How to prevent Alzheimer’s disease. How to cure Alzheimer’s disease. These are certainly topics of growing interest in the world today. It’s been almost seven years since I devoted a newsletter to Alzheimer’s disease (AD). During that time, researchers have learned a great deal–most of which confirms what I proposed back then. But enough has changed that it’s worth revisiting the topic. And two new reports on Alzheimer’s disease make the timing particularly apropos.
Before we talk about how to prevent Alzheimer’s disease, we need to talk about what it is.
According to the National Institute of Aging, Alzheimer’s disease is defined as an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear after age 60. Estimates vary, but experts suggest that as many as 5.1 million Americans may have Alzheimer’s disease. It is the most common cause of dementia among older people. Dementia itself is defined as the loss of cognitive functioning–thinking, remembering, and reasoning–and behavioral abilities, to such an extent that it interferes with a person’s daily life and activities. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for the basic activities of daily living.
The identifying pathological characteristics of Alzheimer’s brains include:
- Abnormal levels of beta-amyloid protein that form amyloid plaques.
- Tau proteins clump together inside neurons and form neurofibrillary tangles.
- Neurons are lost.
- And glial cells — which normally support, protect, or nourish nerve cells — are over-activated in Alzheimer’s.
The big question, though, is what is the trigger? If we want to learn how to prevent Alzheimer’s disease, we need to know what initiates it in the first place. Which of these four characteristics, if any, is the cause of Alzheimer’s and which are merely associated effects?
The Cost of Alzheimer’s Disease and Dementia
A study by the RAND Corporation just published in the New England Journal of Medicine estimates that the cumulative costs of caring for people with dementia currently ranges from $157 billion to as much as $215 billion annually in the United States.1 Michael D. Hurd, Paco Martorell, Adeline Delavande, et al. “Monetary Costs of Dementia in the United States.” The New England Journal of Medicine, v. 368, no. 14, Apr. 2013, p. 1326-1334. http://www.nejm.org/doi/full/10.1056/NEJMsa1204629#t=articleResults If correct, this would mean that already the costs for dealing with dementia exceed the costs for heart disease and cancer combined. Even worse, the study projects that by 2040, these costs will nearly double.
“The economic burden of caring for people in the United States with dementia is large and growing larger,” said Michael Hurd, the study’s lead author and a senior economist at RAND, a nonprofit research organization. “Our findings underscore the urgency of recent federal efforts to develop a coordinated plan to address the growing impact of dementia on American society.”
The RAND study is based on findings from the Health and Retirement Study, an ongoing survey of individuals in the United States aged 51 and older that began in 1992, and is supported by the National Institute on Aging and the Social Security Administration. A subset of that study group received a detailed in-home clinical assessment for dementia as part of the Aging, Demographics, and Memory Study, a nationally representative examination of dementia in the United States.
The survey included an assessment of whether people could perform daily activities such as dressing themselves and preparing their own meals. Participants also were asked about their out-of-pocket health care expenses for services such as nursing home stays, home health care, and other medical services. Other questions asked whether they received help from others for their daily living activities. Medicare spending information was linked to medical claims for most participants.
The study estimated that 14.7 percent of Americans aged 71 or older suffered from dementia in 2010, a number somewhat lower than what has been found in other, smaller studies.
The total economic cost of dementia in 2010 was estimated to be $109 billion for care purchased, or $159 billion to $215 billion when the monetary value of informal care was included. The range of estimates reflects two different methods the researchers used to place a value on unpaid care. The per-person cost of dementia was $56,290 or $41,689 depending on methodology. Medicare paid about $11 billion of the dementia-related costs.
Researchers say that the main component of the dementia costs is for institutional and home-based long-term care rather than medical services. The costs associated with nursing home care and formal and informal home care comprise 75 percent to 84 percent of dementia costs.
“There are no signs that the costs of dementia will decrease given that the nation will have a larger number of 85-year-olds in the future than we do today,” Hurd said. “Unless there is some sort of medical breakthrough, these costs will continue to rise.”
What this fundamentally means is that Alzheimer’s is about the next generation–those now in their teens, twenties, and thirties. They’ll be the ones who have to pick up the tab for these astounding costs. They’ll have to pay for us–the current and in-the-pipeline older Americans.
You need to understand how big this burden actually is. At $56,290 per year per dementia patient — and with Americans having a 1-in-8 chance of getting dementia after the age of 65 (and a 1 in 2.5 chance after the age of 85) — the fiscal balance sheets of the future will be consumed by Alzheimer’s care giving costs. By 2040, we are talking about a half trillion dollars a year…just for care giving costs for dementia in the US alone. Extrapolate that out through the rest of the world, and the financial and societal impact is almost unimaginable.
President Obama recently inserted $100 million into his 2013 budget proposal that he just sent to Congress to fund the BRAIN Initiative to support technologies to map the brain.
Unfortunately, although the initiative itself had bipartisan support, the budget and anything in it that didn’t cut spending did not. At the moment, approval of funding for the initiative probably stands at about 60/40. If not approved, it might end up as a classic example of cutting off your nose to spite your face. Considering that we’re looking at a half trillion a year in costs by 2040 unless something changes, a one-time investment of $100 million to help cut that seems rather trivial. Embarrassingly, over in Europe, which is currently facing even tougher financial circumstances than the US, the Dutch government has announced that it will be investing approximately $260 million in research and care improvements (half provided by the Dutch Government and half from private sources) because it believes it will save them billions in future costs.2 “Millions earmarked for dementia as experts warn of looming disaster.” 4 April 2013. DutchNews.nl (Accessed 11 April 2013.) http://www.dutchnews.nl/news/archives/2013/04/despite_cuts_in_healthcare_spe.php It would be nice to think that the US could at least match the Dutch investment–considering that the US GDP is 18 times that of the Dutch.
Genes linked to higher risk of Alzheimer’s
As mentioned earlier, a couple of new studies on Alzheimer’s have just been published. Let’s take a look at those and see how they might impact future developments.
Statistically, Alzheimer’s disease is “slightly” more common among African Americans than among white Americans living in the same community, but no genetic reasons have ever been identified for this statistical anomaly…until now.
In the largest study ever looking for genetic risk factors for Alzheimer’s in the African American population, researchers reported in the Journal of the American Medical Association that they had identified two genes that seem to be responsible.3 Reitz C, Jun G, Naj A, et al. “Variants in the atp-binding cassette transporter (abca7), apolipoprotein e ε4,and the risk of late-onset Alzheimer disease in African Americans. 2013/04/10 JAMA. 2013;309(14):1483-1492. http://jama.jamanetwork.com/data/Journals/JAMA/926784/joc130032_1483_1492.pdf The press, as might be expected, made a big deal out of this, but there is less here than meets the eye.
Curiously, these same two genes are also associated with a higher risk of the neurodegenerative disorder among whites. But for reasons, as yet unknown, changes in these genes confer a higher risk of disease among African Americans than among whites. The study involved nearly 6,000 African American participants aged 60 or older, about 2000 of whom had Alzheimer’s. The researchers found that variants in the genes ABCA7 and ApoE increased the risk of developing Alzheimer’s by 80% and more than 100%, respectively. By comparison, ABCA7 is likely responsible for a 10% to 20% increased risk for Alzheimer’s within white populations (again, living in the same communities), and about 40% of whites with certain forms of ApoE are diagnosed with Alzheimer’s.
At first glance, these might look like significant differences between African Americans and whites in terms of Alzheimer’s, but medically speaking they are not. In fact, they are considered modest increases at most. From a medical point of view, a gene would need to increase the chances of getting a disease by well over 200 percent before it was identified as carrying a significant risk. And even more to the point, ABCA7 is not very common. About 9 of every 100 African-Americans with Alzheimer’s have the gene, compared with 6 out of 100 who did not have the disease. Statistically speaking, it means that when it comes to Alzheimer’s, this gene impacts only about 3 out of 100 more African Americans than whites. In other words, not very significant in the grand scheme of things. When looking for the cause of Alzheimer’s, we need to look elsewhere.
Nevertheless, the research points to the fact that genetics likely plays at least some role in Alzheimer’s, although at the moment, that role looks small. ABCA7’s role in the Alzheimer’s doesn’t come as a complete surprise; it is involved in producing cholesterol and lipids, and some research suggests that Alzheimer’s disease may involve aberrations in fat metabolism that are similar to those behind heart disease. More significantly, though, ABCA7 also regulates the transport of proteins, including those responsible for the production of amyloid plaque. And right now, the most likely culprit in the onset of Alzheimer’s is the build-up of sticky beta amyloid plaques in the brain.
Also released last week, were the results of a study published in the Journal of Neuroscience. Using a new genetically engineered lab rat that has the full array of brain changes associated with Alzheimer’s disease, the results of the study support the hypothesis that an increase in a beta-amyloid (Aß) plaque in the brain is the likely trigger of Alzheimer’s disease.4 Robert M. Cohen, Kavon Rezai-Zadeh, Terrence Town, et al. “A Transgenic Alzheimer Rat with Plaques, Tau Pathology, Behavioral Impairment, Oligomeric Aß, and Frank Neuronal Loss.” The Journal of Neuroscience, 10 April 2013, 33(15): 6245-6256. http://www.jneurosci.org/content/33/15/6245.abstract
Plaque-forming beta-amyloid molecules are derived from a larger protein called amyloid precursor protein (APP). One hypothesis as to the cause of Alzheimer’s states that increases in beta-amyloid initiate brain degeneration. Genetic studies on familial forms of Alzheimer’s support the hypothesis by linking the disease to mutations in APP, and to presenilin 1, a protein thought to be involved in the production of beta-amyloid.
The researchers performed a variety of experiments confirming the presence of neurofibrillary tangles in brain regions most affected by Alzheimer’s (such as the hippocampus and the cingulate cortex), and those regions also happen to be involved in learning and memory. In the study, the rats lost up to about 30 to 35 percent of their neurons in the aforementioned brain regions. Not surprisingly, the rats also began to lose their ability to do mental tasks, like navigate a maze. And as the animals got older, they performed even worse, much as you would see in a human patient that would have these same mutations.
“Our results suggest that beta-amyloid can drive Alzheimer’s in a clear and progressive way,” said Dr. Terrence Town, the study’s senior author.
How to Prevent Alzheimer’s Disease
While we’re all waiting for the US Congress to pass funding to initiate the decades long research on the brain to find a cure for Alzheimer’s or for the pharmaceutical industry to come up with a side effect riddled miracle cure before then, is there anything we personally can do about Alzheimer’s–anything we personally can do to lower our chances of getting it, regardless of any genetic predisposition? The simple answer is that at this time there is no “proven” way to prevent Alzheimer’s disease. Fortunately, that simple answer is not necessarily the complete answer. If we look outside the medical community, we find that there are some things we can do, that although not proven, are nevertheless “a good bet.”
Assuming that the current leanings of the scientific community are correct, that beta amyloid is the key to Alzheimer’s–something that more and more studies keep pointing to–then the key to preventing AD lies in inhibiting the production of Aß plaque in the brain. And as it turns out, carnosine, a naturally occurring dipeptide that I first pointed to almost 20 years ago as likely inhibiting the formation of beta amyloid plaque in the brain, has received confirming support in that regard in multiple studies over the years.
First Carnosine Study
A 2007 study published in the Journal of Alzheimer’s Disease found that carnosine works to help Alzheimer’s patients through multiple pathways–although suppression of Aß toxicity is primary.5 Hipkiss AR. “Could carnosine or related structures suppress Alzheimer’s disease?” J Alzheimers Dis. 2007 May;11(2):229-40. http://www.ncbi.nlm.nih.gov/pubmed/17522447
First Carnosine Alzheimer’s Disease Pathway
I’m including a little extra detail in this first pathway as an example of how complex bio-chemical reactions in the human body are–and why it’s so difficult for researchers to identify them all.
- Glycated protein accumulates in the cerebrospinal fluid (CSF) of Alzheimer’s’ patients.
- Homocarnosine levels in human CSF dramatically decline with age.
- CSF composition and turnover is controlled by the choroid plexus which possesses a specific transporter for carnosine and homocarnosine.
- Carnosine reacts with protein carbonyls and suppresses the reactivity of glycated proteins.
- Carbonic anhydrase (CA) activity is diminished in AD patient brains. Administration of CA activators improves learning in animals.
- Carnosine is a CA activator.
Other Carnosine Alzheimer’s Disease Pathways
- Carnosine inhibits production of oxygen free-radicals, scavenges hydroxyl radicals and reactive aldehydes, and suppresses protein glycation.
- And, of course, as already discussed, carnosine suppresses amyloid-beta peptide toxicity.
In summary, according to the study, “These observations suggest that carnosine and related structures should be explored for therapeutic potential towards AD and other neurodegenerative disorders.”
Second Carnosine Study
A 2011 study restated the connection between Alzheimer’s and beta amyloid plaque but also reinforced the ultimate complexity of the pathways that lead to the disease–and again referred to the value of using carnosine supplementation to prevent and treat the disease throughout its multiple pathways of benefits.6 Carlo Corona,Valerio Frazzini,Elena Silvestri,et al. “Effects of Dietary Supplementation of Carnosine on Mitochondrial Dysfunction, Amyloid Pathology, and Cognitive Deficits in 3xTg-AD Mice.” PLoS One. 2011; 6(3): e17971. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058055 As the study said, the pathogenic road map leading to Alzheimer’s disease is still not completely understood. However, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of Aß and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the imbalance of metals that naturally occur in the body like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, carnosine supplementation may be beneficial in the prevention and treatment of AD not only because it promotes a strong reduction in the hippocampal intraneuronal accumulation of Aß but also because its free-radical scavenging and metal chelating properties completely rescues AD and aging-related mitochondrial dysfunctions. Using L-carnosine supplementation, “We only observed a trend toward the amelioration of cognitive deficits.”
Third Carnosine Study
And finally, as we have mentioned multiple times, the aggregation of beta amyloid into fibrillar structures is a hallmark of Alzheimer’s disease. Thus, preventing the self-assembly of the Aβ peptide into such structures is an attractive therapeutic strategy. Well, a study published just last month in ChemBioChem indicates yet again that carnosine can do just that.7 Attanasio F, Convertino M, Magno A, Caflisch A, et al. “Carnosine Inhibits Aß42 Aggregation by Perturbing the H-Bond Network in and around the Central Hydrophobic Cluster.” Chembiochem. 2013 Mar 18;14(5):583-92. http://www.ncbi.nlm.nih.gov/pubmed/23440928 Using both experimental techniques and atomistic simulations to investigate the influence of carnosine, the researchers found that carnosine seems to block the pathway toward toxic aggregates by upsetting the hydrogen bond network involved in fibrillogenesis–yet another pathway to Alzheimer’s disease.
The bottom line is that although not yet “proven” to prevent or treat Alzheimer’s disease, carnosine definitely looks like a good bet based on its ability to inhibit multiple pathways to the development of Alzheimer’s, but most especially based on its ability to prevent the formation of beta amyloid plaques in the brain.
Acetyl-l-carnitine and Alzheimer’s Disease
When I first developed a formula based on L-carnosine over a decade ago, I also included acetyl-l-carnitine (ALC), an amino acid that is naturally produced in the body. At the time, the purpose was not to address AD, but to complement the action of carnosine — particularly because of ALC’s ability to clean up lipofuscin, a waste product resulting from carnosine’s anti-glycation activity. But ALC also offered another benefit since it could so readily cross the blood-brain barrier and work to protect brain cells. Given that ability, it shouldn’t be much of a surprise that subsequent research would find that ALC might be beneficial in treating Alzheimer’s. And in fact, a 2011 study found that ALC might be able to do just that by virtue of its ability to reduce high levels of homocysteine in the brain. Specifically, the study suggested that high levels of homocysteine in the brain might play a role both in inducing tau protein to form into the filament tangles in the brain as well as Aβ accumulation–both of which are associated with the onset and progression of AD.8 Zhou P, Chen Z, Zhao N, Liu D, et al. “Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities.” Rejuvenation Res. 2011 Dec;14(6):669-79. doi: 10.1089/rej.2011.1195. http://www.ncbi.nlm.nih.gov/pubmed/21978079
The researchers found that supplementation with ALC inhibited the formation of tau tangles and the accumulation of beta amyloid plaque in the brain, which “remarkably” improved the memory deficits associated with AD. To quote from the study, “Supplement of ALC almost abolished the homocysteine-induced tau hyperphosphorylation at multiple AD-related sites. Supplementation of ALC also suppressed the phosphorylation of ß-amyloid precursor proteins (APP), which may underlie the reduction of Aß.”
This makes regular supplementation with a formula based on L-carnosine and Acetyl-l-carnitine a really good bet at this point in our understanding of Alzheimer’s disease.
Note: recently, a study appeared in the news that implicated carnitine consumption and supplementation with heart disease. Don’t worry about it. There’s less here than meets the eye. Carnitine and Acetyl-l-carnitine are not the same thing, and the study is far from conclusive. In fact, four days after that study came out, a different study concluded that carnitine actually protects against heart disease. Go figure!
If you’re still thinking that supplementation with carnosine and ALC might not be the way to go and that you’d rather wait for the results of the President’s BRAIN initiative, you might want to rethink that. Of the paltry $100 million being proposed for the study–assuming that Congress ever approves it–only $28 million is actually being devoted to anything connected to Alzheimer’s.9 Office of the Press Secretary. “Fact Sheet: BRAIN Initiative” 2 April 2013. The White House. (Accessed 14 April 2013.) http://www.whitehouse.gov/the-press-office/2013/04/02/fact-sheet-brain-initiative Specifically, that $28 million is to map out the brain’s neural networks and unravel how they interrelate in order to “truly understand how the brain operates in both healthy and diseased states.” In fact, there is no intention to even find a cure or treatment for Alzheimer’s in the BRAIN initiative — merely to lay “the groundwork for prevention and treatment of age-related neurological diseases.”
The bottom line is, that for now and the foreseeable future, you are on your own. If you’re looking to prevent Alzheimer’s disease, that means that the primary option available is to supplement daily with a formula that contains L-carnosine and Acetyl-l-carnitine. And it doesn’t hurt that this same formula is also likely to keep you looking younger and feeling younger in the process. Also, if you haven’t already done so, check out our previous report on Alzheimer’s for other steps you can take in support of L-carnosine and Acetyl-l-carnitine.
|↑1||Michael D. Hurd, Paco Martorell, Adeline Delavande, et al. “Monetary Costs of Dementia in the United States.” The New England Journal of Medicine, v. 368, no. 14, Apr. 2013, p. 1326-1334. http://www.nejm.org/doi/full/10.1056/NEJMsa1204629#t=articleResults|
|↑2||“Millions earmarked for dementia as experts warn of looming disaster.” 4 April 2013. DutchNews.nl (Accessed 11 April 2013.) http://www.dutchnews.nl/news/archives/2013/04/despite_cuts_in_healthcare_spe.php|
|↑3||Reitz C, Jun G, Naj A, et al. “Variants in the atp-binding cassette transporter (abca7), apolipoprotein e ε4,and the risk of late-onset Alzheimer disease in African Americans. 2013/04/10 JAMA. 2013;309(14):1483-1492. http://jama.jamanetwork.com/data/Journals/JAMA/926784/joc130032_1483_1492.pdf|
|↑4||Robert M. Cohen, Kavon Rezai-Zadeh, Terrence Town, et al. “A Transgenic Alzheimer Rat with Plaques, Tau Pathology, Behavioral Impairment, Oligomeric Aß, and Frank Neuronal Loss.” The Journal of Neuroscience, 10 April 2013, 33(15): 6245-6256. http://www.jneurosci.org/content/33/15/6245.abstract|
|↑5||Hipkiss AR. “Could carnosine or related structures suppress Alzheimer’s disease?” J Alzheimers Dis. 2007 May;11(2):229-40. http://www.ncbi.nlm.nih.gov/pubmed/17522447|
|↑6||Carlo Corona,Valerio Frazzini,Elena Silvestri,et al. “Effects of Dietary Supplementation of Carnosine on Mitochondrial Dysfunction, Amyloid Pathology, and Cognitive Deficits in 3xTg-AD Mice.” PLoS One. 2011; 6(3): e17971. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058055|
|↑7||Attanasio F, Convertino M, Magno A, Caflisch A, et al. “Carnosine Inhibits Aß42 Aggregation by Perturbing the H-Bond Network in and around the Central Hydrophobic Cluster.” Chembiochem. 2013 Mar 18;14(5):583-92. http://www.ncbi.nlm.nih.gov/pubmed/23440928|
|↑8||Zhou P, Chen Z, Zhao N, Liu D, et al. “Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities.” Rejuvenation Res. 2011 Dec;14(6):669-79. doi: 10.1089/rej.2011.1195. http://www.ncbi.nlm.nih.gov/pubmed/21978079|
|↑9||Office of the Press Secretary. “Fact Sheet: BRAIN Initiative” 2 April 2013. The White House. (Accessed 14 April 2013.) http://www.whitehouse.gov/the-press-office/2013/04/02/fact-sheet-brain-initiative|