There is substantial evidence that Alzheimer's is related to an increased likelihood of infective agents appearing in the brain. Some researchers believe that infective agents are the principle cause of Alzheimer's. There are a number of bacteria that reside in the human digestive system and can co-exist with our own cells without any harm. However, H. pylori, one that is quite common, has been recently shown to be responsible for stomach ulcers. It has been suspected that H. Pylori might be implicated in Alzheimer's, and, indeed, a recent study showed that Alzheimer's patients had a significantly higher concentration of an antibody against H. Pylori in both their cerebrospinal fluid and their blood than non-Alzheimer's controls [26]. H. pylori was detected in 88% of the Alzheimer's patients but only 47% of the controls. In an effort to treat the Alzheimer's patients, the researchers administered a potent combination of antibiotics, and assessed the degree of mental decline over the next two years [27]. For 85% of the patients, the infection was successfully routed, and for those patients, cognitive improvement was also detected after two years had elapsed. So this was a nice example of the possibility of treating Alzheimer's through antibiotics.
C. pneumoniae is a very common bacterium, estimated to infect 40-70% of adults. But there's a big difference between a bacterium being in the blood stream and making its way into the inner sanctum of the brain. A study of post-mortem samples from various regions of the brains of Alzheimer's patients and non-Alzheimer's controls revealed a remarkably different statistic: 17 out of 19 Alzheimer's brains tested positive for the bacterium, whereas only 1 out of 19 brains from the control group tested positive [5].
Many other infective agents, both viruses and bacteria, have been found to be associated with Alzheimer's, including herpes simplex virus, picornavirus, Borna disease virus, and spirochete [23]. One proposal was that a particular bacteriophage -- a virus that infects the bacterium C. pneumoniae -- might be responsible for Alzheimer's [14]. The authors argued that the phages might make their way into the mitochondria of the host cell and subsequently initiate Alzheimer's.
Thursday, December 17, 2009
11. Ketogenic Diet as Treatment for Alzheimer's
One of the promising new treatment paradigms for Alzheimer's is to have the patient switch to an extremely high fat, low carb diet, a so-called "ketogenic" diet. The name comes from the fact that the metabolism of dietary fats produces "ketone bodies" as a by-product, which are a very useful resource for metabolism in the brain. It is becoming increasingly clear that defective glucose metabolism in the brain (so-called "type-3 diabetes") is an early characteristic of Alzheimer's. Ketone bodies, whether they enter the astrocyte directly or are produced in the astrocyte itself by breaking down fats, can be delivered to adjacent neurons, as shown in the accompanying figure. 
These neurons can utilize the ketone bodies both as an energy source (replacing and therefore relieving glucose) and as a precursor to GABA, a critical neurotransmitter that is widespread in the brain.
Evidence that a ketogenic diet might help Alzheimer's was first found through research conducted on mice who had been bred to be prone to Alzheimer's disease [21]. Researchers found that the mice's cognition improved when they were treated with a high-fat low-carb diet, and also that the amount of amyloid-beta in their brain was reduced. The latter effect would be anticipated based on the premise that amyloid-beta promotes full utilization of glucose anaerobically, as I discussed previously. By having ketone bodies as an additional source of fuel, the dependence on glucose is reduced. But another effect that may be more important than this is the availability of high-quality fats to improve the condition of the myelin sheath.
This idea is supported by other experiments done on human Alzheimer's patients [11] [42]. A placebo-controlled 2004 study [42] of the effect of dietary fat enrichment on Alzheimer's is especially informative, because it uncovered a significant difference in effectiveness for the fat-enrichment for subjects who did not have the apoE-4 allele as compared with those who did. The experimental test group were given a supplemental drink containing emulsified medium chain triglycerides, found in high concentration in coconut oil. The subjects without the apoE-4 allele showed a significant improvement in score on a standard test for Alzheimer's, whereas those with the apoE-4 allele did not. This is a strong indicator that the benefit may have to do with an increase in uptake by the astrocyte of these high-quality fats, something that the subjects with the apoE-4 allele are unable to accomplish due to the defective IDL and LDL transport mechanisms.
These neurons can utilize the ketone bodies both as an energy source (replacing and therefore relieving glucose) and as a precursor to GABA, a critical neurotransmitter that is widespread in the brain. Evidence that a ketogenic diet might help Alzheimer's was first found through research conducted on mice who had been bred to be prone to Alzheimer's disease [21]. Researchers found that the mice's cognition improved when they were treated with a high-fat low-carb diet, and also that the amount of amyloid-beta in their brain was reduced. The latter effect would be anticipated based on the premise that amyloid-beta promotes full utilization of glucose anaerobically, as I discussed previously. By having ketone bodies as an additional source of fuel, the dependence on glucose is reduced. But another effect that may be more important than this is the availability of high-quality fats to improve the condition of the myelin sheath.
This idea is supported by other experiments done on human Alzheimer's patients [11] [42]. A placebo-controlled 2004 study [42] of the effect of dietary fat enrichment on Alzheimer's is especially informative, because it uncovered a significant difference in effectiveness for the fat-enrichment for subjects who did not have the apoE-4 allele as compared with those who did. The experimental test group were given a supplemental drink containing emulsified medium chain triglycerides, found in high concentration in coconut oil. The subjects without the apoE-4 allele showed a significant improvement in score on a standard test for Alzheimer's, whereas those with the apoE-4 allele did not. This is a strong indicator that the benefit may have to do with an increase in uptake by the astrocyte of these high-quality fats, something that the subjects with the apoE-4 allele are unable to accomplish due to the defective IDL and LDL transport mechanisms.
12. NADH Treatment: the Crucial Role of Antioxidants
One of the very few promising treatments for Alzheimer's is the coenzyme, NADH (nicotinamide adenine dinucleotide) [12]. In a placebo-controlled study, Alzheimer's subjects given NADH for six months exhibited significantly better performances on verbal fluency, visual constructional ability and abstract verbal reasoning than the control subjects given a placebo. 
Why would NADH be effective? In the process of converting pyruvate to lactate, lactate dehydrogenase consumes oxygen by oxidizing NADH to NAD+, as illustrated in the accompanying figure. So, if the bioavailability of NADH is increased, it stands to reason that the astrocyte would have an enhanced ability to convert pyruvate to lactate, the critical step in the anaerobic metabolic pathway that is enhanced by amyloid-beta. The process, by absorbing the toxic oxygen, would reduce the damage to the lipids due to oxygen exposure, and would also provide lactate as a source of energy for the neurons.
Why would NADH be effective? In the process of converting pyruvate to lactate, lactate dehydrogenase consumes oxygen by oxidizing NADH to NAD+, as illustrated in the accompanying figure. So, if the bioavailability of NADH is increased, it stands to reason that the astrocyte would have an enhanced ability to convert pyruvate to lactate, the critical step in the anaerobic metabolic pathway that is enhanced by amyloid-beta. The process, by absorbing the toxic oxygen, would reduce the damage to the lipids due to oxygen exposure, and would also provide lactate as a source of energy for the neurons.
13. Excessive Oxygen Exposure and Cognitive Decline
It has been observed that some elderly people suffer temporary and sometimes permanent cognitive decline following a lengthy operation. Researchers at the University of South Florida and Vanderbilt University suspected that this might be due to excessive exposure to oxygen [4]. Typically, during an operation, people are often administered high doses of oxygen, even as much as 100% oxygen. The researchers conducted an experiment on young adult mice, which had been engineered to be predisposed towards Alzheimer's but had not yet suffered cognitive decline. They did however already have amyloid-beta deposits in their brains. The re-engineered mice, as well as a control group that did not have the Alzheimer's susceptibility gene, were exposed to 100-percent oxygen for a period of three hours, three times over the course of several months, simulating repeated operations. They found that the Alzheimer's pre-disposed mice suffered significant cognitive decline following the oxygen exposure, by contrast with the control mice.
This is a strong indication that the excessive oxygen exposure during operations is causing oxidative damage in the Alzheimer's brain. Given the arguments I have presented above, this result makes good sense. The brain, by converting to anaerobic metabolism for generating energy (with help from amyloid-beta) is trying its best to avoid exposing the fatty acids and cholesterol to oxidative damage. But an extremely high concentration of oxygen in the blood makes it very difficult to protect the fats and cholesterol during transport through the blood, and also probably causes an unavoidable increase in oxygen uptake and therefore exposure within the brain itself.
This is a strong indication that the excessive oxygen exposure during operations is causing oxidative damage in the Alzheimer's brain. Given the arguments I have presented above, this result makes good sense. The brain, by converting to anaerobic metabolism for generating energy (with help from amyloid-beta) is trying its best to avoid exposing the fatty acids and cholesterol to oxidative damage. But an extremely high concentration of oxygen in the blood makes it very difficult to protect the fats and cholesterol during transport through the blood, and also probably causes an unavoidable increase in oxygen uptake and therefore exposure within the brain itself.
14.Fats are a Healthy Choice
You would practically have to be as isolated as an Australian Aborigine not to have absorbed the message that dietary fats, particularly saturated fats, are unhealthy. I am extremely confident that this message is false, but it is nearly impossible to turn the opinion tide due to its pervasive presence. Most people don't question why fats are bad; they assume that researchers must have done their homework, and they trust the result.
To say that the current situation with regard to dietary fats is confusing would be an understatement. We are repeatedly told to keep our total fat intake down to, ideally, 20% of our total calories. This is difficult to achieve, and I believe it is misguided advice. In direct contradiction to this "low-fat" goal, we are encouraged to consume as much as possible of the "good" kinds of fats. Fortunately, the message is finally becoming widely embraced that omega-3 fats are healthy and that trans fats are extremely unhealthy. DHA (docosahexaenoic acid) is an omega-3 fat that is found in large quantities in the healthy brain. In the diet, it is available mainly from cold water fish, but eggs and dairy are also good sources. Trans fats are generated by a high-heat process that hydrolyzes polyunsaturated fats into a more stable configuration, which increases their shelf life but makes them so unnatural they almost can no longer be called a food. Trans fats are extremely damaging both to heart and brain health. A high consumption of trans fats has recently been shown to increase the risk of Alzheimer's [41]. Trans fats are especially prevalent in highly processed foods -- particularly when fats are converted to a powdered form.
We are told to avoid saturated fats, mainly because they have appeared, from empirical evidence, to be more likely to raise LDL levels than unsaturated fats. Yet these fats are less susceptible to oxidation, and this may be why they show up in LDL -- because they are of higher quality and therefore should preferentially be delivered to the tissues for functional roles rather than as fuel (i.e., free fatty acids). Coconut oil, a saturated fat, has been shown to benefit Alzheimer's patients [42]. And high-fat dairy (also highly saturated) has been shown to be beneficial both to fertility among women [10] and, remarkably, to heart disease [37][22].
Despite the widespread belief that fats (particularly saturated fats) are unhealthy, an article that appeared in the American Journal of Clinical Nutrition in 2004 [37] claims that, for a group of post-menopausal women, a high-fat, high-saturated-fat diet affords better protection from coronary artery disease than a low-fat (25% of calories from fats) diet. The subjects in the study were obese women with coronary artery disease. Most of them had high blood pressure, and many had diabetes. They fit the profile for metabolic syndrome that I have previously argued is a direct consequence of a prolonged low-fat high-carb diet. I am gratified to see that my hypothesis that an increase in fat intake would decrease their risk of heart disease has been verified by a carefully controlled study.
Another investigation where fats were shown to afford protection against heart disease has just been completed. It involved a long-term study of a large number of Swedish men [22]. The authors looked at low- vs high-fat dairy, as well as consumption of fruits and vegetables, meats, grains, etc. The only statistically significant result that afforded protection from heart disease was a combination of high-fat dairy and lots of fruits and vegetables. Fruits and vegetables with low-fat dairy afforded no protection.
I suspect one of the critical nutrients the fruits and vegetables provide is antioxidants that help prolong the life of the fats. Other excellent sources of antioxidants include richly colored fruits like berries and tomatoes, coffee, green tea, and dark chocolate, and several spices, most especially cinnamon and turmeric (a major ingredient of curry). These should be consumed in abundance along with fats for optimal results.
Polyunsaturated fats such as corn oil and canola oil are unhealthy for the brain precisely because they are unsaturated. There are two major problems: (1) they have a low melting point, which means that, if they are used for frying they will be converted to trans fats, which are extremely unhealthy, and (2) they are much more susceptible to becoming rancid (oxidized) at room temperature than saturated fats, i.e., they have a shorter shelf life.
Researchers in Germany recently conducted an ingenious experiment designed to determine how the degree of freshness of polyunsaturated fats affects the metabolism of those fats in female lactating rats [43]. They divided female rats into two groups, and the only difference between the test group and the controls was that the test group was given fats that had been left in a relatively warm place for 25 days, which caused considerable oxidative damage, whereas the controls were fed fresh fats instead. The rats' unusual diet was begun on the day that they gave birth to a litter. The researchers examined the mammary glands and the milk produced by the two groups for apparent differences. They found that the test group's milk was markedly reduced in the amount of fat it contained, and their mammary glands correspondingly took up less fat from the blood supply. One might surmise that the rats' metabolic mechanisms were able to detect oxidative damage to the fats, and therefore rejected them, prefering to do without rather than to risk the consequences of feeding their pups oxidized fats. Consequently, the pups of the test group gained significantly less weight than the control group's pups.
Boxed items like cookies and crackers that contain processed polyunsaturated fats are doctored with antioxidants and even antibiotics to protect them from spoiling. Once they're consumed, however, they still have to be protected from going rancid. Biochemical laws work the same way whether inside or outside the body. There are plenty of bacteria throughout the body that would be eager to take up house-keeping in rancid fats. The body has devised all kinds of strategies for protecting fats from oxidation (becoming rancid) and from attack by bacteria. But its task is rendered much easier for saturated rather than unsaturated fats, and for fresh rather than stale fats.
If we stop trying to get by on as few fats as possible in the diet, then we don't have to become so preoccupied with getting the "right" kinds of fats. If the body is supplied with an overabundance of fats, it can pick and choose to find the perfect fat to match each particular need; excess or defective fats can just be used as fuel, where it's not very important which fat it is, as long as it can be broken down to release energy.
To say that the current situation with regard to dietary fats is confusing would be an understatement. We are repeatedly told to keep our total fat intake down to, ideally, 20% of our total calories. This is difficult to achieve, and I believe it is misguided advice. In direct contradiction to this "low-fat" goal, we are encouraged to consume as much as possible of the "good" kinds of fats. Fortunately, the message is finally becoming widely embraced that omega-3 fats are healthy and that trans fats are extremely unhealthy. DHA (docosahexaenoic acid) is an omega-3 fat that is found in large quantities in the healthy brain. In the diet, it is available mainly from cold water fish, but eggs and dairy are also good sources. Trans fats are generated by a high-heat process that hydrolyzes polyunsaturated fats into a more stable configuration, which increases their shelf life but makes them so unnatural they almost can no longer be called a food. Trans fats are extremely damaging both to heart and brain health. A high consumption of trans fats has recently been shown to increase the risk of Alzheimer's [41]. Trans fats are especially prevalent in highly processed foods -- particularly when fats are converted to a powdered form.
We are told to avoid saturated fats, mainly because they have appeared, from empirical evidence, to be more likely to raise LDL levels than unsaturated fats. Yet these fats are less susceptible to oxidation, and this may be why they show up in LDL -- because they are of higher quality and therefore should preferentially be delivered to the tissues for functional roles rather than as fuel (i.e., free fatty acids). Coconut oil, a saturated fat, has been shown to benefit Alzheimer's patients [42]. And high-fat dairy (also highly saturated) has been shown to be beneficial both to fertility among women [10] and, remarkably, to heart disease [37][22].
Despite the widespread belief that fats (particularly saturated fats) are unhealthy, an article that appeared in the American Journal of Clinical Nutrition in 2004 [37] claims that, for a group of post-menopausal women, a high-fat, high-saturated-fat diet affords better protection from coronary artery disease than a low-fat (25% of calories from fats) diet. The subjects in the study were obese women with coronary artery disease. Most of them had high blood pressure, and many had diabetes. They fit the profile for metabolic syndrome that I have previously argued is a direct consequence of a prolonged low-fat high-carb diet. I am gratified to see that my hypothesis that an increase in fat intake would decrease their risk of heart disease has been verified by a carefully controlled study.
Another investigation where fats were shown to afford protection against heart disease has just been completed. It involved a long-term study of a large number of Swedish men [22]. The authors looked at low- vs high-fat dairy, as well as consumption of fruits and vegetables, meats, grains, etc. The only statistically significant result that afforded protection from heart disease was a combination of high-fat dairy and lots of fruits and vegetables. Fruits and vegetables with low-fat dairy afforded no protection.
I suspect one of the critical nutrients the fruits and vegetables provide is antioxidants that help prolong the life of the fats. Other excellent sources of antioxidants include richly colored fruits like berries and tomatoes, coffee, green tea, and dark chocolate, and several spices, most especially cinnamon and turmeric (a major ingredient of curry). These should be consumed in abundance along with fats for optimal results.
Polyunsaturated fats such as corn oil and canola oil are unhealthy for the brain precisely because they are unsaturated. There are two major problems: (1) they have a low melting point, which means that, if they are used for frying they will be converted to trans fats, which are extremely unhealthy, and (2) they are much more susceptible to becoming rancid (oxidized) at room temperature than saturated fats, i.e., they have a shorter shelf life.
Researchers in Germany recently conducted an ingenious experiment designed to determine how the degree of freshness of polyunsaturated fats affects the metabolism of those fats in female lactating rats [43]. They divided female rats into two groups, and the only difference between the test group and the controls was that the test group was given fats that had been left in a relatively warm place for 25 days, which caused considerable oxidative damage, whereas the controls were fed fresh fats instead. The rats' unusual diet was begun on the day that they gave birth to a litter. The researchers examined the mammary glands and the milk produced by the two groups for apparent differences. They found that the test group's milk was markedly reduced in the amount of fat it contained, and their mammary glands correspondingly took up less fat from the blood supply. One might surmise that the rats' metabolic mechanisms were able to detect oxidative damage to the fats, and therefore rejected them, prefering to do without rather than to risk the consequences of feeding their pups oxidized fats. Consequently, the pups of the test group gained significantly less weight than the control group's pups.
Boxed items like cookies and crackers that contain processed polyunsaturated fats are doctored with antioxidants and even antibiotics to protect them from spoiling. Once they're consumed, however, they still have to be protected from going rancid. Biochemical laws work the same way whether inside or outside the body. There are plenty of bacteria throughout the body that would be eager to take up house-keeping in rancid fats. The body has devised all kinds of strategies for protecting fats from oxidation (becoming rancid) and from attack by bacteria. But its task is rendered much easier for saturated rather than unsaturated fats, and for fresh rather than stale fats.
If we stop trying to get by on as few fats as possible in the diet, then we don't have to become so preoccupied with getting the "right" kinds of fats. If the body is supplied with an overabundance of fats, it can pick and choose to find the perfect fat to match each particular need; excess or defective fats can just be used as fuel, where it's not very important which fat it is, as long as it can be broken down to release energy.
15. Summary of Alzheimer's Essay
This is an exciting time for Alzheimer's research, as new and surprising discoveries are coming out at a rapid pace, and evidence is mounting to support the notion that Alzheimer's is a nutritional deficiency disease. It is an indication of how much progress has been made in recent years to note that 42% of the references in this essay were published in 2008 or 2009. A popular new theory is that Alzheimer's may grow out of an impaired ability to metabolize glucose in the brain. The term "type-3 diabetes" has been coined to describe this defect, which often appears long before any symptoms of Alzheimer's. A shift from aerobic towards anaerobic glucose metabolism in the brain seems to be a harbinger of Alzheimer's later in life, but I argue that the reason for this shift is both to provide a basic ingredient (pyruvate) from which to synthesize fatty acids, while simultaneously protecting them from potentially damaging oxidation. The ApoE-4 allele, which is associated with increased risk to Alzheimer's, clearly implicates defects in fat and cholesterol transport, and the remarkable 6-fold reduction in the amount of fatty acids present in the cerebrospinal fluid of Alzheimer's patients [38] speaks loudly the message that fat insufficiency is a key part of the picture. The observation that the myelin is degraded in the frontal lobes of the brains of people possessing the apoE-4 allele further substantiates the theory that the myelin repair mechanism is defective.
Cholesterol obviously plays a vital role in brain function. A whopping 25% of the total cholesterol in the body is found in the brain, and it is present in abundance both in the synapses and in the myelin sheath. The cholesterol in both of these places has been shown to play an absolutely essential role in signal transport and in growth and repair.
Given the strong positive role played by cholesterol, it can only be assumed that statin drugs would increase the risk of developing Alzheimer's. However, the statin industry has been remarkably successful thus far in hiding this painful fact. They have managed to make much of the observation that high cholesterol much earlier in life is associated with an increased risk to Alzheimer's thirty years later. Yet they offer not a single study, not even a retrospective study, to substantiate any claim that actively reducing cholesterol through statin therapy would improve the situation for these people. In fact, most damningly, the statin usage evidence that would answer the question was "unavailable" to the researchers who conducted the seminal study.
Beatrice Golomb is an M.D. Ph.D. who heads up the UCSD Statin Study group, a research team who are actively investigating the risk-benefit balance of statin drugs. She is increasingly becoming convinced that statin drugs should not be recommended for the elderly: that in their case the risks clearly outweigh the benefits. She makes a strong case for this position in an on-line article available here [15]. The section on Alzheimer's is particularly compelling, and it points out the pitfalls in relying on previous studies done by the statin industry, where often those who have memory problems as side-effects of the statin drugs are excluded from the study, so that the results end up inappropriately biased in favor of statins. In summary, she wrote: "It must be emphasized that the randomized trial evidence has, to date, uniformly failed to show cognitive benefits by statins and has supported no effect or frank and significant harm to cognitive function."
In addition to refusing to take statin therapy, another way in which an individual can improve their odds against Alzheimer's is to consume plenty of dietary fats. It seems odd to suddenly switch from a "healthy" low-fat diet to an extremely high fat ketogenic diet, once a diagnosis of Alzheimer's is made. A ketogenic diet consists, ideally, of 88% fat, 10% protein, and 2% carbohydrate [11]. That is to say, it is absurdly high in fat content. It seems much more reasonable to aim for something like 50% fat, 30% protein, and 20% carbohydrate, so as to pro-actively defend against Alzheimer's.
I highly recommend a recent book written by the pediatric brain surgeon, Larry McCleary, M.D., called The Brain Trust Program [33]. This book gives a wealth of fascinating information about the brain, as well as specific recommendations for ways to improve cognitive function and avert later Alzheimer's. Most significantly, he recommends a diet that is high in cholesterol and animal fats, including an abundance of fish, seafood, meat, and eggs. He also recommends coconuts, almonds, avocados and cheese, all foods that contain a significant amount of fat, while encouraging the avoidance of "empty carbs." His knowledge on this subject grew out of his interest in helping his young patients heal more rapidly after brain trauma.
Our nation is currently bracing itself for an onslaught of Alzheimer's, at a time when baby boomers are approaching retirement, and our health care system is already in a crisis of escalating costs and shrinking funds. We can not afford the high cost of caring for the swelling population of Alzheimer's patients that our current practices of low-fat diet and ever expanding statin usage are promoting.
Cholesterol obviously plays a vital role in brain function. A whopping 25% of the total cholesterol in the body is found in the brain, and it is present in abundance both in the synapses and in the myelin sheath. The cholesterol in both of these places has been shown to play an absolutely essential role in signal transport and in growth and repair.
Given the strong positive role played by cholesterol, it can only be assumed that statin drugs would increase the risk of developing Alzheimer's. However, the statin industry has been remarkably successful thus far in hiding this painful fact. They have managed to make much of the observation that high cholesterol much earlier in life is associated with an increased risk to Alzheimer's thirty years later. Yet they offer not a single study, not even a retrospective study, to substantiate any claim that actively reducing cholesterol through statin therapy would improve the situation for these people. In fact, most damningly, the statin usage evidence that would answer the question was "unavailable" to the researchers who conducted the seminal study.
Beatrice Golomb is an M.D. Ph.D. who heads up the UCSD Statin Study group, a research team who are actively investigating the risk-benefit balance of statin drugs. She is increasingly becoming convinced that statin drugs should not be recommended for the elderly: that in their case the risks clearly outweigh the benefits. She makes a strong case for this position in an on-line article available here [15]. The section on Alzheimer's is particularly compelling, and it points out the pitfalls in relying on previous studies done by the statin industry, where often those who have memory problems as side-effects of the statin drugs are excluded from the study, so that the results end up inappropriately biased in favor of statins. In summary, she wrote: "It must be emphasized that the randomized trial evidence has, to date, uniformly failed to show cognitive benefits by statins and has supported no effect or frank and significant harm to cognitive function."
In addition to refusing to take statin therapy, another way in which an individual can improve their odds against Alzheimer's is to consume plenty of dietary fats. It seems odd to suddenly switch from a "healthy" low-fat diet to an extremely high fat ketogenic diet, once a diagnosis of Alzheimer's is made. A ketogenic diet consists, ideally, of 88% fat, 10% protein, and 2% carbohydrate [11]. That is to say, it is absurdly high in fat content. It seems much more reasonable to aim for something like 50% fat, 30% protein, and 20% carbohydrate, so as to pro-actively defend against Alzheimer's.
I highly recommend a recent book written by the pediatric brain surgeon, Larry McCleary, M.D., called The Brain Trust Program [33]. This book gives a wealth of fascinating information about the brain, as well as specific recommendations for ways to improve cognitive function and avert later Alzheimer's. Most significantly, he recommends a diet that is high in cholesterol and animal fats, including an abundance of fish, seafood, meat, and eggs. He also recommends coconuts, almonds, avocados and cheese, all foods that contain a significant amount of fat, while encouraging the avoidance of "empty carbs." His knowledge on this subject grew out of his interest in helping his young patients heal more rapidly after brain trauma.
Our nation is currently bracing itself for an onslaught of Alzheimer's, at a time when baby boomers are approaching retirement, and our health care system is already in a crisis of escalating costs and shrinking funds. We can not afford the high cost of caring for the swelling population of Alzheimer's patients that our current practices of low-fat diet and ever expanding statin usage are promoting.
Appendix of Alzheimer's Essay
In this appendix, I include the full abstract of two papers that are relevant to the theory presented here. The first is the abstract of reference [19] in [46], which is reference [44] here [see the section on statin drugs above for context]:
Abstract, "Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer's disease:"
"This paper reviews epidemiological and clinical trials data about whether statin use reduces the risk of Alzheimer's disease (AD). The available information has come in three waves. The initial, mostly cross-sectional observational reports suggested that statins might prevent dementia. Next, two large clinical trials with cognitive add-on studies showed no benefit and neither did the third wave, again with observational studies. The latter were mostly longitudinal, and were critical of the first studies for not adequately addressing confounding by indication (i.e. that patients with dementia would be denied statins). Most recently, new data from the Canadian Study of Health and Aging have produced a mixed result. While methodological considerations are clearly important in understanding why the reports are so variable, there might also be merit in differentiating between statins, based on their presumed - and variable - mechanisms of action in dementia prevention, before concluding that the initial reports are entirely artefactual. Still, the first reports appear to have overestimated the extent of protection, so that unless there are important effects achievable with specific statins, a more than a modest role for statins in preventing AD seems unlikely."
The second abstract is taken from reference [28], on the "alternative hypothesis" that amyloid-beta is protective rather than detrimental to Alzheimer's, i.e., that it is a "protective response to neuronal insult:"
Abstract, "Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses:"
"For nearly 20 years, the primary focus for researchers studying Alzheimer disease has been centered on amyloid-beta, such that the amyloid cascade hypothesis has become the "null hypothesis." Indeed, amyloid-beta 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-beta 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-beta, 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-beta 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."
Abstract, "Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer's disease:"
"This paper reviews epidemiological and clinical trials data about whether statin use reduces the risk of Alzheimer's disease (AD). The available information has come in three waves. The initial, mostly cross-sectional observational reports suggested that statins might prevent dementia. Next, two large clinical trials with cognitive add-on studies showed no benefit and neither did the third wave, again with observational studies. The latter were mostly longitudinal, and were critical of the first studies for not adequately addressing confounding by indication (i.e. that patients with dementia would be denied statins). Most recently, new data from the Canadian Study of Health and Aging have produced a mixed result. While methodological considerations are clearly important in understanding why the reports are so variable, there might also be merit in differentiating between statins, based on their presumed - and variable - mechanisms of action in dementia prevention, before concluding that the initial reports are entirely artefactual. Still, the first reports appear to have overestimated the extent of protection, so that unless there are important effects achievable with specific statins, a more than a modest role for statins in preventing AD seems unlikely."
The second abstract is taken from reference [28], on the "alternative hypothesis" that amyloid-beta is protective rather than detrimental to Alzheimer's, i.e., that it is a "protective response to neuronal insult:"
Abstract, "Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses:"
"For nearly 20 years, the primary focus for researchers studying Alzheimer disease has been centered on amyloid-beta, such that the amyloid cascade hypothesis has become the "null hypothesis." Indeed, amyloid-beta 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-beta 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-beta, 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-beta 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."
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