High-fat Diet

In a large Mayo Clinic study, self-reported diet was found to be significantly associated with the risk of seniors developing mild cognitive impairment or dementia over a four-year period.

The study involved 1,230 older adults (70-89) who completed a 128-item food-frequency questionnaire about their diet during the previous year. Of these, around three-quarters (937) showed no signs of cognitive impairment at the beginning of the study period, and were asked to return for follow-up cognitive assessments. These assessments took place every 15 months. After about four years, 200 (21%) had developed mild cognitive impairment (MCI) or dementia.

The likelihood of cognitive deterioration was significantly affected by the type of diet. Those with the highest carbohydrate intake were nearly twice as likely to develop cognitive impairment compared to those with the lowest carbohydrate consumption, and when total fat and protein intake were taken into account, they were 3.6 times likelier to develop impairment.

Those with the highest sugar intake were 1.5 times more likely to develop cognitive impairment.

But — a finding that will no doubt surprise many — those with the highest fat consumption were 42% less likely to develop cognitive impairment, compared to those with the lowest level of fats.

Less surprisingly, those with highest intake of protein had a reduced risk of 21%.

In other words, the worst diet you can have, if you want to keep your brain healthy, is one that receives most of its calories from carbohydrates and sugar, and relatively little from fats and protein.

The findings about carbs, sugar, and protein are consistent with other research. The finding regarding fats is somewhat more surprising. The inconsistency may lie in the type of fat. Research implicating high-fat diets as a risk factor in Alzheimer’s have used saturated fats. Diets high in olive oil, on the other hand, have been found to be beneficial.

It seems likely that the danger of carbs and too much sugar lies in the effects on glucose and insulin metabolism. Saturated fats also interfere with glucose metabolism. Alzheimer’s has sometimes been called Type 3 diabetes, because of its association with insulin problems.

Roberts RO, Roberts LA, Geda YE, Cha RH, Pankratz VS, O'Connor HM, Knopman DS, Petersen RC. 2012. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. Journal of Alzheimers Disease, 32(2), 329-39.

A study designed to compare the relative benefits of exercise and diet control on Alzheimer’s pathology and cognitive performance has revealed that while both are beneficial, exercise is of greater benefit in reducing Alzheimer’s pathology and cognitive impairment.

The study involved mice genetically engineered with a mutation in the APP gene (a familial risk factor for Alzheimer’s), who were given either a standard diet or a high-fat diet (60% fat, 20% carbohydrate, 20% protein vs 10% fat, 70% carbohydrate, 20% protein) for 20 weeks (from 2-3 to 7-8 months of age). Some of the mice on the high-fat diet spent the second half of that 20 weeks in an environmentally enriched cage (more than twice as large as the standard cage, and supplied with a running wheel and other objects). Others on the high-fat diet were put back on a standard diet in the second 10 weeks. Yet another group were put on a standard diet and given an enriched cage in the second 10 weeks.

Unsurprisingly, those on the high-fat diet gained significantly more weight than those on the standard diet, and exercise reduced that gain — but not as much as diet control (i.e., returning to a standard diet) did. Interestingly, this was not the result of changes in food intake, which either stayed the same or slightly increased.

More importantly, exercise and diet control were roughly equal in reversing glucose intolerance, but exercise was more effective than diet control in ameliorating cognitive impairment. Similarly, while amyloid-beta pathology was significantly reduced in both exercise and diet-control conditions, exercise produced the greater reduction in amyloid-beta deposits and level of amyloid-beta oligomers.

It seems that diet control improves metabolic disorders induced by a high-fat diet — conditions such as obesity, hyperinsulinemia and hypercholesterolemia — which affects the production of amyloid-beta. However exercise is more effective in tackling brain pathology directly implicated in dementia and cognitive decline, because it strengthens the activity of an enzyme that decreases the level of amyloid-beta.

Interestingly, and somewhat surprisingly, the combination of exercise and diet control did not have a significantly better effect than exercise alone.

The finding adds to the growing pile of evidence for the value of exercise in maintaining a healthy brain in later life, and helps explain why. Of course, as I’ve discussed on several occasions, we already know other mechanisms by which exercise improves cognition, such as boosting neurogenesis.

A rat study has shown how a diet high in fructose (from corn syrup, not the natural levels that occur in fruit) impairs brain connections and hurts memory and learning — and how omega-3 fatty acids can reduce the damage.

We know that these unnaturally high levels of fructose can hurt the brain indirectly through their role in diabetes and obesity, but this new study demonstrates that it also damages the brain directly.

In the study, two groups of rats consumed a fructose solution as drinking water for six weeks. One of these groups also received omega-3 fatty acids in the form of flaxseed oil and DHA. Both groups trained on a maze twice daily for five days before starting the experimental diet. After the six weeks of the diet, the rats were put in the maze again.

Those who didn’t receive the omega-3 oils navigated the maze much more slowly than the second group, and their brains showed a decline in synaptic activity. They also showed signs of resistance to insulin. Indications were that insulin had lost much of its power to regulate synaptic function.

It’s suggested that too much fructose could block insulin's ability to regulate how cells use and store sugar for the energy required for processing information.

It’s estimated that the average American consumes more than 40 pounds of high-fructose corn syrup per year.

The findings are consistent with research showing an association between metabolic syndrome and poorer cognitive function, and help explain the mechanism. They also support the consumption of omega-3 fatty acids as a preventative or ameliorative strategy.

Data from the Women's Health Study, involving 6,183 older women (65+), has found that it isn’t the amount of fat but the type of fat that is associated with cognitive decline. The women were given three cognitive function tests at two-yearly intervals, and filled out very detailed food frequency surveys at the beginning of the study.

Women who consumed the highest amounts of saturated fat (such as that from animals) had significantly poorer cognitive function compared to those who consumed the lowest amounts. Women who instead had a high intake of monounsaturated fats (such as olive oil) had better cognitive scores over time. Total fat, polyunsaturated fat, and trans fat, were not associated with cognitive performance.

The findings are consistent with research associating the Mediterranean diet (high in olive oil) with lower Alzheimer’s risk, and studies linking diets high in saturated fats with greater cognitive decline.

I have reported often on studies pointing to obesity as increasing your risk of developing dementia, and on the smaller evidence that calorie restriction may help fight age-related cognitive decline and dementia (and help you live longer). A new mouse study helps explain why eating less might help the brain.

It turns out that a molecule called CREB-1 is triggered by calorie restriction (defined as only 70% of normal consumption). cAMP Response Element Binding (CREB) protein is an essential component of long-term memory formation, and abnormalities in the expression of CREB have been reported in the brains of Alzheimer’s patients. Restoring CREB to Alzheimer’s mice has been shown to improve learning and memory impairment.

Animal models have also indicated a role for CREB in the improvements in learning and memory brought about by physical exercise. CREB seems to be vital for adult neurogenesis.

The current study found that, when CREB1 was missing (in mice genetically engineered to lack this molecule), calorie restriction had no cognitive benefits. CREB deficiency in turn drastically reduced the expression of Sirt-1. These proteins have been implicated in cardiac function, DNA repair and genomic stability (hence the connection to longevity). More recently, Sirt-1 has also been found to modulate synaptic plasticity and memory formation — an effect mediated by CREB. This role in regulating normal brain function appears to be quite separate from its cell survival functions.

The findings identify a target for drugs that could produce the same cognitive (and longevity) benefits without the need for such strict food reduction.

Reducing your eating and drinking to 70% of normal intake is a severe reduction. Recently, researchers at the National Institute on Ageing in Baltimore have suggested that the best way to cut calories to achieve cognitive benefits was to virtually fast (down to around 500 calories) for two days a week, while eating as much as you want on the other days. Their animal experiments indicate that timing is a crucial element if cognitive benefits are to accrue.

Another preliminary report, this time from the long-running Mayo Clinic study of aging, adds to the evidence that lower consumption reduces the risk of serious cognitive impairment. The first analysis of data has revealed that the risk of developing mild cognitive impairment more than doubled for those in the highest food consumption group (daily calorie consumption between 2,143 and 6,000) compared to those in the lowest (between 600 and 1,526 calories).

Calorie consumption was taken from food questionnaires in which respondents described their diets over the previous year, so must be taken with a grain of salt. Additionally, the analysis didn’t take into account types of food and beverages, or other lifestyle factors, such as exercise. Further analysis will investigate these matters in more depth.

The study involved 1,233 older adults, aged 70 to 89. Of these, 163 were found to have MCI.

None of this should be taken as a recommendation for severely restricting your diet. Certainly such behavior should not be undertaken without the approval of your doctor, but in any case, calorie restriction is only part of a much more complex issue concerning diet. I look forward to hearing more from the Mayo Clinic study regarding types of foods and interacting factors.

[2681] Fusco S, Ripoli C, Podda MV, Ranieri SC, Leone L, Toietta G, McBurney MW, Schütz G, Riccio A, Grassi C, et al. A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction. Proceedings of the National Academy of Sciences [Internet]. 2012 ;109(2):621 - 626. Available from: http://www.pnas.org/content/109/2/621.abstract

The findings from the National Institute on Aging were presented at the annual meeting of the American Association for the Advancement of Science in Vancouver.

Geda, Y., Ragossnig, M., Roberts, L.K., Roberts, R., Pankratz, V., Christianson, T., Mielke, M., Boeve, B., Tangalos, E. & Petersen, R. 2012. Caloric Intake, Aging, and Mild Cognitive Impairment: A Population-Based Study. To be presented April 25 at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

Dietary changes affect levels of biomarkers associated with Alzheimer's

In a study involving 20 healthy older adults (mean age 69.3) and 29 older adults who had amnestic mild cognitive impairment (mean age 67.6), half the participants were randomly assigned to a high–saturated fat/high–simple carbohydrate diet (HIGH) and half to a low–saturated fat/low–simple carbohydrate diet (LOW) for four weeks, in order to investigate the effects on biomarkers associated with Alzheimer’s.

For the healthy participants, the LOW diet decreased the level of amyloid-beta 42 in the cerebrospinal fluid, while the HIGH diet increased its level. The HIGH diet also lowered the CSF insulin concentration. For those with aMCI, the LOW diet increased the levels of amyloid-beta 42 and increased the CSF insulin concentration. For both groups, the level of apolipoprotein E in the CSF increased in the LOW diet and decreased in the HIGH diet.

For both groups, the LOW diet improved performance on delayed visual recall tests, but didn’t affect scores on other cognitive measures (bear in mind that the diet was only followed for a month).

The researchers suggest that the different results of the unhealthy diet in participants with aMCI may be due to the diet’s short duration. The fact that diet was bringing about measurable changes in CSF biomarkers so quickly, and that the HIGH diet moved healthy brains in the direction of Alzheimer’s, speaks to the potential of dietary intervention.

Why coffee helps protect against Alzheimer's disease

Support for the value of coffee in decreasing the risk of Alzheimer’s comes from a mouse study, which found that an as yet unidentified ingredient in coffee interacts with caffeine in such a way that blood levels of a growth factor called GCSF (granulocyte colony stimulating factor) increases. GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice.

The finding points to the value of caffeinated coffee, as opposed to decaffeinated coffee or to other sources of caffeine. Moreover, only "drip" coffee was used; the researchers caution that they don’t know whether instant caffeinated coffee would provide the same GCSF response.

There are three ways that GCSF seems to improve memory performance in the Alzheimer's mice: by recruiting stem cells from bone marrow to enter the brain and remove beta-amyloid protein; by increasing the growth of new synapses; by increasing neurogenesis.

The amount of coffee needed to provide this protection, however, is estimated to be about 4 to 5 cups a day. The researchers also believe that this daily coffee intake is best begun at least by middle age (30s – 50s), although starting even in older age does seem to have some protective effect.

Weirdly (I thought), the researchers remarked that "The average American gets most of their daily antioxidants intake through coffee". Perhaps this points more to the defects in their diet than to the wonders of coffee! But the finding is consistent with other research showing an association between moderate consumption of coffee and decreased risk of Parkinson's disease, Type II diabetes and stroke.

A just-completed clinical trial has investigated GCSF treatment to prevent Alzheimer's in patients with mild cognitive impairment, and the results should be known soon.

[2442] Bayer-Carter JL, Green PS, Montine TJ, VanFossen B, Baker LD, Watson SG, Bonner LM, Callaghan M, Leverenz JB, Walter BK, et al. Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment. Arch Neurol [Internet]. 2011 ;68(6):743 - 752. Available from: http://archneur.ama-assn.org/cgi/content/abstract/68/6/743

Cao, C., Wang, L., Lin, X., Mamcarz, M., Zhang, C., Bai, G., Nong, J., Sussman, S. & Arendash, G.  2011.Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer's Mice. Journal of Alzheimer's Disease, 25(2), 323-335.

A number of studies have provided evidence that eating breakfast has an immediate benefit for cognitive performance in children. Now a new study suggests some “good” breakfasts are better than others.

A Japanese study of 290 healthy, well-nourished children, has revealed that those whose breakfast staple was white rice had a significantly larger ratio of gray matter in their brains, and several significantly larger regions, including the left superior temporal gyrus and bilateral caudate. Those who habitually ate white bread had significantly larger regional gray and white matter volumes of several regions, including the orbitofrontal gyri, right precentral gyrus and postcentral gyrus. Overall IQ scores, and scores on the perceptual organization subcomponent in particular, were significantly higher for the rice group.

One possible reason for the difference may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. There is also a difference in fat content, with those eating white bread typically consuming more fat than those eating a rice-based breakfast. High levels of fat have been shown to reduce the expression of BDNF.

Regardless of the reason for the difference, the fact that breakfast staple type affects brain size and cognitive function in healthy children points to the importance of good nutrition during the years of brain development.

A very large study of older women has found that although there was a small downward trend in cognitive function (as measured by the MMSE) with increasing obesity, this trend was almost entirely driven by those with a waist-hip ratio below 0.78 — that is, for women who carry excess weight around their hips, known as pear shapes (as opposed to carrying it around the waist, called apple shapes). The study of 8,745 post-menopausal women (aged 65-79) found a drop of around 2 points on the 100-point MMSE for those with a BMI over 40 compared to those who were of normal weight, after controlling for such variables as education, diabetes, heart disease and hypertension, all of which were also significantly associated with BMI and MMSE score. Because 86% of the participants were white, and women belonging to other ethnic groups were not equally distributed between BMI categories, only data from white women were used. Some 70% of the participants were overweight (36%) or obese (34%).

Fat around the middle is thought to make more estrogen, which protects cognitive function. However, although depositing fat around the waist may be better for the brain, it is said to increase the risk of cancer, diabetes and heart disease.

Studies on the roundworm C. elegans have revealed that the molecules required for learning and memory are the same from C. elegans to mammals, suggesting that the basic mechanisms underlying learning and memory are ancient, and that this animal can serve as a testing ground for treatments for age-related memory loss. Intriguingly, a comparison of two known regulators of longevity — reducing calorie intake and reducing activity in the insulin-signaling pathway (achieved through genetic manipulation) — has found that these two treatments produce very different effects on memory. While dietary restriction impaired memory in early adulthood, it maintained memory with age. On the other hand, reduced insulin signaling improved early adult memory performance but failed to preserve it with age. These different effects appear to be linked to expression of CREB, a protein known to be important for long-term memory. Young roundworms with defective insulin receptors had higher levels of CREB protein, while those worms genetically altered to eat less had low levels, but the level did not diminish with age. These findings add to our understanding of why memory declines with age.

A study comparing the brains 32 adult women with Anorexia Nervosa and 21 healthy women has revealed that when the women with anorexia were in a state of starvation they had less brain tissue (especially in grey matter) compared to the healthy women. Those who had the illness the longest had the greatest reductions in brain volume when underweight. Happily, these deficits began to reverse after several weeks of weight gain.

Older news items (pre-2010) brought over from the old website

High-fat diet affects physical and memory abilities of rats after 9 days

A rat study has found that after a mere 9 days of eating a high-fat diet (55% of calories as fat, compared to their normal very low-fat diet of 7.5% of calories as fat)), rats were dramatically slower to run a maze and made more mistakes. The reductions in performance were correlated with increased levels of a protein that is involved in the process of burning food stuffs for energy in the cells, reducing the efficiency of the heart and muscles, and with an increase in heart size, probably because it had to pump more blood around the body to get the necessary oxygen to the muscles (and brain). The increase in fat is of course extremely high for the rats, given that their normal diet is very low in fat; however, the level is not out of keeping with a human unhealthy diet.

[1160] Murray AJ, Knight NS, Cochlin LE, McAleese S, Deacon RMJ, Rawlins NJP, Clarke K. Deterioration of physical performance and cognitive function in rats with short-term high-fat feeding. FASEB J. [Internet]. 2009 ;23(12):4353 - 4360. Available from: http://www.fasebj.org/cgi/content/abstract/23/12/4353

Full text available at: http://www.fasebj.org/cgi/rapidpdf/fj.09-139691v1.pdf
http://www.eurekalert.org/pub_releases/2009-08/uoc-hda081109.php

Diabetic seniors may experience memory declines after eating high-fat food

Growing evidence links diabetes to cognitive impairment. Now a small study of 16 adults (aged 50 years and older) with type 2 diabetes compared their cognitive performance on three separate occasions, fifteen minutes after consuming different meals. One meal consisted of high fat products – a danish pastry, cheddar cheese and yogurt with added whipped cream; the second meal was only water; and the third was the high-fat meal plus high doses of vitamins C (1000 mg) and E (800 IU) tablets. Researchers found that vitamin supplementation consistently improved recall scores relative to the meal alone, while those who ate the high fat meal without vitamin supplements showed significantly more forgetfulness of words and paragraph information in immediate and time delay recall tests. Those on water meal and meal with vitamins showed similar levels in cognitive performance. The finding indicates not only that diabetics can temporarily further worsen already underlying memory problems associated with the disease by consuming unhealthy meals, but also that this can be remedied by taking high doses of antioxidant vitamins C and E with the meal, suggesting that the effect of high-fat foods si to cause oxidative stress. However, this is hardly a recommended course of action, and the real importance of this finding is that it emphasizes the need for diabetics to consume healthy foods high in antioxidants, like fruits and vegetables. Of course, this is a very small study, and further replication is needed.

[1094] Chui M, Greenwood C. Antioxidant vitamins reduce acute meal-induced memory deficits in adults with type 2 diabetes. Nutrition Research [Internet]. 2008 ;28(7):423 - 429. Available from: http://www.nrjournal.com/article/S0271-5317(08)00090-0/abstract

http://www.eurekalert.org/pub_releases/2008-06/bcfg-swt062408.php

Copper increases cognitive decline in older adults on high-fat diet

A six-year study involving 3,718 Chicago residents age 65 years and older has found that among the 16% who had high levels of saturated and trans fats in their diets, cognitive function deteriorated more rapidly the more copper they had in their diets. Copper intake wasn’t a factor for the rest of the group. Previous studies have found higher levels of copper in the blood of patients with Alzheimer's disease. The finding will need to be confirmed by further research. The dietary recommended allowance of copper for adults is .9 milligrams per day. Organ meats, such as liver, and shellfish are the foods with the highest copper levels, followed by nuts, seeds, legumes, whole grains, potatoes, chocolate and some fruits.

[1129] Morris MC, Evans DA, Tangney CC, Bienias JL, Schneider JA, Wilson RS, Scherr PA. Dietary Copper and High Saturated and trans Fat Intakes Associated With Cognitive Decline. Arch Neurol [Internet]. 2006 ;63(8):1085 - 1088. Available from: http://archneur.ama-assn.org/cgi/content/abstract/63/8/1085

http://www.sciencedaily.com/releases/2006/08/060816013125.htm
http://www.eurekalert.org/pub_releases/2006-08/jaaj-hcd081006.php

Exercise may counteract bad effect of high-fat diet on memory

An animal study has investigated the interaction of diet and exercise on synaptic plasticity (an important factor in learning performance). A diet high in fat reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and impaired performance on spatial learning tasks, but both of these consequences were prevented in those animals with access to voluntary wheel-running. Exercise appeared to interact with the same molecular systems disrupted by the high-fat diet.

[883] Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gómez-Pinilla F. Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience [Internet]. 2004 ;123(2):429 - 440. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14698750

http://journals.bmn.com/jsearch/search/record?uid=NSC.bmn09190_03064522_v0123i02_03007425&rendertype=abstract

Rats on a high-fat diet showed severe impairment on a wide range of learning and memory tasks

Rats on a high-fat diet for three months showed severe impairment on a wide range of learning and memory tasks relative to those animals that consumed the lower fat die. On the basis that the brain needs glucose in order to function, and that saturated fatty acids impede glucose metabolism, the high-fat rats were given high doses of glucose. Glucose significantly improved memory in the high-fat rats, especially long-term memory.

[2402] Greenwood CE, Winocur G. Glucose Treatment Reduces Memory Deficits in Young Adult Rats Fed High-Fat Diets. Neurobiology of Learning and Memory [Internet]. 2001 ;75(2):179 - 189. Available from: http://www.sciencedirect.com/science/article/pii/S1074742700939649

http://www.eurekalert.org/pub_releases/2001-02/BCfG-Rssh-1802101.php

High-fat diets impair memory

Several rodent studies have found evidence that a diet high in fat and empty calories may impair memory.
In one study, young adult male mice were divided into four groups by diet: normal (control) diet, high-saturated-fat diet, high-sugar diet, and diet high in saturated fats and sugar. They were kept on the diet for four months, during which mice on the high-fat and high-fat-&-sugar diets gained significantly more weight than those on the control and high sugar diets. At the end of that time, the mice were tested on a maze task. Mice on the high-fat and high-fat-&-sugar diets performed worse than the other mice. The mice were then exposed to a neurotoxin called kainic acid, which is known to damage nerve cells in the hippocampus. Mice on the high-fat and high-fat-&-sugar diets were significantly more impaired by the neurotoxin.
In another mouse study, obese mice were fed a diet containing about 10% fat for seven months, while control mice were fed standard lab chow containing only 5% fat. On testing, it was found that the obese mice took significantly more trials than the normal-weight mice to both acquire and retain a memory of a foot shock. They also required significantly more trials than control mice to learn to press a lever for milk reinforcement.
A rat study explored whether a diet high in cholesterol and hydrogenated fats affected working memory in middle-aged rats (corresponding to 60 and older for humans). The high-fat, high-cholesterol diet produced significantly higher plasma triglycerides, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol compared with controls. Weight increase and food consumption were similar between the groups. Animals on the high-fat regimen made more errors than animals fed the control diet, especially during the trial that placed the highest demand on their working memory.
Another rat study found that a diet high in fats and carbohydrates worsened cognitive deficits in rats exposed to repeated brief periods of low oxygen during sleep (as experienced by people with sleep apnea).

These studies were reported at the  34th Society for Neuroscience annual meeting in San Diego in October 2004.

http://www.eurekalert.org/pub_releases/2004-10/sfn-hdh102604.php