middle-aged

Diabetes duration and severity associated with brain atrophy

A study involving 614 patients with type 2 diabetes (mean age 62) has found that longer duration of diabetes was associated with more brain volume loss, particularly in the gray matter. Roughly, for every 10 years of diabetes, the brain was similar to that of a non-diabetic person who was two years older.

However, the study did not confirm any association of diabetes characteristics with small vessel ischemic disease.

http://www.eurekalert.org/pub_releases/2014-04/rson-dda042214.php

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Gender affects cardiovascular risk in those with type 2 diabetes

Type 2 diabetes greatly increases a person's risk of developing cardiovascular disease, but a new study shows that cardiovascular risk factors such as elevated blood pressure and cholesterol levels differ significantly between men and women with diabetes.

The study, involving 680 diabetics, found that blood pressure and LDL cholesterol levels were significantly higher in women, and women were significantly less likely to have these factors under control. Some 17% of men had control of these factors, compared to 6% of women.

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Gum disease bacteria may cause heart disease

A mouse study has found that introduction of oral bacteria into the bloodstream increased risk factors for atherosclerotic heart disease, including cholesterol and inflammation, suggesting that the same bacteria that cause gum disease also promotes heart disease. The findings are consistent with recent evidence that patients with gum disease are at higher risk for heart disease.

The findings were presented at the annual meeting of the American Society for Microbiology.

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Early surgical menopause linked to faster cognitive decline

February, 2013

Women who undergo surgical menopause at an earlier age may have an increased risk of cognitive decline.

The issue of the effect of menopause on women’s cognition, and whether hormone therapy helps older women fight cognitive decline and dementia, has been a murky one. Increasing evidence suggests that the timing and type of therapy is critical. A new study makes clear that we also need to distinguish between women who experience early surgical menopause and those who experience natural menopause.

The study involved 1,837 women (aged 53-100), of whom 33% had undergone surgical menopause (removal of both ovaries before natural menopause). For these women, earlier age of the procedure was associated with a faster decline in semantic and episodic memory, as well as overall cognition. The results stayed the same after factors such as age, education and smoking were taken into consideration.

There was also a significant association between age at surgical menopause and the plaques characteristic of Alzheimer's disease. However, there was no significant association with Alzheimer’s itself.

On the positive side, hormone replacement therapy was found to help protect those who had surgical menopause, with duration of therapy linked to a significantly slower decline in overall cognition.

Also positively, age at natural menopause was not found to be associated with rate of cognitive decline.

Reference: 

Bove, R. et al. 2013. Early Surgical Menopause Is Associated with a Spectrum of Cognitive Decline. To be presented at the American Academy of Neurology's 65th Annual Meeting in San Diego, March 21, 2013.

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Why learning gets harder as we get older

February, 2013

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.

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Menopause forgetfulness greatest early in postmenopause

January, 2013

A smallish study suggests that the cognitive effects of menopause are greatest in the first year after menopause.

Being a woman of a certain age, I generally take notice of research into the effects of menopause on cognition. A new study adds weight, perhaps, to the idea that cognitive complaints in perimenopause and menopause are not directly a consequence of hormonal changes, but more particularly, shows that early post menopause may be the most problematic time.

The study followed 117 women from four stages of life: late reproductive, early and late menopausal transition, and early postmenopause. The late reproductive period is defined as when women first begin to notice subtle changes in their menstrual periods, but still have regular menstrual cycles. Women in the transitional stage (which can last for several years) experience fluctuation in menstrual cycles, and hormone levels begin to fluctuate significantly.

Women in the early stage of post menopause (first year after menopause), as a group, were found to perform more poorly on measures of verbal learning, verbal memory, and fine motor skill than women in the late reproductive and late transition stages. They also performed significantly worse than women in the late menopausal transition stage on attention/working memory tasks.

Surprisingly, self-reported symptoms such as sleep difficulties, depression, and anxiety did not predict memory problems. Neither were the problems correlated with hormone levels (although fluctuations could be a factor).

This seemingly contradicts earlier findings from the same researchers, who in a slightly smaller study found that those experiencing poorer working memory and attention were more likely to have poorer sleep, depression, and anxiety. That study, however, only involved women approaching and in menopause. Moreover, these aspects were not included in the abstract of the paper but only in the press release, and because I don’t have access to this particular journal, I cannot say whether there is something in the data that explains this. Because of this, I am not inclined to put too much weight on this point.

But we may perhaps take the findings as support for the view that cognitive problems experienced earlier in the menopause cycle are, when they occur, not a direct result of hormonal changes.

The important result of this study is the finding that the cognitive problems often experienced by women in their 40s and 50s are most acute during the early period of post menopause, and the indication that the causes and manifestations are different at different stages of menopause.

It should be noted, however, that there were only 14 women in the early postmenopause stage. So, we shouldn’t put too much weight on any of this. Nevertheless, it does add to the picture research is building up about the effects of menopause on women’s cognition.

While the researchers said that this effect is probably temporary — which was picked up as the headline in most media — this was not in fact investigated in this study. It would be nice to have some comparison with those, say, two or three and five years post menopause (but quite possibly this will be reported in a later paper).

Reference: 

[3237] Weber, M. T., Rubin L. H., & Maki P. M.
(2013).  Cognition in perimenopause.
Menopause: The Journal of The North American Menopause Society.

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Social isolation decreases myelin

December, 2012

A mouse study demonstrates that prolonged social isolation can lead to a decrease in myelin, an effect implicated in a number of disorders, including age-related cognitive decline.

Problems with myelin — demyelination (seen most dramatically in MS, but also in other forms of neurodegeneration, including normal aging and depression); failure to develop sufficient myelin (in children and adolescents) — are increasingly being implicated in a wide range of disorders. A new animal study adds to that evidence by showing that social isolation brings about both depression and loss of myelin.

In the study, adult mice were isolated for eight weeks (which is of course longer for a mouse than it is to us) to induce a depressive-like state. They were then introduced to a mouse they hadn’t seen before. Although typically very social animals, those who had been socially isolated didn’t show any interest in interacting with the new mouse — a common pattern in human behavior as well.

Analysis of their brains revealed significantly lower levels of gene transcription for oligodendrocyte cells (the components of myelin) in the prefrontal cortex. This appeared to be caused by a lower production of heterochromatin (tightly packed DNA) in the cell nuclei, producing less mature oligodendrocytes.

Interestingly, even short periods of isolation were sufficient to produce changes in chromatin and myelin, although behavior wasn’t affected.

Happily, however, regardless of length of isolation, myelin production went back to normal after a period of social integration.

The findings add to the evidence that environmental factors can have significant effects on brain development and function, and support the idea that socializing is good for the brain.

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Brain training helps cognitive decline in many cancer survivors

November, 2012

A pilot study found that both training in memory strategies and processing speed training had significant benefits for breast cancer survivors with concerns about their memory and cognition.

Cancer survivors who underwent chemotherapy often suffer long-term cognitive problems. Until now, most research has been occupied with establishing that this is in fact the case, and studies investigating how to help have been rare. I recently reported on studies suggesting that help with sleep problems and stress can be beneficial. It has also been suggested that exercise can help. None of these suggestions are special to cancer survivors (although cancer survivors may well be one of several groups that derive particular benefit). Similarly, a new study investigates another familiar approach to improving cognitive decline.

The pilot study involved 82 post-menopausal breast cancer survivors (average age 56) who had received chemotherapy and who were worried about their cognitive abilities. The women were randomly assigned to one of three groups: one group received memory training adapted from the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) trial; another received processing speed training using Posit Science’s Insight program (commercially available); the third was a wait-listed control group.

Training consisted of ten 1-hour small-group (3-5 people) sessions over 6-8 weeks. Memory training involved learning strategies and applying them to word lists, sequences, and texts. Strategies included mnemonic techniques, as well as instruction in principles of meaningfulness, organization, visualization, and association. Strategies were taught and practiced in the first five sessions, and further practiced in the remaining sessions.

In the Insight program, stimulus duration is progressively shortened during a series of progressively more difficult information-processing tasks, such as time-order judgment, discrimination, spatial-match, forward-span, instruction-following, and narrative-memory tasks. Exercises automatically adjust to maintain an 85% correct rate.

Both programs proved beneficial. The memory training group showed significant improvement in immediate and delayed memory, which was maintained at the two-month follow-up. There was of course individual variability: 39% showed significant improvement on immediate memory (compared to 18% of controls) and 42% on delayed memory (compared to 11% of controls). While the group as a whole didn’t show significant improvement in processing speed, some 73% of the group showed reliable improvement at the two-month follow-up.

The Insight group showed significant improvement on both memory and processing speed. Some 68% improved processing speed (compared to 43% of controls). But note that at the 2-month follow-up, the 67% of the Insight group is not that much greater than the 61% of the controls (demonstrating very clearly the benefits of even the small amount of practice received in testing) and is in fact less than the 73% of the memory group.

The Insight group also showed significant improvement in memory. At two-month follow-up, some 30% of the Insight group had improved immediate memory (compared to the 18% of controls), and 33% had improved delayed memory (vs 11%).

Both training programs had a positive effect on perceived cognitive functioning and symptom distress (mood, anxiety, fatigue), and there was no difference between the groups in terms of satisfaction with the training (both groups were very satisfied).

The researchers concluded that, while both training programs were promising, the dual effect of processing speed training (on memory as well as processing speed) argued for its broader benefits.

However, I note that, although the size of the effect of memory training on processing speed was too small to reach statistical significance, the fact that the number of participants showing reliable improvement was greater than that of the Insight group points to an equally broad effect of memory training. If the memory training was supplemented by a small amount of practice on tasks designed to boost processing speed, it would seem to me that this might produce greater cognitive benefits than the processing speed training. Indeed, the Insight program was, I believe, first developed in the context of the ACTIVE program, and I have, of course, talked before about the value of training that includes multiple domains.

Still, the main message of this study should not be overlooked: it demonstrates that many cancer survivors suffering from cognitive decline can improve their cognitive performance through training and practice.

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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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Rapamycin makes young mice learn better and prevents decline in old mice

July, 2012

Further evidence from mice studies that the Easter Island drug improves cognition, in young mice as well as old.

I have reported previously on research suggesting that rapamycin, a bacterial product first isolated from soil on Easter Island and used to help transplant patients prevent organ rejection, might improve learning and memory. Following on from this research, a new mouse study has extended these findings by adding rapamycin to the diet of healthy mice throughout their life span. Excitingly, it found that cognition was improved in young mice, and abolished normal cognitive decline in older mice.

Anxiety and depressive-like behavior was also reduced, and the mice’s behavior demonstrated that rapamycin was acting like an antidepressant. This effect was found across all ages.

Three "feel-good" neurotransmitters — serotonin, dopamine and norepinephrine — all showed significantly higher levels in the midbrain (but not in the hippocampus). As these neurotransmitters are involved in learning and memory as well as mood, it is suggested that this might be a factor in the improved cognition.

Other recent studies have suggested that rapamycin inhibits a pathway in the brain that interferes with memory formation and facilitates aging.

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