» Alzheimer’s Prevention – New Hope Rising

Prior to 2014 the dominant opinion in the medical community was that Alzheimer’s disease (AD) and most other forms of dementia, and their related symptoms, could not be prevented let alone reversed. However, in 2014 and 2015 this gloomy picture was finally dispelled with the following revelations.

The Karolinska/FINGER Preliminary Findings

In my August 2014 Newsletter I reported on the July International Conference on Alzheimer’s Disease in Stockholm. At that conference Dr. Miia Kivipelto from the Karolinska Institute in Sweden electrified the crowd with her blockbuster report on the Finnish Geriatric (FINGER) Intervention Study to Prevent Cognitive Impairment and Disability.[1] This ongoing study involves more than 1200 seniors at high risk for Alzheimer’s. These participants were already experiencing cognitive impairments.

The results from the first 2 years of this large controlled study showed that improvements in lifestyle including physical and mental activities, a healthy diet and social support had a significant beneficial effect on the participant’s cognitive performance. While those in the placebo group, who sought medical treatment as usual, continued their decline, those in the experimental group experienced, on average, a 35% improvement in memory. Executive function was 83% high than placebo, and processing speed a whopping 150% better than those who received standard medical treatment alone.

In her presentation, Dr. Kivipelto stated, “These findings show that prevention is possible, and that it may be good to start early,” noting that “With so many negative trials for Alzheimer’s drugs reported lately, it’s good that we may have something that everyone can do now to lower their risk.”[2]

What was so impressive about this study was the fact that they didn’t just improve health or reduce risk in healthy individuals, they actually reversed symptoms and effected improvements in individuals already in cognitive decline or well on their way to Alzheimer’s.

Korean Confirmation 

In October an article that appeared in the journal Psychotherapy and Psychosomatics corroborated this finding in a similar elderly lifestyle study conducted in Korea.[3]  Once again those who improved their diet and lifestyle showed improved cognitive function, and thus reduced risk for dementia.

But what about those already diagnosed with Alzheimer’s? Is it too late for them, or is escape from death by Alzheimer’s still possible at that stage?

UCLA Study Astounds Skeptics

Earlier in October 2014 we reported on a truly remarkable and encouraging paper published online in the new open access scientific journal AGING.[4]   This report described a “novel,” personalized therapeutic program for individuals diagnosed with significant cognitive impairment or Alzheimer’s. This treatment plan was developed by Dale E. Bredesen, MD at the Mary S. Easton Center for Alzheimer’s Disease Research at the University of California in Los Angeles. The protocol was based on what we know about the underlying causes of dementia.

Like the Korean and Finland (FINGER) study, it involved multiple modalities “designed to achieve metabolic enhancement for neurodegeneration (MEND).”[5] In other words it was a multifaceted approach focused on addressing various factors affecting brain health. However, this program was more rigorous and included hormones, and specific nutritional interventions to address cell metabolism, circulation and inflammation, as well as meditation, and other brain stimulating activities – like daily reading and brain games.

Dr. Bredesen notes that ”Based on the hypothesis that AD results from an imbalance in an extensive plasticity [ever changing] network, the therapy should address as many network components as possible, with the idea that a combination approach may create an effect that is more than the sum of the effects of many monotherapeutics.” (A synergistic effect.) Dr. Bredesen identified at least 36 things that can be out of balance in Alzheimer’s or other types of dementia, but fortunately most of these can be rectified by simply applying what we already know.

The point here is that there are many things that can go wrong and contribute to cognitive decline, and every “body” is different. But Dr. Bredesen notes that most of these precursors to AD, like diabetes and heart disease, can be prevented or overcome by the individual targeted application of existing knowledge in those fields. So, although most people with cognitive impairments have some things in common, a personalized program for each individual, focused on their particular issues and needs, will likely be best.  At least that is the approach Dr. Bredesen took with the 10 initial participants in his study. And amazingly 9 out of the 10 subjects with significant cognitive impairments, including several with diagnosed AD, improved! The only one who did not improve was in the later stages of Alzheimer’s.

Dr. Bredesen, being an MD, was able to employ a broader array of interventions than those used in the FINGER study, including medications and hormone replacement to address related disorders. But most of the interventions he used like dietary changes, meditation, periodic fasting, mental and physical exercise, as well as various nutritional supplements, are available to most anyone in the US without prescription.

The Joint International Review of AD Research

Also in 2014 an international investigation appeared which was conducted by some of the best and brightest Alzheimer’s researchers in the world – from France, the Netherlands, and the United States. It was a massive review of the more than 3,000 studies from around the world on diet, nutrition and brain health.[6]

In short, what they found in this monumental review was that nutritional deficiencies play a major role early on in the development of Alzheimer’s. This was a major revelation to many, with huge implications for the prevention and management of Alzheimer’s, as you will see below

Moreover, contributing factors included not only what they ate, i.e. how nutritious the foods were that they ate, but how well they digested and absorbed the nutrients from the foods they ate, as well as, changes in metabolism, and nutrient depletion due to their body’s “increased utilization of nutrients” needed to fight off disease and other issues incidental to aging.  So even if a person ate well, they could still end up with nutritional deficiencies, due to age, genetics and other unique biological factors exacerbated by age.

This then set the stage for what might be the most significant and hopeful study yet in the battle to prevent or arrest Alzheimer’s disease.

January 2015 – Even Greater Help and Hope

Finally on January 7th 2015 the Journal of Alzheimer’s Disease offered online to subscribers, an advanced copy of the UMass-Lowell study  I was involved in, on the effects of the NF (nutraceutical formulation now sold under the name Perceptiv™ ) on 106 individuals with diagnosed Alzheimer’s.[7]

Unlike the UCLA project, this was not a pilot or preliminary study, but a “gold standard,” double-blind, placebo-controlled, multi-site, phase II clinical study of the effects of a nutritional supplement, containing a variety of vitamins and other nutrients, on mental abilities associated with Alzheimer’s. This was the sixth successful clinical study with this formulation, which was developed over the past 20 years by Dr. Thomas Shea and colleagues at UMass-Lowell.
Basically, the study showed statistically-significant improvements or arrested decline in memory and other cognitive abilities (as measured by live standardized tests) in subjects diagnosed with Alzheimer’s who received the supplement, as compared to subjects who received a placebo.

(If you would like an uncorrected pdf “authors” copy email me at David@ABCbrain.org.[8] )

Here are the outcome highlights.
EPSON scanner image
Results after 3 months. The Clox test measures spatial abilities, reasoning and memory. The DRS is the Dementia Rating Scale which measures a variety of mental abilities. The AMSS adjusts for age and the AEMSS for age and education level. The forth chart shows the memory subscale. The dark block is where most of the scores fell. The thin line shows the range from highest to the lowest in ea category.

As you can see on each of these graphs, although the scores varied widely, after 3 months, the majority of those in the NF group, taking the Nutraceutical (nutritional) Formulation, performed significantly better on these tests of attention, memory, reasoning, comprehension, etc., than those in the Placebo group, who took a pill that looked identical but did not contain these nutrients.

Moreover, these were not individuals with just “mild” cognitive impairment. These graphs show the results, in terms of performance or ability, for those in our study who had MD diagnosed Alzheimer’s. And of course what they show is that within 3 months this nutritional supplement made a significant difference in memory and other abilities for most (approximately 80%) of those who took it.

This next graph shows the composite progress over time, as measured by the dementia rating scale. This is for all of those in our study, including both individuals with mild cognitive impairment, not yet diagnosed with dementia, as well as those with dementia or Alzheimer’s. These were the results over a nine month period.

Screenshot_79

Figure 2

While most participants in both groups showed some improvement at 3 months—likely due to greater familiarity and reduced test anxiety—there was a major difference in the magnitude of effect. As noted above, nearly 80% of those initially on the nutritional formulation showed improvements compared to 53% in the placebo group, and their improvements were significantly greater both in mood and memory, with no significant adverse side effects.

After 3 months the institutional review board monitoring this study, decided we had made our point, reinforcing earlier studies that this formulation can make a significant difference, and therefore they felt it only ethical to allow those who had been in the control group to take it as well. That is what “open label” means. So after that everyone was taking NF (now sold as Perceptiv™) and everyone knew what they were getting – i.e. the label matched the contents.

Lessons Learned

There were many lessons learned from this study, however, there are three in particular that seem most relevant for our purposes that I would like to review with you. First…

A Pill Alone May Not Be Enough

If you look carefully at the graphs above you will see the single lines extending below the black blocks. These represent those individuals who did not fare so well. These are the 20% or so who did not make significant progress overall, and were more likely to continued their decline.

Some of these improved after 3 months, others may have had strong genetic factors influencing their decline, such as the Apoe-4 “Alzheimer’s” gene. We know that genetics and family history do play a significant role in many if not most cases of Alzheimer’s. However, others in our study with a documented family history and likely genetic predisposition for Alzheimer’s made great progress! In fact Dr. Shea has shown in other animal studies that the NF formulation can, to a significant degree, help to compensate for the ApoE-e4 gene.

Otherwise, it would be helpful to know why some did better on this formula than others, i.e what other factors made a difference here. Generally we did not track other lifestyle variables in this study, like diet, exercise etc., but Dr. Morrow and I did note a few of these from our conversations with family members.

One of the first things we observed, was that those who did not eat a nutritious diet, who did not eat a variety of vegetables, for example, did not progress as well as those who did. On the other hand those who consumed significant quantities of sugar, ice-cream, or other sweet treats, pastries or other high carb “junk food,” did not progress as well as those who did not.

Second, although these were not carefully measured, a few other apparent lifestyle deterrents to progress included, lack of physical or mental activity, lack of water intake, often associated with a urinary tract infection, and a lack of sleep or stress.

Third, it was also interesting that a high percentage of those in our study were on a statin (cholesterol) or antacid medication. Dr. Shea also observed in previous studies that those who did not do so well were generally older and took more medications than those who made better progress. Of course it’s hard to say how much those contributed. Was it the medication or the disorder the medication was taken for. Actually Dr. Perlmutter suggests it could be both. But these seem worth considering, and we have written about those in other publications.

The point I want to make here is that researchers are now coming to realize that the only way to ensure a healthy brain and avoid the brain damaging plagues of our age is to develop a individualized or         personalized brain-healthy diet and lifestyle, like Dr. Bredesen has doneAnd as we get older a good targeted higher potency nutritional supplement or two may be needed as well. That seems to be the only approach that can create a synergistic effect powerful enough to provide all that our body and brain need to succeed as we advance in years.

The Sooner the Better

Previous studies have shown that the Alzheimer’s disease process is generally on a very long continuum, that usually begins 20-40 years or more before significant symptoms arise or decline becomes apparent. And the earlier we address these deviant processes the easier they will be to overcome. Therefore, as might be expected, the positive results in this study were more pronounced for those in the early to mid stages of Alzheimer’s rather than the later stages.

This also supports the findings of the above noted “international review” as well as other studies which suggest Alzheimer’s is associated with greater nutritional deficits as we age. And that nutrients may be harder to assimilate as we age, which emphasizes the importance of early nutritional interventions to arrest or reverse symptom decline. Because the further down that road we allow ourselves to go, the harder or less likely it is that we will be able to regain full mental health and abilities.

More than Symptom Relief

One of the limitations of this particular study was that, although we were able to show symptom reversal in individuals diagnosed with Alzheimer’s disease, our measures were not sufficient or appropriate to show disease remission. So we can not claim that this arrested or mitigated AD per se.

However, towards the end of this report Dr. Shea notes that while the “clinical analyses were confined to symptomatic efficacy… preclinical studies demonstrate that components of [this formulation] support general nervous system health (e.g., reduced oxidative damage and homocysteine levels, increased glutathione levels and bioavailability, increased acetylcholine levels) and aspects of neuronal health directly related to dementia (reduction of PS-1 expression, secretase activity, intracellular and extracellular Abeta deposits).”[9]

He further notes “general beneficial effects of NF in preclinical studies may have alleviated AD-related neuropathology. For example, oxidative stress is an early event in AD neuropathology, homocysteine augments amyloid induced oxidative damage and is correlated with impaired executive function, reduced levels of glutathione potentiates neuronal oxidative damage, and reduced acetylcholine levels correlate with impaired cognitive performance.”

Thus, he concludes, this formulation “may harbor disease-modifying properties if administered early enough* as part of a preventative approach,” i.e. in conjunction with “a healthy diet, and lifestyle, involving adequate physical activity, social interactions and cognitive stimulation.”[10]

* at the onset of, or prior to, cognitive decline to maximize efficacy

Further Evidence Prevention is Possible

In addition to this study at least 6 other major studies (including the FINGER & UCLA studies noted above) have now shown symptom reduction in at risk seniors, even some at “high” risk. Instead of continuing their decline, they were able to improve their cognitive abilities– i.e. move in the opposite direction. All of which suggests that indeed prevention is possible, especially when these steps are taken before symptoms get too bad.

For another review of the facts on this topic see my article Can Alzheimer’s Disease be Prevented or Arrested on the Website of the American Academy of Anti-Aging Medicine.
http://www.antiagingage.com/anti-aging-research-articles/item/can-alzheimers-disease-be-prevented-or-arrested

New Hope Rising – Summary

Despite discouraging claims to the contrary, many researchers and practitioners have long declared that dementia prevention is possible, but until recently there had not been many studies robust enough to prove it. Nor did we know the full composition of the lifestyle that would be best for the brain. But now thanks to this recent research we do know a great deal about those details. And we see from the studies reviewed here that indeed prevention is possible! Hopefully, you will soon see this healthy lifestyle approach become the standard of practice in the US as well as Europe. In fact you may even be able to help with that.

We believe that by adopting a brain healthy lifestyle with some additional supplementation, and mental stimulation a large percentage of our population living today will be spared the ravages of cognitive decline, and the plague of Alzheimer’s may be reduced to a footnote in medical history books. But the evidence is clear, the earlier we start this the greater our chances of arresting and reversing this destructive process.
On a personal level, if you and your loved ones will adopt the brain healthy lifestyle advocated by the American Brain Council and it’s professionals certified in Brain Health and Dementia Prevention Education, and stick with it, this research suggests you will enjoy a longer, healthier, and happier life!

David R. Larsen, MFHD, CDPT
You can email me if you have questions regarding this article, or if you are a hearing or speech professional interested in becoming certified in this field contact me at David@ABCbrain.org

References

[1]  Ngandu T, Lehtisalo J, Solomon A, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER):a randomised controlled trial. Lancet: Published Online March 12, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60461-5 http://www.ncbi.nlm.nih.gov/pubmed/25771249

[2] Ibid

[3] Lee K.S., Lee Y., Back J.H., Son S.J., Choi S.H., Chung Y.-K., Lim K.-Y., Noh J.S., Koh S.H., Oh B.H., Hong C.H. “Effects of a Multidomain Lifestyle Modification on Cognitive Function in Older Adults: An Eighteen-Month Community-Based Cluster Randomized Controlled Trial.” Psychother Psychosom 2014;83:270-278. http://www.worldhealth.net/news/anti-aging-pro-cognition/

[4]  Bredesen DE, (2014) Reversal of cognitive decline: A novel therapeutic program. Aging, Sept 2014, Vol 6, 9  http://www.impactaging.com/papers/v6/n9/full/100690.html

[5] Ibid

[6] Lopes da Silva S, Yaffe K, Sijben J. et al (2014) Plasma nutrient status of patients with Alzheimer’s disease: Systematic review and meta-analysis. Alzheimer’s & Dementia, 10 485–502. http://www.ncbi.nlm.nih.gov/pubmed/24144963

[7]  Remington et al., 2015, Journal of Alzheimer’s disease doi: 10.3233/JAD-142499

[8]  Email DavidRJL@aol.com for a copy of this study including Dr. Shea’s summary of research on Perceptiv’s epigenetic influence, also for more information about this formulation and where you can obtain it.

[9]  ibid

[10] ibid

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