Galantamine reduces dementia mortality while …

Alzheimer’s Deaths
Rival Cancer’s

The brain, the masterpiece of creation, is becoming
better known with increased research

By Will Block

“The brain, the masterpiece of creation, is almost unknown to us.”
— Nicolaus Steno, (1638–1686)

“Where have ye been? behind
What curtain were ye from me hid so long?”

— Thomas Treherne, (1637–1674)


Alzheimer’s shortens
the timeline of “Forever”
D id you know that Ronald Reagan’s death certificate indicated that he died from pneumonia? How could this be the case when he was all but a poster model for Alzheimer’s disease? The cause of death was a shortsighted mistake, sort of like saying that the cause of death from an accident was bleeding. Without the accident there would have been no bleeding; without Alzheimer’s, pneumonia would not have occurred. Pneumonia is a frequent complication of AD.

Dementia-Less Death Certificates All Too Common

Undoubtedly the biggest problem with death certificates is that many list the immediate cause of death, rather than the real cause, without which death would not have happened. Also, most death certificates are signed by physicians who are unfamiliar with the medical histories of the dead. Attributing Alzheimer deaths to other diseases is all too common. President Reagan got pneumonia because he had Alzheimer’s and he could not fight it. Alzheimer’s takes away everything, such as the ability of the body to defend itself, leaving it open to infections. Alzheimer’s even affects the ability to breathe. Other frequent complications are urinary-tract infections and organ failure.

Taking up the issue of these inaccuracies, a very recent study published in Neurology pivoted from the well-documented literature that AD and other forms of dementia are underreported on death certificates.1

Dementia—along with Alzheimer’s, its worst form—contributes to death insidiously through a cascade of events over the course of time. Eventually, severe dementia-caused complications such as swallowing disorders and malnutrition can lead to fatal conditions such as pneumonia. But these complications are really the result of Alzheimer’s and not the cause of death.

Alzheimer’s Approaches Cancer and Heart Disease Tolls

It is simply amazing that we are just now finding that Alzheimer’s disease may contribute to nearly as many deaths as are attributed to the leading killers, heart disease and cancer. Yet, according to the new study, when the researchers calculated the total number of deaths from dementia in a cohort group followed for 8 years, and applied these findings to data for 2010, the number was much higher than reported.

Lead study author Bryan James of the Rush University Medical Center in Chicago, said that his team’s findings show that deaths from Alzheimer’s far exceed what is reported by the Centers for Disease Control, which derives its figures (83,000 for the last complete year calculated) from what is listed on death certificates.

In the study, more than 2,500 people, aged 65 and older (the mean age was ~73 years), were tested annually for Alzheimer’s over the length of the study (8 years on average). At the end, 1,090 study participants had died, and among these were 559 participants who did not have dementia when the study began. Altogether, Alzheimer’s was confirmed in 90 per cent of patients who had been clinically diagnosed. The confirmation was by autopsy.

The researchers found that the death rate among study participants was four times higher after an Alzheimer’s diagnosis in subjects aged 75 to 84, and nearly three times higher in participants aged 85 and older. More than one-third of all deaths in those age groups were attributable to Alzheimer’s disease.

Six Times the Number of Deaths

According to James, those figures would translate into about 503,400 deaths from Alzheimer’s among U.S. adults aged 75 and over in 2010. That’s nearly six times higher than the more than 83,000 reported Alzheimer’s deaths. James said it is clear from the findings that Alzheimer’s disease and other forms of dementia are underreported on death certificates and in medical records.

Another reason for the under­reporting is that a diagnosis of Alzheimer’s greatly increases the cost of custodial care for the elderly. And surprise, they’re ineligible for “assisted living” type arrangements. These measures often require restraint or 24/7 lockup so they don't wander off. Given the astronomical cost, Medicare doesn’t cover it.

James also noted that attempts to identify a single cause of death fail to capture the true process of dying among the elderly, who often suffer from multiple health problems.

“Determining the true effects of dementia in this country is important for raising public awareness and identifying research priorities regarding this epidemic,” James said.2 The Wall Street Journal in a recent editorial3 also called for a national effort to address what may now be viewed as a countrywide crisis. Fat chance, given the “success” of the War on Cancer.

Can Alzheimer’s Mortality Be Forestalled?

Published less than two weeks before the James et al paper, a significant study found great favor for galantamine’s ability to sustain life in Alzheimer’s victims.4 Galantamine is a dual-action herb that decreased the breakdown of the important memory molecule acetylcholine, thus empowering its brain boosting abilities while enhancing nicotinic cholinergic activity, thereby increasing sensitivity to acetylcholine.

Designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD, the study showed that galantamine not only slows memory loss, but decreases death from all causes in Alzheimer’s patients. This study has been previously reported in Life Enhancement, based on a poster session from a conference and the blog of the lead author, Professor Klaus Hager. (see “Galantamine Cuts Mortality” and “Galantamine Slashes Heart Attacks and Death” in the April and August 2013 issues, respectively). But at last, the complete paper has been published!

All of the subjects of the study were diagnosed with Alzheimer’s disease, with 1,024 taking galantamine and 1,021 taking placebo. The mean age of the subjects was ∼73 years, and the mean baseline for the baseline mini–mental state examination (MMSE) was a score of 19, the threshold between mild and moderate Alzheimer’s.

Do You Want to Know if You’ll Get Alzheimer’s?

Scientists recently discovered and validated a set of ten lipids from peripheral blood that predicted conversion to either amnesic mild cognitive impairment or Alzheimer’s disease within a 2–3 year timeframe with over 90% accuracy.1 This biomarker panel may be sensitive to early neurodegeneration of preclinical Alzheimer’s disease, by perhaps as much as decades earlier.

According to lead researcher Mark Mapstone at the University of Rochester Medical Center in New York, “We think the decrease in these chemicals reflects the breakdown of neural populations in the brain.”2 Mapstone also said, “In my experience, the majority of people are very interested to know whether they will get Alzheimer’s. They believe that knowledge is power—particularly when it comes to your own health. We may not have any therapy yet, but there are things we can do—we can get our financial and legal affairs in order, plan for future care, and inform family members.”

While several blood tests can diagnose Alzheimer’s, until now, none has had the sensitivity to predict its onset, such as the current test.

The implications of this research are huge: Though there is currently no known cure for Alzheimer’s, being able to predict its onset could mean patients are treated before they get any symptoms—which could, one day, possibly even prevent the onset of the disease.

Although Dr. Mapstone’s advice to get one’s affairs in order may be reasonable—in terms of the view of orthodox medicine—we believe that steps can be taken in addition to maintaining one’s affairs that offer a more positive outlook if one is faced with a biomarker pattern that predicts the likelihood of impending Alzheimer’s. We believe that removing heavy metals and maintaining optimum blood flow to the brain with IV or oral chelation therapy, enhancing blood flow and glucose uptake in the brain with Vinpocetine, optimizing brain cell membranes with Phosphatidylserine and Acetyl-L-Carnitine, removing cell-clogging lipofuscin with DMAE, and increasing neurotransmitters such as acetylcholine and it’s activity with Galantamine, along with the use of lithium, hesperidin, turmeric, and omega-3 fish oil will combine to delay, and in many cases reverse the damaging effects of Alzheimer’s.

References

  1. Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, Macarthur LH, Hall WJ, Fisher SG, Peterson DR, Haley JM, Nazar MD, Rich SA, Berlau DJ, Peltz CB, Tan MT, Kawas CH, Federoff HJ. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014 Mar 9. doi: 10.1038/nm.3466.
  2. Thomson H. First test to predict Alzheimer’s years in advance. New Scientist. March , 2014. www.newscientist.com/article/dn25190-first-test-to-predict-alzheimers-years-in-advance.html#.Uy-KVSQh1GE. Accessed: March 23, 2014.

Mortality Rate Significantly Lower in Galantamine Group

Only 32% of patients (661/2,045) completed the study, while 27% (554/2,045) withdrew. The remaining 41% (830/2,045) did not complete the study due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo.

The hazard ratio equaled 0.58 with a high probability of accuracy. In survival analysis, the hazard ratio is the ratio of the hazard rates corresponding to the conditions described by two levels of an explanatory variable. For example, in a drug study, the treated population may die at twice the rate per unit time as the control population. The hazard ratio would be 2. Conversely, if the hazard ratio is 0.58, as in the considered study, the likelihood of death was ­lessened by 42% in the galantamine group.

Also, cognitive impairment significantly worsened in the placebo (a −2.14 drop in the MMSE) compared with the galantamine group (only a drop of −1.41 in the MMSE). This meant that many of the subjects retained mild cognitive impairment status while others sank into moderate status.

Furthermore, functional impairment, based on mean change in the Disability Assess¬ment in Dementia (DAD) score, at month 24 significantly worsened in the placebo versus the galantamine group.

From these results we can say that long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients.

Galantamine Combined with a Choline Donor

An Italian adjunctive-treatment study showed that when galantamine is combined with a choline precursor such as choline alphoscerate (CA), the results are better (and perhaps synergistic) than galantamine alone. Nevertheless, this has caused little impact on galantamine treatment studies (see “Alzheimer’s Breakthrough” in the April 2012 issue of this publication).5 Other studies, conducted by members of the Italian researchers’ group have also reported that when CA is combined with the AChEI drug rigvastigmine, cholinergic enhancement is more effective than with each of the single compounds. Most galantamine studies are conducted by drug companies, which are not generally predisposed to sell combination drugs, as they are frowned on by the FDA. Nevertheless, the combination of the acetylcholinesterase inhibitor galantamine and the cholinergic precursor CA produces neuroprotective effects greater than the sum of those observed with single compounds. Thus, there is likely to be a significant boost in the value of galantamine for those concerned about memory loss.

While CA is probably the most effective among choline-containing phospholipids in enhancing in vivo acetylcholine release, it is much more expensive than non-phospholipid acetylcholine releasers, such as choline dihydrogen citrate (CDC). CDC, dollar per gram, is 25 times less expensive than CA (both forms are about 35% choline). CA has also been investigated with positive results on cognitive domain in patients affected by cerebrovascular disorders and vascular dementia. However, choline citrate has never been tested for efficacy in these conditions,, as far as we know. Nevertheless, the association between an ACh breakdown inhibitor (such as galantamine) and a choline precursor (such as CA or CDC) not only increases brain ACh levels more effectively, it may also produce a stronger neuroprotective effect.

References

  1. James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. Contribution of Alzheimer disease to mortality in the United States. Neurology. 2014 Mar 5. [Epub ahead of print]
  2. Rush University Medical Center. Alzheimer’s Disease a Much Larger Cause of Death Than Previously Recognized. March 5, 2014. http://www.rush.edu/rumc/print-page-1298331195426.html. Accessed March 23, 2014.
  3. Vradenburg G, Prusiner S. Alzheimer’s and Its Uncounted Victims. The Wall Street Journal. March 16, 2014. http://online.wsj.com/news/articles/
    SB10001424052702304250204579433552431478652
    Accessed March 23, 2014.
  4. Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, Davis B, Richards HM. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease. Neuropsychiatr Dis Treat. 2014 Feb 21;10:391-401.
  5. Tayebati SK, Di Tullio MA, Tomassoni D, Amenta F. Neuroprotective effect of treatment with galantamine and choline alphoscerate on brain microanatomy in spontaneously hypertensive rats. J Neurol Sci. 2009 Aug 15;283(1-2):187-94.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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