aging

Caffeine may block inflammation linked to cognitive impairment

November, 2012

A mouse study indicates that caffeine can help prevent inflammation occurring in the brain, by blocking an early response to cell damage.

Caffeine has been associated with a lower of developing Alzheimer's disease in some recent studies. A recent human study suggested that the reason lies in its effect on proteins involved in inflammation. A new mouse study provides more support for this idea.

In the study, two groups of mice, one of which had been given caffeine, were exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow. When re-oxygenated, caffeine-treated mice recovered their ability to form a new memory 33% faster than the other mice, and the caffeine was observed to have the same anti-inflammatory effect as blocking interleukin-1 (IL-1) signaling.

Inflammation is a key player in cognitive impairment, and IL-1 has been shown to play a critical role in the inflammation associated with many neurodegenerative diseases.

It was found that the hypoxic episode triggered the release of adenosine, the main component of ATP (your neurons’ fuel). Adenosine is released when a cell is damaged, and this leakage into the environment outside the cell begins a cascade that leads to inflammation (the adenosine activates an enzyme, caspase-1, which triggers production of the cytokine IL-1β).

But caffeine blocks adenosine receptors, stopping the cascade before it starts.

The finding gives support to the idea that caffeine may help prevent cognitive decline and impairment.

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How green tea helps fight cognitive decline & dementia

November, 2012

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.

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Growing the brain with a new language

November, 2012

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.

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Why metabolic syndrome is linked to cognitive decline?

October, 2012

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.

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The study was presented at the Alzheimer's Association International Conference in Vancouver, Canada by Barbara Bendlin.

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New direction for cognitive training in the elderly

October, 2012

A pilot study suggests declines in temporal processing are an important part of age-related cognitive decline, and shows how temporal training can significantly improve some cognitive abilities.

Here’s an exciting little study, implying as it does that one particular aspect of information processing underlies much of the cognitive decline in older adults, and that this can be improved through training. No, it’s not our usual suspect, working memory, it’s something far less obvious: temporal processing.

In the study, 30 older adults (aged 65-75) were randomly assigned to three groups: one that received ‘temporal training’, one that practiced common computer games (such as Solitaire and Mahjong), and a no-activity control. Temporal training was provided by a trademarked program called Fast ForWord Language® (FFW), which was developed to help children who have trouble reading, writing, and learning.

The training, for both training groups, occupied an hour a day, four days a week, for eight weeks.

Cognitive assessment, carried out at the beginning and end of the study, and for the temporal training group again 18 months later, included tests of sequencing abilities (how quickly two sounds could be presented and still be accurately assessed for pitch or direction), attention (vigilance, divided attention, and alertness), and short-term memory (working memory span, pattern recognition, and pattern matching).

Only in the temporal training group did performance on any of the cognitive tests significantly improve after training — on the sequencing tests, divided attention, matching complex patterns, and working memory span. These positive effects still remained after 18 months (vigilance was also higher at the end of training, but this improvement wasn’t maintained).

This is, of course, only a small pilot study. I hope we will see a larger study, and one that compares this form of training against other computer training programs. It would also be good to see some broader cognitive tests — ones that are less connected to the temporal training. But I imagine that, as I’ve discussed before, an effective training program will include more than one type of training. This may well be an important component of such a program.

Reference: 

[3075] Szelag, E., & Skolimowska J.
(2012).  Cognitive function in elderly can be ameliorated by training in temporal information processing.
Restorative Neurology and Neuroscience. 30(5), 419 - 434.

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Why HIV-associated dementia occurs & implications for other disorders

October, 2012

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.

Compounds in green tea and chocolate may help protect brain cells

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)

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More support for value of cognitive activities in fighting cognitive decline in old age

September, 2012

Two recent conference presentations add to the evidence for the benefits of ‘brain training’, and of mental stimulation, for holding back age-related cognitive decline.

My recent reports on brain training for older adults (see, e.g., Review of working memory training programs finds no broader benefit; Cognitive training shown to help healthy older adults; Video game training benefits cognition in some older adults) converge on the idea that cognitive training can indeed be beneficial for older adults’ cognition, but there’s little wider transfer beyond the skills being practiced. That in itself can be valuable, but it does reinforce the idea that the best cognitive training covers a number of different domains or skill-sets. A new study adds little to this evidence, but does perhaps emphasize the importance of persistence and regularity in training.

The study involved 59 older adults (average age 84), of whom 33 used a brain fitness program 5 days a week for 30 minutes a day for at least 8 weeks, while the other group of 26 were put on a waiting list for the program. After two months, both groups were given access to the program, and both were encouraged to use it as much or as little as they wanted. Cognitive testing occurred before the program started, at two months, and at six months.

The first group to use the program used the program on average for 80 sessions, compared to an average 44 sessions for the wait-list group.

The higher use group showed significantly higher cognitive scores (delayed memory test; Boston Naming test) at both two and six months, while the lower (and later) use group showed improvement at the end of the six month period, but not as much as the higher use group.

I’m afraid I don’t have any more details (some details of the training program would be nice) because it was a conference presentation, so I only have access to the press release and the abstract. Because we don’t know exactly what the training entailed, we don’t know the extent to which it practiced the same skills that were tested. But we may at least add it to the evidence that you can improve cognitive skills by regular training, and that the length/amount of training (and perhaps regularity, since the average number of sessions for the wait-list group implies an average engagement of some three times a week, while the high-use group seem to have maintained their five-times-a-week habit) matters.

Another interesting presentation at the conference was an investigation into mental stimulating activities and brain activity in older adults.

In this study, 151 older adults (average age 82) from the Rush Memory and Aging Project answered questions about present and past cognitive activities, before undergoing brain scans. The questions concerned how frequently they engaged in mentally stimulating activities (such as reading books, writing letters, visiting a library, playing games) and the availability of cognitive resources (such as books, dictionaries, encyclopedias) in their home, during their lifetime (specifically, at ages 6, 12, 18, 40, and now).

Higher levels of cognitive activity and cognitive resources were also associated with better cognitive performance. Moreover, after controlling for education and total brain size, it was found that frequent cognitive activity in late life was associated with greater functional connectivity between the posterior cingulate cortex and several other regions (right orbital and middle frontal gyrus, left inferior frontal gyrus, hippocampus, right cerebellum, left inferior parietal cortex). More cognitive resources throughout life was associated with greater functional connectivity between the posterior cingulate cortex and several other regions (left superior occipital gyrus, left precuneus, left cuneus, right anterior cingulate, right middle frontal gyrus, and left inferior frontal gyrus).

Previous research has implicated a decline in connectivity with the posterior cingulate cortex in mild cognitive impairment and Alzheimer’s disease.

Cognitive activity earlier in life was not associated with differences in connectivity.

The findings provide further support for the idea “Use it or lose it!”, and suggests that mental activity protects against cognitive decline by maintaining functional connectivity in important neural networks.

Reference: 

Miller, K.J. et al. 2012. Memory Improves With Extended Use of Computerized Brain Fitness Program Among Older Adults. Presented August 3 at the 2012 convention of the American Psychological Association.

Han, S.D. et al. 2012. Cognitive Activity and Resources Are Associated With PCC Functional Connectivity in Older Adults. Presented August 3 at the 2012 convention of the American Psychological Association.

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Regular cocoa drinking helps those with MCI

September, 2012

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.

 

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Tai Chi improves cognition and brain size in older adults

August, 2012

A comparison of the effects of regular sessions of tai chi, walking, and social discussion, has found tai chi was associated with the biggest gains in brain volume and improved cognition.

The study involved 120 healthy older adults (60-79) from Shanghai, who were randomly assigned to one of four groups: one that participated in three sessions of tai chi every week for 40 weeks; another that instead had ‘social interaction’ sessions (‘lively discussions’); another in which participants engaged in walking around a track; and a non-intervention group included as a control. Brain scans were taken before and after the 40-week intervention, and cognitive testing took place at 20 weeks as well as these times.

Compared to those who received no intervention, both those who participated in tai chi, and those who participated in the social sessions, showed significant increases in brain volume and on some cognitive measures. However, the tai chi group showed improvement on more cognitive tests than the social group (on the Mattis Dementia Rating Scale, the Trailmaking Tests, delayed recognition on the Auditory Verbal Learning Test, and verbal fluency for animals vs verbal fluency and positive trends only on Trails A and the Auditory test).

Surprisingly, there were no such significant effects from the walking intervention, which involved 30 minutes of brisk walking around a 400m circular track, sandwiched by 10 minutes of warm-up and 10 minutes cool-down exercises. This took place in the same park as the tai chi sessions (which similarly included 20 minutes of warm-up exercises, 20 minutes of tai chi, and 10 minutes of cool-down exercises).

This finding is inconsistent with other research, but the answer seems to lie in individual differences — specifically, speed of walking. Faster walkers showed significantly better performance on the Stroop test, and on delayed recall and recognition on the Auditory Verbal Learning Test. It should be noted that, unlike some studies in which participants were encouraged to reach heart-rate targets, participants in this study were simply told to walk at their own speed. This finding, then, would seem to support the view that brisk walking is needed to reap good health and cognitive benefits (which shouldn’t put anyone off — anything is better than nothing! and speed is likely to come with practice, if that’s your aim).

It should also be noted that this population has generally high rates of walking. It is likely, then, that the additional walking in these sessions did not add a great deal to their existing behavior.

There is a caveat to the strongly positive effects of tai chi: this group showed lower cognitive performance at baseline. This was because the group randomly received more individuals with very low scores (8 compared with 5 in the other groups).

The study is, of course, quite a small one, and a larger study is required to confirm these results.

One final note: the relative differences in enjoyment were not explicitly investigated, but the researchers did note that the social group, who initially were given topics to discuss in their hour-long sessions, then decided to select and organize their own discussions, and have continued to do so for two years following the end of the study. It would have been nice if the researchers had re-tested participants at that point.

Reference: 

Mortimer, J.A. et al. 2012. Changes in Brain Volume and Cognition in a Randomized Trial of Exercise and Social Interaction in a Community-Based Sample of Non-Demented Chinese Elders. Journal of Alzheimer's Disease, 30 (4), 757-766.
Full text available at http://health.usf.edu/nocms/publicaffairs/now/pdfs/JAD_Mortimer_30%28201...

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Old honeybees can regain youthful cognition when they return to youthful duties

August, 2012
  • A honey bee study shows how old foraging bees quickly start to decline cognitively, and how this can be reversed in some if they return to more social domestic duties in the hive.

I often talk about the importance of attitudes and beliefs for memory and cognition. A new honey bee study provides support for this in relation to the effects of aging on the brain, and suggests that this principle extends across the animal kingdom.

Previous research has shown that bees that stay in the nest and take care of the young remain mentally competent, but they don’t nurse for ever. When they’re older (after about 2-3 weeks), they become foragers, and foraging bees age very quickly — both physically and mentally. Obviously, you would think, bees ‘retire’ to foraging, and their old age is brief (they begin to show cognitive decline after just two weeks).

But it’s not as simple as that, because in artificial hives where worker bees are all the same age, nurse bees of the same age as foragers don’t show the same cognitive and sensory decline. Moreover, nurse bees have been found to maintain their cognitive abilities for more than 100 days, while foragers die within 18 days and show cognitive declines after 13-15 days (although their ability to assess sweetness remains intact).

The researchers accordingly asked a very interesting question: what happens if the foragers return to babysitting?

To achieve this, they removed all of the younger nurse bees from the nest, leaving only the queen and babies. When the older, foraging bees returned to the nest, activity slowed down for several days, and then they re-organized themselves: some of the old bees returned to foraging; others took on the babysitting and housekeeping duties (cleaning, building the comb, and tending to the queen). After 10 days, around half of these latter bees had significantly improved their ability to learn new things.

This cognitive improvement was also associated with a change in two specific proteins in their brains: one that has been associated with protection against oxidative stress and inflammation associated with Alzheimer disease and Huntington disease in humans (Prx6), and another dubbed a “chaperone” protein because it protects other proteins from being damaged when brain or other tissues are exposed to cell-level stress.

Precisely what it is about returning to the hive that produces this effect is a matter of speculation, but this finding does show that learning impairment in old bees can be reversed by changes in behavior, and this reversal is correlated with specific changes in brain protein.

Having said this, it shouldn’t be overlooked that only some of the worker bees showed this brain plasticity. This is not, apparently, due to differences in genotype, but may depend on the amount of foraging experience.

The findings add weight to the idea that social interventions can help our brains stay younger, and are consistent with growing evidence that, in humans, social engagement helps protect against dementia and age-related cognitive impairment.

The (probably) experience-dependent individual differences shown by the bees is perhaps mirrored in our idea of cognitive reserve, but with a twist. The concept of cognitive reserve emphasizes that accumulating a wealth of cognitive experience (whether through education or occupation or other activities) protects your brain from the damage that might occur with age. But perhaps (and I’m speculating now) we should also consider the other side of this: repeated engagement in routine or undemanding activities may have a deleterious effect, independent of and additional to the absence of more stimulating activities.

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