

The Science Daily news release is available here.



The Journal of Neuroscience, November 5, 2008, 28(45):11500-11510; doi:10.1523/JNEUROSCI.3203-08.2008
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
Kim N. Green,1 Joan S. Steffan,2 Hilda Martinez-Coria,1 Xuemin Sun,3 Steven S. Schreiber,3,5 Leslie Michels Thompson,1,2,4 and Frank M. LaFerla1
Departments of 1Neurobiology and Behavior, 2Psychiatry and Human Behavior, 3Neurology, 4Biological Chemistry, and 5Anatomy and Neurobiology, University of California, Irvine, Irvine, California 92697-4545
Correspondence should be addressed to Frank M. LaFerla, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545. Email: laferla@uci.edu
Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated -tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability.