You can help your brain, especially as it ages, by eating and drinking right
A mouse study adds to evidence that green tea may help protect against age-related cognitive impairment, by showing how one of its components improves neurogenesis.
Green tea is thought to have wide-ranging health benefits, especially in the prevention of cardiovascular disease, inflammatory diseases, and diabetes. These are all implicated in the development of age-related cognitive impairment, so it’s no surprise that regular drinking of green tea has been suggested as one way to help protect against age-related cognitive decline and dementia. A new mouse study adds to that evidence by showing how a particular compound in green tea promotes neurogenesis.
The chemical EGCG, (epigallocatechin-3 gallate) is a known anti-oxidant, but this study shows that it also has a specific benefit in increasing the production of neural progenitor cells. Like stem cells, these progenitor cells can become different types of cell.
Mice treated with EGCG displayed better object recognition and spatial memory than control mice, and this improved performance was associated with the number of progenitor cells in the dentate gyrus and increased activity in the sonic hedgehog signaling pathway (confirming the importance of this pathway in adult neurogenesis in the hippocampus).
The findings add to evidence that green tea may help protect against cognitive impairment and dementia.
 Wang, Y., Li M., Xu X., Song M., Tao H., & Bai Y.
(2012). Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis.
Molecular Nutrition & Food Research. 56(8), 1292 - 1303.
Full text available at http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201200035/abstract
Preliminary results for a small study indicate metabolic syndrome is linked to significantly reduced blood flow in the brain, perhaps explaining its link to cognitive impairment.
I’ve reported before on the growing evidence that metabolic syndrome in middle and old age is linked to greater risk of cognitive impairment in old age and faster decline. A new study shows at least part of the reason.
The study involved 71 middle-aged people recruited from the Wisconsin Registry for Alzheimer's Prevention (WRAP), of whom 29 met the criteria for metabolic syndrome (multiple cardiovascular and diabetes risk factors including abdominal obesity, high blood pressure, high blood sugar and high cholesterol).
Those with metabolic syndrome averaged 15% less blood flow to the brain than those without the syndrome.
One tried and true method of increasing blood flow to the brain is of course through exercise.
The study was presented at the Alzheimer's Association International Conference in Vancouver, Canada by Barbara Bendlin.
A new understanding of why dementia sometimes occurs with HIV, even when treated, may also suggest a new approach to other neurological disorders, including age-related cognitive decline.
HIV-associated dementia occurs in around 30% of untreated HIV-positive patients. Surprisingly, it also is occasionally found in some patients (2-3%) who are being successfully treated for HIV (and show no signs of AIDS).
A new study may have the answer for this mystery, and suggest a solution. Moreover, the answer may have general implications for those experiencing cognitive decline in old age.
The study found that HIV, although it doesn’t directly infect neurons, tries to stop the development of BDNF. Long known to be crucial for memory and learning, the reduced production of mature BDNF results in axons and dendrites shortening — meaning connections between neurons are lost. That in turn, brings about the death of some neurons.
It seems that the virus interferes with the normal process of development in BDNF, whereby one form of it, called proBDNF, is cut by certain enzymes into a new form called mature BDNF. It is in this form that it has its beneficial effect on neuron growth. Unfortunately, in its earlier form it is toxic to neurons.
This imbalance in the proportions of mature BDNF and proBDNF also appears to occur as we age, and in depression. It may also be a risk factor in Parkinson's and Huntington's diseases.
However, these findings suggest a new therapeutic approach.
In which context, it is interesting to note another new study, which has been busy analyzing the effects on brain cells of 2000 compounds, both natural and synthetic. Of the 256 that looked to have protective effects, nine were related to epicatechin, which is found in cocoa and green tea leaves.
While we’ve been aware for some time of these positive qualities, the study specifically identified epicatechin and epigallocatechin gallate (EGCG) as being the most effective at helping protect neurons by inducing production of BDNF.
One of the big advantages these compounds have is in their ability to cross the blood-brain barrier, making them a good candidate for therapy.
While green tea, dark chocolate, and cocoa are particularly good sources, many fruits also have good levels, in particular, black grapes, blackberries, apples, cherries, pears, and raspberries. (see this University of Davis document (pdf) for more detail)
 Bachis, A., Avdoshina V., Zecca L., Parsadanian M., & Mocchetti I.
(2012). Human Immunodeficiency Virus Type 1 Alters Brain-Derived Neurotrophic Factor Processing in Neurons.
The Journal of Neuroscience. 32(28), 9477 - 9484.
 Nath, S., Bachani M., Harshavardhana D., & Steiner J. P.
(2012). Catechins protect neurons against mitochondrial toxins and HIV proteins via activation of the BDNF pathway.
Journal of NeuroVirology.
First study: http://www.eurekalert.org/pub_releases/2012-07/gumc-pco070612.php
Second study: http://www.eurekalert.org/pub_releases/2012-08/s-hfp081412.php
Daily consumption of a high level of cocoa was found to improve cognitive scores, insulin resistance and blood pressure, in older adults with mild cognitive impairment.
Back in 2009, I reported briefly on a large Norwegian study that found that older adults who consumed chocolate, wine, and tea performed significantly better on cognitive tests. The association was assumed to be linked to the flavanols in these products. A new study confirms this finding, and extends it to older adults with mild cognitive impairment.
The study involved 90 older adults with MCI, who consumed either 990 milligrams, 520 mg, or 45 mg of a dairy-based cocoa drink daily for eight weeks. Their diet was restricted to eliminate other sources of flavanols (such as tea, red wine, apples and grapes).
Cognitive assessment at the end of this period revealed that, although scores on the MMSE were similar across all groups, those consuming higher levels of flavanol cocoa took significantly less time to complete Trail Making Tests A and B, and scored significantly higher on the verbal fluency test. Insulin resistance and blood pressure was also lower.
Those with the highest levels of flavanols did better than those on intermediate levels on the cognitive tests. Both did better than those on the lowest levels.
Changes in insulin resistance explained part, but not all, of the cognitive improvement.
One caveat: the group were generally in good health without known cardiovascular disease — thus, not completely representative of all those with MCI.
 Desideri, G., Kwik-Uribe C., Grassi D., Necozione S., Ghiadoni L., Mastroiacovo D., et al.
(2012). Benefits in Cognitive Function, Blood Pressure, and Insulin Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild Cognitive ImpairmentNovelty and Significance The Cocoa, Cognition, and Aging (CoCoA) Study.
Hypertension. 60(3), 794 - 801.
A mouse study provides more support for the value of exercise in preventing Alzheimer’s disease, and shows one of the ways in which it does so.
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.
 Maesako, M., Uemura K., Kubota M., Kuzuya A., Sasaki K., Hayashida N., et al.
(2012). Exercise Is More Effective than Diet Control in Preventing High Fat Diet-induced β-Amyloid Deposition and Memory Deficit in Amyloid Precursor Protein Transgenic Mice.
Journal of Biological Chemistry. 287(27), 23024 - 23033.
A rat study shows how high-fructose corn syrup hurts memory, and that omega-3 oils can counteract the effect.
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.
 Agrawal, R., & Gómez-Pinilla F.
(2012). ‘Metabolic Syndrome' in the Brain: Deficiency in Omega-3 Fatty Acid Exacerbates Dysfunctions in Insulin Receptor Signalling and Cognition.
The Journal of Physiology. 590(10), 2485 - 2499.
A large four-year study of older women has found high amounts of saturated fat were associated with greater cognitive decline, while higher amounts of monounsaturated fat were associated with better performance.
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.
 Okereke, O. I., Rosner B. A., Kim D. H., Kang J. H., Cook N. R., Manson JA. E., et al.
(2012). Dietary fat types and 4‐year cognitive change in community‐dwelling older women.
Annals of Neurology.
Two animal studies add to our understanding of why calorie restriction might help prevent cognitive impairment and dementia and how to accrue cognitive benefits from it. A human study adds to the evidence for the benefits of eating less.
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.
 Fusco, S., Ripoli C., Podda M V., Ranieri S C., Leone L., Toietta G., et al.
(2012). A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction.
Proceedings of the National Academy of Sciences. 109(2), 621 - 626.
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.
http://www.eurekalert.org/pub_releases/2011-12/cuor-elk121611.php http://www.guardian.co.uk/society/2012/feb/18/fasting-protect-brain-dise... http://www.scientificamerican.com/article.cfm?id=overeating-memory-loss
The study involved 104 healthy older adults (average age 87) participating in the Oregon Brain Aging Study. Analysis of the nutrient biomarkers in their blood revealed that those with diets high in omega 3 fatty acids and in vitamins C, D, E and the B vitamins had higher scores on cognitive tests than people with diets low in those nutrients, while those with diets high in trans fats were more likely to score more poorly on cognitive tests.
These were dose-dependent, with each standard deviation increase in the vitamin BCDE score ssociated with a 0.28 SD increase in global cognitive score, and each SD increase in the trans fat score associated with a 0.30 SD decrease in global cognitive score.
Trans fats are primarily found in packaged, fast, fried and frozen food, baked goods and margarine spreads.
Brain scans of 42 of the participants found that those with diets high in vitamins BCDE and omega 3 fatty acids were also less likely to have the brain shrinkage associated with Alzheimer's, while those with high trans fats were more likely to show such brain atrophy.
Those with higher omega-3 scores also had fewer white matter hyperintensities. However, this association became weaker once depression and hypertension were taken into account.
Overall, the participants had good nutritional status, but 7% were deficient in vitamin B12 (I’m surprised it’s so low, but bear in mind that these are already a select group, being healthy at such an advanced age) and 25% were deficient in vitamin D.
The nutrient biomarkers accounted for 17% of the variation in cognitive performance, while age, education, APOE genotype (presence or absence of the ‘Alzheimer’s gene’), depression and high blood pressure together accounted for 46%. Diet was more important for brain atrophy: here, the nutrient biomarkers accounted for 37% of the variation, while the other factors accounted for 40% (meaning that diet was nearly as important as all these other factors combined!).
The findings add to the growing evidence that diet has a significant role in determining whether or not, and when, you develop Alzheimer’s disease.
 Bowman, G. l, Silbert L. c, Howieson D., Dodge H. H., Traber M. g, Frei B., et al.
(2012). Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging.
Neurology. 78(4), 241 - 249.
Why is diabetes associated with cognitive impairment and even dementia in older adults? New research pinpoints two molecules that trigger a cascade of events that end in poor blood flow and brain atrophy.
The study involved 147 older adults (average age 65), of whom 71 had type 2 diabetes and had been taking medication to manage it for at least five years. Brain scans showed that the diabetic patients had greater blood vessel constriction than the age- and sex-matched controls, and more brain atrophy. The reduction in brain tissue was most marked in the grey matter in the parietal and occipital lobes and cerebellum. Research has found that, at this age, while the average brain shrinks by about 1% annually, a diabetic brain might shrink by as much as 15%. Diabetics also had more white matter hyperintensities in the temporal, parietal and occipital lobes.
Behaviorally, the diabetics also had greater depression, slower walking, and executive dysfunction.
The reduced performance of blood vessels (greater vasoconstriction, blunted vasodilatation), and increased brain atrophy in the frontal, temporal, and parietal lobes, was associated with two adhesion molecules – sVCAM and sICAM. White matter hyperintensities were not associated with the adhesion molecules, inflammatory markers, or blood vessel changes.
It seems that the release of these molecules, probably brought about by chronic hyperglycemia and insulin resistance, produces chronic inflammation, which in turn brings about constricted blood vessels, reduced blood flow, and finally loss of neurons. The blood vessel constriction and the brain atrophy were also linked to higher glucose levels.
The findings suggest that these adhesion molecules provide two biomarkers of vascular health that could enable clinicians to recognize impending brain damage, that could then perhaps be prevented.
The findings also add weight to the growing evidence that diabetes management is crucial in preventing cognitive decline.
 Novak, V., Zhao P., Manor B., Sejdić E., Alsop D., Abduljalil A., et al.
(2011). Adhesion Molecules, Altered Vasoreactivity, and Brain Atrophy in Type 2 Diabetes.
Diabetes Care. 34(11), 2438 - 2441.
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