neurogenesis

Preventing dementia: Diet & exercise

It's increasingly clear that eating a healthy diet can have a big impact on whether or not you develop dementia.

A study1 of nearly 2000 older adults has found that eating a Mediterranean diet was associated with less risk of developing mild cognitive impairment or of transitioning from MCI to Alzheimer's disease. The third with the highest scores for Mediterranean diet adherence had a 28% lower risk of developing MCI compared to the third with the lowest scores, and of those who already had MCI, those with the highest scores for Mediterranean diet adherence had a 48% less chance of developing Alzheimer’s.

Another, similar-sized study2, has found that those who adhered more strongly to a Mediterranean-type diet had a 40% risk reduction, and those who were very physically active had a 33% risk reduction of Alzheimer's -- doing both gave people a 60% reduction.

A Mediterranean-type diet is typically characterized by high intake of fish, vegetables, legumes, fruits, cereals and monounsaturated fatty acids; relatively low intake of dairy products, meats and saturated fats; and moderate alcohol consumption. Most of these components have been independently associated with reduced dementia risk. Let's look at them one by one.

Fruit & vegetables

A very large study3 of older adults found that those who ate fruits and vegetables daily reduced their risk of dementia by 30% compared to those who didn’t regularly eat fruits and vegetables. Another large, long-running epidemiological study4 found that those who drank three or more servings of fruit and vegetable juices per week had a 76% lower risk of developing Alzheimer’s disease than those who drank juice less than once a week. The benefit seemed greatest for those who carried the so-called “Alzheimer’s gene”.

This may not have anything to do with vitamin C. A five-year study5 involving nearly 3000 people has found that use of Vitamin C or E or both was not associated with a reduced risk of developing dementia or Alzheimer’s. However a study6 involving 4,740 elderly found the greatest reduction in both prevalence and incidence of Alzheimer's in those who used individual vitamin E and C supplements in combination. There was no significant benefit in these vitamins alone.

Of course, it is now well understood that taking vitamins as supplements is not the same as receiving them in food.

Two studies have come out in favor of a diet rich in foods containing vitamin E to help protect against Alzheimer's disease. One study7 involved 815 Chicago residents age 65 and older with no initial symptoms of mental decline, who were questioned about their eating habits and followed for an average of about four years. When factors like age and education were taken into account, those eating the most vitamin E-rich foods had a lower risk of developing Alzheimer’s, provided they did not have the ApoE e4 allele. This was not true when vitamin E was taken as a supplement. The effect of vitamin C was not statistically significant.

The other study8 involved 5,395 people in the Netherlands age 55 and older who were followed for an average of six years. Those with high intakes of vitamins E and C were less likely to become afflicted with Alzheimer's, regardless of whether they had the gene variation. This association was most pronounced for current smokers.

So beneficial effects of these vitamins may depend on genetics, smoking history, and possibly other lifestyle factors. But there are other valuable compounds common in fruits & vegetables. Another class of antioxidant chemicals, polyphenols, are now suspected. Polyphenols generally exist primarily in the skins of fruits and vegetables and are particularly abundant in teas, juices and wines.

A cell study9 also found that quercetin (a flavonoid with greater antioxidant and anticancer properties than vitamin C) protects against cellular damage. Quercetin is particularly abundant in apples (mainly in the skin, and especially the red ones). Other good sources are onions, blueberries and cranberries.

Another cell study10 found that compounds in blackcurrants (anthocyanins as well as polyphenols) strongly protect neuronal cells against the effects of amyloid-beta. Boysenberries contain the same compounds, and those that are darker are likely to be more potent.

The inconsistent findings regarding vitamins C and E may also have to do with the presence of folates. Data from the Baltimore Longitudinal Study of Aging11 revealed that although those with higher intake of folates, vitamin E and vitamin B6 had a lower risk of developing Alzheimer’s, statistical analysis showed it was only folate consumption that was significant. Those who had at least 400mcg of folates a day (the recommended daily allowance) had a 55% reduction in risk of developing Alzheimer’s. Unfortunately, most people who reached that level did so by taking supplements, suggesting the difficulty of doing so through diet alone.

Folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk; however, they are often destroyed by cooking or processing.

The benefits of folates probably has to do with its effect on homocysteine. A mouse study12 indicates that increased levels of homocysteine are produced by low intake of folate and B vitamins, and impair cognition through microvascular changes. 

High levels of homocysteine are associated not only with deficiencies in vitamin B12 and folate, but also with smoking.

High levels of homocysteine were associated in one study13 with a more than five-fold increase in the risk for stroke, a nearly five-fold risk for vascular dementia, and almost triple the risk for Alzheimer's disease. Findings from the long-running Framingham study14 found people with elevated levels of homocysteine in the blood had nearly double the risk of later developing Alzheimer’s disease.

Moreover, evidence from a study15 using genetically engineered mice suggests that increased levels of homocysteine in the brain cause damage to nerve cells in the hippocampus -- which can be repaired when there is an adequate amount of folate, but not when there is a deficiency.
 

Omega-3 oils & fish

One of the clearest findings in this area has been the benefits of regularly consuming omega-3 oils, fish oil, and fish. Several epidemiological studies have indicated that regularly eating fish (at least once a week) reduces risk of dementia. More recently, two very large studies have come out in support. One very large study3 of older adults found that those who regularly consumed omega-3 rich oils, such as canola oil, flaxseed oil and walnut oil, reduced their risk of dementia by 60% compared to people who did not regularly consume such oils. Additionally, those who ate fish at least once a week had a 40% lower risk of dementia -- but only if they did not carry ApoE4 gene.

Moreover, for those who didn’t have the gene, regular use of omega-6 rich oils, but not omega-3 rich oils or fish, were twice as likely to develop dementia compared to those who didn’t eat omega-6 rich oils (e.g., sunflower or grape seed oil).

The second study16 comes from the famous long-running Framingham Heart Study, which found that those with the highest levels of DHA (an omega-3 polyunsaturated fatty acid found in relatively high concentrations in cold-water fish) had a 47% lower risk of developing dementia. Those with these levels tended to eat an average three fish servings a week, as well as an average of .18 grams of DHA a day. Those at lower levels ate markedly less fish.

There is also some suggestion that omega-3 oils might help slow the progression of dementia. A Swedish study17 found that, although fatty acids DHA and EPA didn't slow cognitive decline in those with mild-to-moderate Alzheimer’s, they did slow decline in those with very mild cognitive impairment (a frequent precursor of dementia). It's been suggested that anti-inflammatory effects are an important reason for the benefit, why might explain why benefits only occur in the very early stages, when levels of inflammation seem to be higher.

Similar results were more recently reported18 from a large 18-month trial. This one, however, suggested that genetic status might be a factor -- that those without the “Alzheimer’s gene” ApoE4 might benefit even if impairment had progressed to mild-to-moderate Alzheimer’s.

There are a number of reasons why DHA might help brains.

A study involving genetically engineered mice19 has found that a diet high in DHA dramatically slowed the progression of Alzheimer's by cutting the harmful brain plaques that mark the disease. An earlier study20 showed that DHA protected against damage to the synaptic areas where brain cells communicate and enabled mice to perform better on memory tests. More recent research21 has revealed that DHA increases the production of LR11, a protein that is found at reduced levels in Alzheimer's patients and which is known to destroy the protein that forms the plaques associated with the disease.

Food sources of omega-3 fatty acids include fish such as salmon, halibut, mackerel and sardines, as well as almonds, walnuts, soy, flaxseed, and DHA-enriched eggs. These fish have high levels of DHA because they consume DHA-rich algae. Because these fishes' oiliness makes them absorb more mercury, dioxin, PCP and other metals, a less risky yet more costly strategy is to consume fish oil or purified DHA supplements made from algae.

Possible benefits of wine, tea, and coffee

There have been a number of reports that moderate alcohol consumption (generally defined as 1 drink or less per day for women and 1-2 drinks or less per day for men) may help reduce your risk of developing dementia, and a 2008 review of 44 studies22 supported this conclusion. 

However, given that alcohol has known negative effects on the brain, no one is recommending that non-drinkers take up the habit! All one can say is that there's no reason to alter your habits if you are a moderate drinker. On the other hand, if you drink more than this, you are probably best to knock it back to this level.

However, the evidence suggests that it is wine rather than alcohol in general that is beneficial for the brain. A large Danish study23 found that those who drank wine occasionally in the 1970s had a lower risk of developing dementia in the 1990s (when participants were 65 or older). However, occasional beer drinking was associated with an increased risk of developing dementia. But we cannot draw too hard & fast a conclusion from this, as eating habits were not investigated, and research suggests that wine drinkers may have better dietary habits than beer and liquor drinkers. Moreover, a very large study of older adults3, that found a significant effect of some dietary factors, found no effect of wine.

There are, however, some good reasons for believing regular drinking of red wine may help the aging brain. Red grapes contain several polyphenols that have been shown to significantly reduce cognitive deterioration in genetically engineered mice, by preventing the formation of amyloid beta. One of these is resveratrol; the others are catechin and epicatechin. Resveratrol was much vaunted when its effects were first discovered, but unfortunately it requires extremely high doses. The more recent discovery24 of the catechins is much more exciting, as they appear to be effective at much lower doses. The catechins are also abundant in tea and cocoa.

Tea, most particularly green tea, has also been found25 to inhibit the activity of enzymes associated with the development of Alzheimer's Disease. Green tea also obstructed the activity of beta-secretase.

These inhibitory properties were not found in coffee. However, a large, long-running Finnish study26 has found that those who were coffee drinkers at midlife had lower risk for dementia and Alzheimer’s later in life compared to those drinking no or only little coffee midlife. The lowest risk was found among moderate coffee drinkers (drinking 3-5 cups of coffee/day).

Restricting your calories

There has been some talk that calorie-restricted diets might help prevent Alzheimer's. So far, the only indications have come from experiments with genetically engineered mice. While there have been a number of studies providing evidence that high cholesterol, obesity, and other cardiovascular risk factors increase the likelihood of Alzheimer’s, it is decidedly premature to say whether calorie-restricted diets would benefit humans. Particularly since one of the early signs of Alzheimer's is weight loss. So it is certainly not recommended that people severely restrict their diets. More useful is removing certain food types (e.g., the "bad" oils; sugar -- there is some evidence that Alzheimer's may be a type of diabetes), and increasing consumption of others (fish, "good" oils, fruit & vegetables).

There may also be a genetic link. A four-year study27 of nearly 1000 older adults found that among those who carried the ApoE e4 gene, those who consumed the most calories had a 2.3 times greater chance of developing Alzheimer’s compared to those who ate the fewest calories. But calories weren't a factor for those without the gene.

Cholesterol

A study28 involving nearly 10,000 people who underwent health evaluations between 1964 and 1973 when they were between the ages of 40 and 45, has found that those with total cholesterol levels between 249 and 500 milligrams were one-and-a-half times more likely to develop Alzheimer's disease than those people with cholesterol levels of less than 198 milligrams. People with total cholesterol levels of 221 to 248 milligrams were more than one-and-a-quarter times more likely to develop Alzheimer's disease. High cholesterol increased risk regardless of midlife diabetes, high blood pressure, obesity, smoking and late-life stroke.

A review29 of autopsy cases of patients over 40 years old found that high blood cholesterol levels were correlated with the presence of amyloid deposits in the brain in the youngest subjects (aged 40-55).

An analysis30 of data on 1037 older women who had participated in a clinical trial of hormone replacement therapy found that high cholesterol levels increase the risk of cognitive impairment.

A large-scale Finnish study31 following 1449 men and women over 21 years found that raised systolic blood pressure and high serum cholesterol concentration, particularly in combination, in midlife, increase the risk of Alzheimer's disease in later life. Raised diastolic blood pressure had no significant effect.

However, the long-running, large-scale Framingham Heart study32 found that, after adjustment for age, sex, APOE genotype, smoking, body mass index, coronary heart disease, and diabetes, there was no significant association between AD risk and cholesterol level.

Previous studies suggesting that fat may be involved in the development of dementia and Alzheimer’s disease have been contradicted by a new study33 involving over 5,000 elderly people over a period of six years. The study found no correlation between fat and cholesterol intake and risk of dementia, and no evidence for a reduction in risk for those taking cholesterol lowering medication.

A cell study34 provides more understanding of why there might be a link between cholesterol and Alzheimer's disease. The study found that proteins which help control cholesterol levels in arterial walls were also present in neurons, and when the genes for these proteins were over-expressed, production of amyloid beta protein fell. The finding suggests a new approach to slowing Alzheimer’s. The study also showed that the apoE protein is extremely good at regulating cholesterol removal from neurons — the gene for this protein is a well-known genetic risk factor for Alzheimer's.

Diabetes

A large Swedish study35 has found that men with low insulin secretion capacity at age 50 were nearly one-and-a-half times more likely to develop Alzheimer’s disease than men without insulin problems. The risk was strongest in those who didn't have the APOE4 gene. Another large study36 found that diabetes was related to a significantly higher risk of developing amnestic mild cognitive impairment in older seniors (average age 76), after controlling for other risk factors. And a large study37 of post-menopausal women (mean age 67 years) found that those with poor blood sugar control were four times more likely to develop MCI or dementia. Findings38 from the long-running Religious Orders Study also support a link between diabetes and an increased risk of developing Alzheimer's disease.

Evidence from a mouse study39 suggests that diabetes might increase risk because elevated blood glucose levels interact with beta amyloid in a way damaging to blood vessels in the brain.
In fact it has been suggested that Alzheimer’s could be considered a third form of diabetes. Another study40 provides evidence that amyloid oligomers remove insulin receptors from nerve cells, rendering those neurons insulin resistant. Another mouse study41 suggests that low levels of insulysin, an enzyme that degrades insulin, are a factor. The enzyme, it seems, also degrades amyloid-beta peptides, and even a partial decrease in insulysin activity was found to raise amyloid-beta peptide levels in the brain.

Obesity

A review42 of 10 international studies published since 1995, covering just over 37,000 people, has found that obesity increased the relative risk of dementia by an average of 42% compared with normal weight. Being underweight increased the risk by 36%. For Alzheimer's Disease and vascular dementia, specifically, obesity was an even more significant risk: 80% and 73%, respectively. With regards to Alzheimer’s, obesity was more likely to be a risk factor for women, but men were more affected when it came to vascular dementia.

A very large study43 that measured abdominal fat at age 40 to 45 and dementia occurrence some 36 years later, found that those with the highest amount of abdominal fat were nearly three times more likely to develop dementia than those with the lowest amount of abdominal fat. Having a large abdomen increased the risk of dementia regardless of overall weight and existing health conditions, although being obese as well did increase the risk. Those more likely to have abdominal obesity, were women, non-whites, smokers, people with high blood pressure, high cholesterol or diabetes, and those with less than a high school level of education. And another large study44 found that those who at 40 were obese, or had high blood pressure, or high cholesterol levels, were twice as more likely to develop dementia by the age of 60. Having all three of these risk factors increased their chances six-fold.

And just to be really scary, when45 genetically engineered mice were fed a diet rich in fat, sugar and cholesterol for a mere nine months (although that is, of course, much longer for a mouse than it is for us!), they developed a preliminary stage of Alzheimer's pathology in their brains, suggesting that a ‘fast food’ diet could be a contributory factor in those with the Alzheimer’s gene.

Physical exercise & fitness

A number of studies have found that physical fitness reduces the risk of dementia. One way physical exercise can help fight dementia is through its ability to grow neurons in the hippocampus. This is well-established in rodent studies, and has been confirmed in small human studies. One such study46 found the association between physical fitness and hippocampus size was specifically associated with performance on certain spatial memory tests.  Another47 found that those with early Alzheimer's disease who were less physically fit had four times more brain shrinkage when compared to normal older adults than those who were more physically fit, suggesting the value of physical fitness extends to slowing down the progression of the disease.

Another reason for exercise to prevent dementia is through its effect on cardiovascular fitness, and a reasonably large four-year study48 did indeed find that the most active (top third) were significantly less likely to develop vascular dementia than the least active (bottom third). Interestingly, no such association was found with Alzheimer’s disease. However, at least two large studies have found a significantly reduced risk of dementia in those who had higher levels of fitness49 or exercised three or more times a week50. It may be that exercise has a greater effect on vascular dementia, but many cases of Alzheimer's dementia are actually mixed dementia, with a vascular component.

References: 
  1. Scarmeas, N. et al. 2009. Mediterranean Diet and Mild Cognitive Impairment. Archives of Neurology, 66(2), 216-225.
  2. Scarmeas, N. et al. 2009. Physical Activity, Diet, and Risk of Alzheimer Disease. Journal of the American Medical Association, 302(6), 627-637.
  3. Barberger-Gateau, P. et al. 2007. Dietary patterns and risk of dementia: The Three-City cohort study. Neurology, 69, 1921-1930.
  4. Dai, Q. et al. 2006. Fruit and Vegetable Juices and Alzheimer's Disease: The Kame Project. The American Journal of Medicine, 119 (9), 751-759
  5. Gray, S.L. et al. 2008. Antioxidant Vitamin Supplement Use and Risk of Dementia or Alzheimer's Disease in Older Adults. Journal of the American Geriatrics Society, 56 (2), 291–295.
  6. Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V., Gustafson, D., Tschanz, J.T., Norton, M.C., Welsh-Bohmer, K.A. & Breitner, J.C.S. 2004. Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study. Archives of Neurology, 61, 82-88.
  7. Engelhart, M.J., Geerlings, M.I., Ruitenberg, A., van Swieten, J.C., Hofman, A., Witteman, J.C.M. & Breteler, M.M.B. 2002. Dietary Intake of Antioxidants and Risk of Alzheimer Disease. JAMA, 287, 3223-3229.
  8. Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, D.A., Aggarwal, N., Wilson, R.S. & Scherr, P.A. 2002. Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study. JAMA, 287, 3230-3237.
  9. Heo, H.J. & Lee, C.Y. 2004. Protective Effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration. Journal of Agricultural and Food Chemistry, 52 (25), 7514–7517.
  10. Ghosh, D., McGhie, T.K., Zhang, J., Adaim, A. & Skinner, M. 2006. Effects of anthocyanins and other phenolics of boysenberry and blackcurrant as inhibitors of oxidative stress and damage to cellular DNA in SH-SY5Y and HL-60 cells. Journal of the Science of Food and Agriculture, in press.
  11. Corrada, M.M., Kawas,C.H., Hallfrisch,J., Muller,D. & Brookmeyer,R. Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore Longitudinal Study of Aging. Alzheimer’s & Dementia, 1 (1), 11-18.
  12. Troen, A.M. et al. 2008. B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice. Proceedings of the National Academy of Sciences, 105, 12474-12479.
  13. McIlroy, S.P., Dynan, K.B., Lawson, J.T., Patterson, C.C. & Passmore, A.P. 2002. Moderately Elevated Plasma Homocysteine, Methylenetetrahydrofolate Reductase Genotype, and Risk for Stroke, Vascular Dementia, and Alzheimer Disease in Northern Ireland. Stroke, 33, 2351–2356.
  14. Seshadri, S., Beiser, A., Selhub, J., Jacques, P.F., Rosenberg, I.H., D'Agostino, R.B., Wilson, P.W.F. & Wolf, P.A. 2002. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. The New England Journal of Medicine, 346, 476-483.
  15. Kruman, I.I., Kumaravel, T.S., Lohani, A., Pedersen, W.A., Cutler, R.G., Kruman, Y., Haughey, N., Lee, J., Evans, M. & Mattson, M.P. 2002. Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's Disease. Journal of Neuroscience, 22, 1752-1762.
  16. Schaefer, E.J. et al. 2006. Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease. Archives of Neurology, 63, 1545-1550.
  17. Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.
  18. Quinn, J.F. et al. 2009. A clinical trial of docosahexaenoic acid (DHA) for the treatment of Alzheimer's disease. Presented at the Alzheimer's Association International Conference on Alzheimer's Disease July 11-16 in Vienna.
    Yurko-Mauro, K. et al. 2009. Results of the MIDAS Trial: Effects of Docosahexaenoic Acid on Physiological and Safety Parameters in Age-Related Cognitive Decline. Presented at the Alzheimer's Association International Conference on Alzheimer's Disease July 11-16 in Vienna.
  19. Lim, G.P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O., Salem, N.Jr, Frautschy, S.A. & Cole, G.M. 2005. A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model. Journal of Neuroscience, 25(12), 3032-3040.
  20. Calon, F. et al. 2004. Docosahexaenoic Acid Protects from Dendritic Pathology in an Alzheimer's Disease Mouse Model. Neuron, 43 (5), 633-645.
  21. Ma, Q-L. et al. 2007. Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention. Journal of Neuroscience, 27 (52), 14299 - 14307.
  22. Collins, M.A. et al. 2008. Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic Studies. Alcoholism: Clinical and Experimental Research, Published Online 20 November.
  23. Truelsen, T., Thudium, D. & Grønbæk, M. 2002. Amount and type of alcohol and risk of dementia: The Copenhagen City Heart Study. Neurology, 59, 1313-1319.
  24. Wang, J. et al. 2008. Grape-Derived Polyphenolics Prevent Aβ Oligomerization and Attenuate Cognitive Deterioration in a Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 28, 6388-6392.
  25. Okello, E.J., Savelev, S.U. & Perry, E.K. 2004. In vitro Anti-beta-secretase and dual anti-cholinesterase activities of Camellia sinensis L. (tea) relevant to treatment of dementia. Phytotherapy Research, 18 (8), 624-627.
  26. Eskelinen, M.H. et al. 2009. Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-based CAIDE Study. Journal of Alzheimer's Disease, 16(1).
  27. Luchsinger, J.A. et al. 2002. Caloric Intake and the Risk of Alzheimer Disease. Archives of Neurology, 59 (8), 1258-1263.
  28. Solomon, A. et al. 2008. Midlife Serum Total Cholesterol and Risk of Alzheimers Disease and Vascular Dementia Three Decades Later. Presented at the American Academy of Neurology Annual Meeting in Chicago, April 16. Abstract
  29. Pappolla, M.A. et al. 2003. Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology, 61, 199-205.
  30. Yaffe, K., Barrett-Connor, E., Lin, F. & Grady, D. 2002. Serum Lipoprotein Levels, Statin Use, and Cognitive Function in Older Women. Archives of Neurology, 59,378-384.
  31. Kivipelto, M., Helkala, E., Laakso, M. P., Hanninen, T., Hallikainen, M., Alhainen, K., Soininen, H., et al. (2001). Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ, 322(7300), 1447-1451.  http://www.bmj.com/cgi/content/full/322/7300/1447
  32. Tan, Z.S., Seshadri, S., Beiser, A., Wilson, P.W.F., Kiel, D.P., Tocco, M., D'Agostino, R.B. & Wolf, P.A. 2003. Plasma Total Cholesterol Level as a Risk Factor for Alzheimer Disease: The Framingham Study. Archives of Internal Medicine, 163, 1053-1057.
  33. Engelhart, M.J., Geerlings, M.I., Ruitenberg, A., van Swieten, J.C., Hofman, A., Witteman, J.C.M. & Breteler, M.M.B. 2002. Diet and risk of dementia: Does fat matter?: The Rotterdam Study. Neurology, 59, 1915-1921.
  34. Kim, W.S. et al. 2007. Role of ABCG1 and ABCA1 in Regulation of Neuronal Cholesterol Efflux to Apolipoprotein E Discs and Suppression of Amyloid-β Peptide Generation. Journal of Biological Chemistry, 282, 2851-2861.
  35. Rönnemaa, E. et al. 2008. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology, first published on April 9 as doi: doi:10.1212/01.wnl.0000310646.32212.3a
  36. Luchsinger, J.A. et al. 2007. Relation of Diabetes to Mild Cognitive Impairment. Archives of Neurology, 64, 570-575.
  37. Yaffe, K. et al. 2006. Glycosylated Hemoglobin Level and Development of Mild Cognitive Impairment or Dementia in Older Women. Journal of Nutrition, Health, and Aging, 10 (4).
  38. Arvanitakis, Z., Wilson, R.S., Bienias, J.L., Evans, D.A. & Bennett, D.A. 2004. Diabetes Mellitus and Risk of Alzheimer Disease and Decline in Cognitive Function. Archives of Neurology, 61, 661-666.
  39. Burdo, J.R. et al. 2008. The pathological interaction between diabetes and presymptomatic Alzheimer's disease. Neurobiology of Aging, Available online 26 March 2008 .
  40. Zhao,W-Q. et al. 2007. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB Journal, published online ahead of print August 24.
  41. Miller, B.C., Eckman, E.A., Sambamurti, K., Dobbs, N., Chow, K.M., Eckman, C.B., Hersh, L.B. & Thiele, D.L. 2003. Amyloid-β peptide levels in brain are inversely correlated with insulysin activity levels in vivo. PNAS, 100, 6221-6226. published online before print.
  42. Beydoun, M.A., Beydoun, H.A. & Wang, Y. 2008. Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obesity Reviews, 9 (3), 204–218.
  43. Whitmer, R.A., et al. 2008. Central obesity and increased risk of dementia more than three decades later. Neurology, published online ahead of print March 26.
  44. Kivipelto,M. et al. 2006. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurology, advance online publication 3 August
  45. Akterin, S. 2008. From cholesterol to oxidative stress in Alzheimer's disease: A wide perspective on a multifactorial disease. Doctoral thesis, Karolinska Institutet. http://diss.kib.ki.se/2008/978-91-7409-172-4/
  46. Erickson, K.I. et al.  2009. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus, Published online 2 January.
  47. Burns, J.M. et al. 2008. Cardiorespiratory fitness and brain atrophy in early Alzheimer disease. Neurology, 71, 210-216.
  48. Ravaglia, G. et al. 2007. Physical activity and dementia risk in the elderly. Findings from a prospective Italian study. Neurology, published online ahead of print December 19.
  49. Wang, L., Larson, E.B., Bowen, J.D. & van Belle, G. 2006. Performance-Based Physical Function and Future Dementia in Older People. Archives of Internal Medicine, 166, 1115-1120.
  50. Larson, E.B., Wang, L., Bowen, J.D., McCormick, W.C., Teri, L., Crane, P., & Kukull, W. 2006. Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older. Annals of Internal Medicine, 144 (2), 73-81.

Adult Neurogenesis

Neurogenesis occurs in two main areas in the adult brain: the hippocampus and the olfactory bulb.

The transformation of a new cell into a neuron appears to crucially involve a specific protein called WnT3, that's released by support cells called astrocytes.

A chemical called BDNF also appears critical for the transformation into neurons.

Most recently, T-cells have also been revealed as important for neurogenesis to occur.

The extent and speed of neurogenesis can also be enhanced by various chemicals. Nerve growth factors appear to enhance the proliferation of precursor cells (cells with the potential to become neurons), and the prion protein that, damaged, causes mad cow disease, appears in its normal state to speed the rate of neurogenesis.

The integration of the new neuron into existing networks appears to need a brain chemical called GABA.

Indications are that moderate alcohol may enhance neurogenesis, but excess alcohol certainly has a negative effect. Most illegal drugs have a negative effect, but there is some suggestion cannabinoids may enhance neurogenesis. Antidepressants also seem to have a positive effect, while stress and anxiety reduce neurogenesis. However, positive social experiences, such as being of high status, can increase neurogenesis. Physical activity, mental stimulation, and learning, have all been shown to have a positive effect on neurogenesis.

What is neurogenesis?

Neurogenesis — the creation of new brain cells — occurs of course at a great rate in the very young. For a long time, it was not thought to occur in adult brains — once you were grown, it was thought, all you could do was watch your brain cells die!

Adult neurogenesis (the creation of new brain cells in adult brains) was first discovered in 1965, but only recently has it been accepted as a general phenomenon that occurs in many species, including humans (1998).

Where does adult neurogenesis occur?

It's now widely accepted that adult neurogenesis occurs in the subgranular zone of the dentate gyrus within the hippocampus and the subventricular zone (SVZ) lining the walls of the lateral ventricles within the forebrain. It occurs, indeed, at a quite frantic rate — some 9000 new cells are born in the dentate gyrus every day in young adult rat brains — but under normal circumstances, at least half of those new cells will die within one or two months.

The neurons produced in the SVZ are sent to the olfactory bulb, while those produced in the dentate gyrus are intended for the hippocampus.

Adult neurogenesis might occur in other regions, but this is not yet well-established. However, recent research has found that small, non-pyramidal, inhibitory interneurons are being created in the cortex and striatum. These new interneurons appear to arise from a previously unknown class of local precursor cells. These interneurons make and secrete GABA (see below for why GABA is important), and are thought to play a role in regulating larger types of neurons that make long-distance connections between brain regions.

How does neurogenesis occur?

New neurons are spawned from the division of neural precursor cells — cells that have the potential to become neurons or support cells. How do they decide whether to remain a stem cell, turn into a neuron, or a support cell (an astrocyte or oligodendrocyte)?

Observation that neuroblasts traveled to the olfactory bulb from the SVZ through tubes formed by astrocytes has led to an interest in the role of those support cells. It's now been found that astrocytes encourage both precursor cell proliferation and their maturation into neurons — precursor cells grown on glia divide about twice as fast as they do when grown on fibroblasts, and are about six times more likely to become neurons.

Adult astrocytes are only about half as effective as embryonic astrocytes in promoting neurogenesis.

It’s been suggested that the role of astrocytes may help explain why neurogenesis only occurs in certain parts of the brain — it may be that there’s something missing from the glial cells in those regions.

The latest research suggests that the astrocytes influence the decision through a protein that it secretes called Wnt3. When Wnt3 proteins were blocked in the brains of adult mice, neurogenesis decreased dramatically; when additional Wnt3 was introduced, neurogenesis increased.

How are these new neurons then integrated into existing networks? Mouse experiments have found that the brain chemical called GABA is critical. Normally, GABA inhibits neuronal signals, but it turns out that with new neurons, GABA has a different effect: it excites them, and prepares them for integration into the adult brain. Thus a constant flood of GABA is needed initially; the flood then shifts to a more targeted pulse that gives the new neuron specific connections that communicate using GABA; finally, the neuron receives connections that communicate via another chemical, glutamate. The neuron is now ready to function as an adult neuron, and will respond to glutamate and GABA as it should.

The creation and development of new neurons in the adult brain is very much a "hot" topic right now — it's still very much a work-in-progress. However, it is clear that other brain chemicals are also involved. An important one is BDNF (brain-derived neurotrophic factor), which seems to be needed during the proliferation of hippocampal precursor cells to trigger their transformation into neurons.

Other growth factors have been found to stimulate proliferation of hippocampal progenitor cells: FGF-2 (fibroblast growth factor-2) and EGF (epidermal growth factor).

Recently it has been discovered that the normal form of the prion protein which, when malformed, causes mad cow disease, is also involved in neurogenesis. These proteins, in their normal form, are found throughout our bodies, and particularly in our brains. Now it seems that the more of these prion proteins that are available, the faster neural precursor cells turn into neurons.

The immune system's T cells (which recognize brain proteins) are also critically involved in enabling neurogenesis to occur. Among mice given environmental enrichment, only those with healthy T-cells had their production of new neurons boosted.

Factors that influence neurogenesis

A number of factors have been found to affect the creation and survival of new neurons. For a start, damage to the brain (from a variety of causes) can provoke neurogenesis.

Moderate alcohol consumption over a relatively long period of time can also enhance the formation of new nerve cells in the adult brain (this may be related to alcohol's enhancement of GABA's function). Excess alcohol, however, has a detrimental effect on the formation of new neurons in the adult hippocampus. But although neurogenesis is inhibited during alcohol dependency, it does recover. A pronounced increase in new neuron formation in the hippocampus was found within four-to-five weeks of abstinence. This included a twofold burst in brain cell proliferation at day seven of abstinence.

Most drugs of abuse such as nicotine, heroine, and cocaine suppress neurogenesis, but a new study suggests that cannabinoids also promote neurogenesis. The study involved a synthetic cannabinoid, which increased the proliferation of progenitor cells in the hippocampal dentate gyrus of mice, in a similar manner as some antidepressants have been shown to do. The cannabinoid also produced similar antidepressant effects. Further research is needed to confirm this early finding.

If antidepressants promote neurogenesis, it won't be surprising to find that chronic stress, anxiety and depression are associated with losing hippocampal neurons. A rat study has also found that stress in early life can permanently impair neurogenesis in the hippocampus.

Showing the other side of this picture, perhaps, an intriguing rat study found that status affected neurogenesis in the hippocampus, with high-status animals having around 30% more neurons in their hippocampus after being placed in a naturalistic setting with other rats.

Also, a study into the brains of songbirds found that birds living in large groups have more new neurons and probably a better memory than those living alone.

Both physical activity and environmental enrichment (“mental stimulation”) have been shown to affect both how many cells are born in the dentate gyrus of rats and how many survive. Learning that uses the hippocampus has also been shown to have a positive effect, although results here have been inconsistent.

Inconsistent results from studies looking at neurogenesis are, it is suggested, largely because of a confusion between proliferation and survival. Neurogenesis is measured in terms of these two factors, which researchers often fail to distinguish between: the generation of new brain cells, and their survival. But these are separate factors, that are independently affected by various factors.

The inconsistency found in the effects of learning may also be partly explained by the complex nature of the effects. For example, during the later phase of learning, when performance is starting to plateau, neurons created during the late phase were more likely to survive, but neurons created during the early phase of more rapid learning disappeared. It’s speculated that that this may be a “pruning” process by which cells that haven’t made synaptic connections are removed from the network.

And finally, rodent studies suggest a calorie-restricted diet may also be of benefit.

It's not all about growing new neurons

A few years ago, we were surprised by news that new neurons could be created in the adult brain. However, it’s remained a tenet that adult neurons don’t grow — this because researchers have found no sign that any structural remodelling takes place in an adult brain. Now a mouse study using new techniques has revealed that dramatic restructuring occurs in the less-known, less-accessible inhibitory interneurons. Dendrites (the branched projections of a nerve cell that conducts electrical stimulation to the cell body) show sometimes dramatic growth, and this growth is tied to use, supporting the idea that the more we use our minds, the better they will be.

References: 
  1. Aberg, E., Hofstetter, C., Olson, L. & Brené, S. 2005. Moderate ethanol consumption increases hippocampal cell proliferation and neurogenesis in the adult mouse. International Journal of Neuropsychopharmacology, 8(4), 557-567.
  2. Bull, N.D. & Bartlett, P.F. 2005. The Adult Mouse Hippocampal Progenitor Is Neurogenic But Not a Stem Cell. Journal of Neuroscience, 25, 10815-10821.
  3. Dayer, A.G., Cleaver, K.M., Abouantoun, T. & Cameron, H.A. 2005. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. Journal of Cell Biology, 168, 415-427.
  4. Döbrössy, M.D., Drapeau, E., Aurousseau, C., Le Moal, M., Piazza, P.V. & Abrous, D.N. 2003. Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date. Molecular Psychiatry, 8, 974-982.
  5. Ge, S., Goh, E.L.K., Sailor, K.A., Kitabatake, Y., Ming, G-L. & Song, H. 2005. GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature advance online publication; published online 11 December 2005
  6. Hairston, I.S., Little, M.T.M., Scanlon, M.D., Barakat, M.T., Palmer, T.D., Sapolsky, R.M. & Heller, H.C. 2005. Sleep Restriction Suppresses Neurogenesis Induced by Hippocampus-Dependent Learning. Journal of Neurophysiology, 94 (6), 4224-4233.
  7. Jiang, W. et al. 2005. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Journal of Clinical Investigation, 115, 3104-3116.
  8. Johnson, R.A., Rhodes, J.S., Jeffrey, S.L., Garland, T. Jr., & Mitchell, G.S. 2003. Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience, 121(1), 1-7.
  9. Karten, Y.J.G., Olariu, A. & Cameron, H.A. 2005. Stress in early life inhibits neurogenesis in adulthood. Trends in Neurosciences, 28 (4), 171-172.
  10. Kozorovitskiy, Y. & Gould, E.J. 2004. Dominance Hierarchy Influences Adult Neurogenesis in the Dentate Gyrus. The Journal of Neuroscience,24(30), 6755-6759.
  11. Lee, J., Duan, W., Long, J.M., Ingram, D.K. & Mattson, M.P. 2000. Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. Journal of Molecular Neuroscience, 15(2), 99-108.
  12. Lie, D-C., Colamarino, S.A., Song, H-J., Désiré, L., Mira, H., Consiglio, A., Lein, E.S., Jessberger, S., Lansford, H., Dearie, A.R. & Gage, F.H. 2005. Wnt signalling regulates adult hippocampal neurogenesis. Nature, 437, 1370-1375.
  13. Lipkind, D., Nottebohm, F., Rado, R. & Barnea, A.2002. Social change affects the survival of new neurons in the forebrain of adult songbirds. Behavioural Brain Research, 133 (1), 31-43.
  14. Lombardino, A.J., Li, X-C., Hertel, M & Nottebohm, F. 2005. Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels. PNAS, 102(22), 8036-8041.
  15. Nixon, K. & Crews, F.T. 2004. Temporally Specific Burst in Cell Proliferation Increases Hippocampal Neurogenesis in Protracted Abstinence from Alcohol. Journal of Neuroscience, 24, 9714-9722.
  16. Prickaerts, J., Koopmans, G., Blokland, A. & Scheepens, A. 2004. Learning and adult neurogenesis: Survival with or without proliferation? Neurobiology of Learning and Memory, 81, 1-11.
  17. Santarelli, L. et al. 2003. Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants. Science, 301(5634), 805-809.
  18. Song, H., Stevens, C.F. & Gage, F.H. 2002. Astroglia induce neurogenesis from adult neural stem cells. Nature, 417, 39-44.
  19. Steele, A.D., Emsley, J.G., Özdinler, P.H., Lindquist, S. & Macklis, J.D. 2006. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. PNAS, 103, 3416-3421.
  20. Yoshimura, S. et al. 2003. FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice. Journal of Clinical Investigation, 112, 1202-1210.
  21. Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J. & Schwartz, M. 2006. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nature Neuroscience, 9, 268-275.

A little stress can make brains sharper

stock image lab rat

While it’s well-established that chronic stress has all sorts of harmful effects, including on memory and cognition, the judgment on brief bouts of acute stress has been more equivocal. There is a certain amount of evidence that brief amounts of stress can be stimulating rather than harmful, and perhaps even necessary if we are to reach our full potential.

Why learning gets harder as we get older

A mouse study shows that weakening unwanted or out-of-date connections is as important as making new connections, and that neurological changes as we age reduces our ability to weaken old connections.

A new study adds more support to the idea that the increasing difficulty in learning new information and skills that most of us experience as we age is not down to any difficulty in acquiring new information, but rests on the interference from all the old information.

Memory is about strengthening some connections and weakening others. A vital player in this process of synaptic plasticity is the NMDA receptor in the hippocampus. This glutamate receptor has two subunits (NR2A and NR2B), whose ratio changes as the brain develops. Children have higher ratios of NR2B, which lengthens the time neurons talk to each other, enabling them to make stronger connections, thus optimizing learning. After puberty, the ratio shifts, so there is more NR2A.

Of course, there are many other changes in the aging brain, so it’s been difficult to disentangle the effects of this changing ratio from other changes. This new study genetically modified mice to have more NR2A and less NR2B (reflecting the ratio typical of older humans), thus avoiding the other confounds.

To the researchers’ surprise, the mice were found to be still good at making strong connections (‘long-term potentiation’ - LTP), but instead had an impaired ability to weaken existing connections (‘long-term depression’ - LTD). This produces too much noise (bear in mind that each neuron averages 3,000 potential points of contact (i.e., synapses), and you will see the importance of turning down the noise!).

Interestingly, LTD responses were only abolished within a particular frequency range (3-5 Hz), and didn’t affect 1Hz-induced LTD (or 100Hz-induced LTP). Moreover, while the mice showed impaired long-term learning, their short-term memory was unaffected. The researchers suggest that these particular LTD responses are critical for ‘post-learning information sculpting’, which they suggest is a step (hitherto unknown) in the consolidation process. This step, they postulate, involves modifying the new information to fit in with existing networks of knowledge.

Previous work by these researchers has found that mice genetically modified to have an excess of NR2B became ‘super-learners’. Until now, the emphasis in learning and memory has always been on long-term potentiation, and the role (if any) of long-term depression has been much less clear. These results point to the importance of both these processes in sculpting learning and memory.

The findings also seem to fit in with the idea that a major cause of age-related cognitive decline is the failure to inhibit unwanted information, and confirm the importance of keeping your mind actively engaged and learning, because this ratio is also affected by experience.

Exercise may be best way to protect against brain shrinkage

A large study of older adults shows that physical exercise is associated with less brain atrophy and fewer white matter lesions. A small study shows that frail seniors benefit equally from exercise.

A study using data from the Lothian Birth Cohort (people born in Scotland in 1936) has analyzed brain scans of 638 participants when they were 73 years old. Comparing this data with participants’ earlier reports of their exercise and leisure activities at age 70, it was found that those who reported higher levels of regular physical activity showed significantly less brain atrophy than those who did minimal exercise. Participation in social and mentally stimulating activities, on the other hand, wasn’t associated with differences in brain atrophy.

Regular physical exercise was also associated with fewer white matter lesions. While leisure activity was also associated with healthier white matter, this was not significant after factors such as age, social class, and health status were taken into account.

Unfortunately, this study is reported in a journal to which I don’t have access. I would love to have more details about the leisure activities data and the brain scans. However, although the failure to find a positive effect of stimulating activities is disappointing, it’s worth noting another recent study, that produced two relevant findings. First, men with high levels of cognitive activity showed a significant reduction in white matter lesions, while women did not. Women with high levels of cognitive activity, on the other hand, showed less overall brain atrophy — but men did not.

Secondly, both genders showed less atrophy in a particular region of the prefrontal cortex, but there was no effect on the hippocampus — the natural place to look for effects (and the region where physical exercise is known to have positive effects).

In other words, the positive effects of cognitive activity on the brain might be quite different from the positive effects of physical exercise.

The findings do, of course, add to the now-compelling evidence for the benefits of regular physical activity in fighting cognitive decline.

It’s good news, then, that a small study has found that even frail seniors can derive significant benefits from exercise.

The study involved 83 older adults (61-89), some of whom were considered frail. Forty-three took part in group exercises (3 times a week for 12 weeks), while 40 were wait-listed controls. Participants were assessed for physical capacity, quality of life and cognitive health a week before the program began, and at the end.

Those who took part in the exercise program significantly improved their physical capacity, cognitive performance, and quality of life. These benefits were equivalent among frail and non-frail participants.

Frailty is associated with a higher risk of falls, hospitalizations, cognitive decline and psychological distress, and, of course, increases with age. In the U.S, it’s estimated that 7% of seniors aged 65 to 74, 18% of those aged 75 to 84, and 37% of seniors over the age of 85 are frail.

The value of intensive practice

Changing your brain - which is what happens when you learn, and when yoe encode new experiences, or have new thoughts - is crucial for keeping your brain 'young'.

Learning a new language may be especially beneficial for keeping your brain flexible and thus fighting age-related cognitive decline.

Intense periods of learning may be especially beneficial.

Let’s talk about the cognitive benefits of learning and using another language.

In a recent news report, I talked about the finding that intensive learning of a very novel language significantly grew several brain regions, of which two were positively associated with language proficiency. These regions were the right hippocampus and the left superior temporal gyrus. Growth of the first of these probably reflects the learning of a great many new words, and the second may reflect heavy use of the phonological loop (a part of working memory).

How green tea helps fight cognitive decline & dementia

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.

Importance of Vitamin C during pregnancy

A guinea pig study demonstrates that low levels of vitamin C during pregnancy have long-lasting effects on the child's hippocampus.

Like us, guinea pigs can’t make vitamin C, but must obtain it from their diet. This makes them a good model for examining the effects of vitamin C deficiency.

In a recent study looking specifically at the effects of prenatal vitamin C deficiency, 80 pregnant guinea pigs were fed a diet that was either high or low in vitamin C. Subsequently, 157 of the newborn pups were randomly allocated to either a low or high vitamin C diet (after weaning), creating four conditions: high/high (controls); high/low (postnatal depletion); low/high (postnatal repletion); low/low (pre/postnatal deficiency). Only males experienced the high/low condition (postnatal depletion).

Only the postnatal depletion group showed any effect on body weight; no group showed an effect on brain weight.

Nevertheless, although the brain as a whole grew normally, those who had experienced a prenatal vitamin C deficiency showed a significantly smaller hippocampus (about 10-15% smaller). This reduction was not reversed by later repletion.

This reduction appeared to be related to a significant reduction in the migration of new neurons into the dentate gyrus. There was no difference in the creation or survival of new neurons in the hippocampus.

This finding suggests that marginal deficiency in vitamin C during pregnancy (a not uncommon occurrence) may have long-term effects on offspring.

Learning another language boosts white matter

Foreign language learning increases the white matter in the language network and the bridge joining the hemispheres, perhaps helping explain why bilinguals have better executive control.

In my last report, I discussed a finding that intensive foreign language learning ‘grew’ the size of certain brain regions. This growth reflects gray matter increase. Another recent study looks at a different aspect: white matter.

In the study, monthly brain scans were taken of 27 college students, of whom 11 were taking an intensive nine-month Chinese language course. These brain scans were specifically aimed at tracking white matter changes in the students’ brains.

Significant changes were indeed observed in the brains of the language learners. To the researchers’ surprise, however, the biggest changes were observed in an area not previously considered part of the language network: the white matter tracts that cross the corpus callosum, the main bridge between the hemispheres. (I’m not quite sure why they were surprised, since a previous study had found that bilinguals showed higher white matter integrity in the corpus callosum.)

Significant changes were also observed within the left-hemisphere language network and in the right temporal lobe. The rate of increase in white matter was linear, showing a steady progression with each passing month.

The researchers suggest that plasticity in the adult brain may differ from that seen in children’s brains. While children’s brains change mainly through the pruning of unwanted connections and the death of unwanted cells, adult brains may rely mainly on neurogenesis and myelinogenesis.

The growth of new myelin is a process that is still largely mysterious, but it’s suggested that activity at the axons (the extensions of neurons that carry the electrical signals) might trigger increases in the size, density, or number of oligodendrocytes (the cells responsible for the myelin sheaths). This process is thought to be mediated by astrocytes, and in recent years we have begun to realize that astrocytes, long regarded as mere ‘support cells’, are in fact quite important for learning and memory. Just how important is something researchers are still working on.

The finding of changes between the frontal hemispheres and caudate nuclei is consistent with a previously-expressed idea that language learning requires the development of a network to control switching between languages.

Does the development of such a network enhance the task-switching facility in working memory? Previous research has found that bilinguals tend to have better executive control than monolinguals, and it has been suggested that the experience of managing two (or more) languages reorganizes certain brain networks, creating a more effective basis for executive control.

As in the previous study, the language studied was very different from the students’ native language, and they had no previous experience of it. The level of intensity was of course much less.

I do wonder if the fact that the language being studied was Mandarin Chinese limits the generality of these findings. Because of the pictorial nature of the written language, Chinese has been shown to involve a wider network of regions than European languages.

Nevertheless, the findings add to the evidence that adult brains retain the capacity to reorganize themselves, and add to growing evidence that we should be paying more attention to white matter changes.

Reference: 

[3143] Schlegel, A. A., Rudelson J. J., & Tse P. U. (2012).  White Matter Structure Changes as Adults Learn a Second Language. Journal of Cognitive Neuroscience. 24(8), 1664 - 1670.

Bialystok, E., Craik, F. I. M., & Luk, G. (2012). Bilingualism: consequences for mind and brain. Trends in Cognitive Sciences, 16(4), 240–250. doi:10.1016/j.tics.2012.03.001

Luk, G. et al. (2011) Lifelong bilingualism maintains white matter integrity in older adults. J. Neurosci. 31, 16808–16813

Growing the brain with a new language

A new study adds to the growing evidence for the cognitive benefits of learning a new language, and hints at why some people might be better at this than others.

A small Swedish brain imaging study adds to the evidence for the cognitive benefits of learning a new language by investigating the brain changes in students undergoing a highly intensive language course.

The study involved an unusual group: conscripts in the Swedish Armed Forces Interpreter Academy. These young people, selected for their talent for languages, undergo an intensive course to allow them to learn a completely novel language (Egyptian Arabic, Russian or Dari) fluently within ten months. This requires them to acquire new vocabulary at a rate of 300-500 words every week.

Brain scans were taken of 14 right-handed volunteers from this group (6 women; 8 men), and 17 controls that were matched for age, years of education, intelligence, and emotional stability. The controls were medical and cognitive science students. The scans were taken before the start of the course/semester, and three months later.

The brain scans revealed that the language students showed significantly greater changes in several specific regions. These regions included three areas in the left hemisphere: the dorsal middle frontal gyrus, the inferior frontal gyrus, and the superior temporal gyrus. These regions all grew significantly. There was also some, more selective and smaller, growth in the middle frontal gyrus and inferior frontal gyrus in the right hemisphere. The hippocampus also grew significantly more for the interpreters compared to the controls, and this effect was greater in the right hippocampus.

Among the interpreters, language proficiency was related to increases in the right hippocampus and left superior temporal gyrus. Increases in the left middle frontal gyrus were related to teacher ratings of effort — those who put in the greatest effort (regardless of result) showed the greatest increase in this area.

In other words, both learning, and the effort put into learning, had different effects on brain development.

The main point, however, is that language learning in particular is having this effect. Bear in mind that the medical and cognitive science students are also presumably putting in similar levels of effort into their studies, and yet no such significant brain growth was observed.

Of course, there is no denying that the level of intensity with which the interpreters are acquiring a new language is extremely unusual, and it cannot be ruled out that it is this intensity, rather than the particular subject matter, that is crucial for this brain growth.

Neither can it be ruled out that the differences between the groups are rooted in the individuals selected for the interpreter group. The young people chosen for the intensive training at the interpreter academy were chosen on the basis of their talent for languages. Although brain scans showed no differences between the groups at baseline, we cannot rule out the possibility that such intensive training only benefited them because they possessed this potential for growth.

A final caveat is that the soldiers all underwent basic military training before beginning the course — three months of intense physical exercise. Physical exercise is, of course, usually very beneficial for the brain.

Nevertheless, we must give due weight to the fact that the brain scans of the two groups were comparable at baseline, and the changes discussed occurred specifically during this three-month learning period. Moreover, there is growing evidence that learning a new language is indeed ‘special’, if only because it involves such a complex network of processes and brain regions.

Given that people vary in their ‘talent’ for foreign language learning, and that learning a new language does tend to become harder as we get older, it is worth noting the link between growth of the hippocampus and superior temporal gyrus and language proficiency. The STG is involved in acoustic-phonetic processes, while the hippocampus is presumably vital for the encoding of new words into long-term memory.

Interestingly, previous research with children has suggested that the ability to learn new words is greatly affected by working memory span — specifically, by how much information they can hold in that part of working memory called phonological short-term memory. While this is less important for adults learning another language, it remains important for one particular category of new words: words that have no ready association to known words. Given the languages being studied by these Swedish interpreters, it seems likely that much if not all of their new vocabulary would fall into this category.

I wonder if the link with STG is more significant in this study, because the languages are so different from the students’ native language? I also wonder if, and to what extent, you might be able to improve your phonological short-term memory with this sort of intensive practice.

In this regard, it’s worth noting that a previous study found that language proficiency correlated with growth in the left inferior frontal gyrus in a group of English-speaking exchange students learning German in Switzerland. Is this difference because the training was less intensive? because the students had prior knowledge of German? because German and English are closely related in vocabulary? (I’m picking the last.)

The researchers point out that hippocampal plasticity might also be a critical factor in determining an individual’s facility for learning a new language. Such plasticity does, of course, tend to erode with age — but this can be largely counteracted if you keep your hippocampus limber (as it were).

All these are interesting speculations, but the main point is clear: the findings add to the growing evidence that bilingualism and foreign language learning have particular benefits for the brain, and for protecting against cognitive decline.

Syndicate content