brain atrophy

Obesity linked to better cognition in post-menopausal women

November, 2011
  • A new study suggests fat might help protect women from age-related cognitive decline.

Obesity has been linked to cognitive decline, but a new study involving 300 post-menopausal women has found that higher BMI was associated with higher cognitive scores.

Of the 300 women (average age 60), 158 were classified as obese (waist circumference of at least 88cm, or BMI of over 30). Cognitive performance was assessed in three tests: The Mini-Mental Statement Examination (MMSE), a clock-drawing test, and the Boston Abbreviated Test.

Both BMI and waist circumference were positively correlated with higher scores on both the MMSE and a composite cognitive score from all three tests. It’s suggested that the estrogen produced in a woman’s fat cells help protect cognitive function.

Interestingly, a previous report from the same researchers challenged the link found between metabolic syndrome and poorer cognitive function. This study, using data from a large Argentinean Cardiovascular Prevention Program, found no association between metabolic syndrome and cognitive decline — but the prevalence of metabolic syndrome and cognitive decline was higher in males than females. However, high inflammatory levels were associated with impairment of executive functions, and higher systolic blood pressure was associated with cognitive decline.

It seems clear that any connection between BMI and cognitive decline is a complex one. For example, two years ago I reported that, among older adults, higher BMI was associated with more brain atrophy (replicated below; for more recent articles relating obesity to cognitive impairment, click on the obesity link at the end of this report). Hypertension, inflammation, and diabetes have all been associated with greater risk of impairment and dementia. It seems likely that the connection between BMI and impairment is mediated through these and other factors. If your fat stores are not associated with such health risk factors, then the fat in itself is not likely to be harmful to your brain function — and may (if you’re a women) even help.

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Overweight and obese elderly have smaller brains

Analysis of brain scans from 94 people in their 70s who were still "cognitively normal" five years after the scan has revealed that people with higher body mass indexes had smaller brains on average, with the frontal and temporal lobes particularly affected (specifically, in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus, in obese people, and in the basal ganglia and corona radiate of the overweight). The brains of the 51 overweight people were, on average, 6% smaller than those of the normal-weight participants, and those of the 14 obese people were 8% smaller. To put it in more comprehensible, and dramatic terms: "The brains of overweight people looked eight years older than the brains of those who were lean, and 16 years older in obese people." However, overall brain volume did not differ between overweight and obese persons. As yet unpublished research by the same researchers indicates that exercise protects these same brain regions: "The most strenuous kind of exercise can save about the same amount of brain tissue that is lost in the obese."

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Zilberman, J.M., Del Sueldo, M., Cerezo, G., Castellino, S., Theiler, E. & Vicario, A. 2011. Association Between Menopause, Obesity, and Cognitive Impairment. Presented at the Physiology of Cardiovascular Disease: Gender Disparities conference, October 12, at the University of Mississippi in Jackson.

Vicario, A., Del Sueldo, M., Zilberman, J. & Cerezo, G.H. 2011. The association between metabolic syndrome, inflammation and cognitive decline. Presented at the European Society of Hypertension (ESH) 2011: 21st European Meeting on Hypertension, June 17 - 20, Milan, Italy.

[733] Thompson, P. M., Raji C. A., Ho A. J., Parikshak N. N., Becker J. T., Lopez O. L., et al.
(2010).  Brain structure and obesity.
Human Brain Mapping. 31(3), 353 - 364.

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More evidence of the benefits of B vitamins in fighting cognitive decline

September, 2011
  • High daily doses of B-vitamins significantly slowed cognitive decline and brain atrophy in those with MCI, especially if they had high levels of homocysteine.

In a small study, 266 older adults with mild cognitive impairment (aged 70+) received a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B12 and 20 mg vitamin B6 or a placebo for two years. Those treated with B vitamins had significantly lower levels of homocysteine at the end of the trial (high homocysteine is a known risk factor for age-related cognitive decline and dementia). Moreover, this was associated with a significantly slower rate of brain shrinkage.

However, while there were significant effects on homocysteine level, brain atrophy, and executive function, it wasn’t until results were separated on the basis of baseline homocysteine levels that we get really dramatic results.

It was the group with high homocysteine levels at the start of the study who really benefited from the high doses of B vitamins. For them, brain atrophy was cut by half, and there were clear benefits in episodic memory, semantic memory, and global cognitive function, not just executive function. Among those with high baseline homocysteine who received the placebo, significant cognitive decline occurred.

The level of B vitamins in the supplements was considerably greater than the recommended standard. However, caution must be taken in dosing yourself with supplements, because folic acid can have negative effects. Better to try and get your diet right first.

A longer and larger follow-up study is now planned, and hopefully that will tell us if such treatment can keep MCI developing into Alzheimer’s.

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Memory loss in old age the price we pay for a large brain & a long life?

September, 2011
  • Chimpanzee brains don’t shrink with age as humans’ do. It may be that cognitive impairment and even dementia are our lot because we work our brains too hard for too long.

Comparison of 99 chimpanzee brains ranging from 10-51 years of age with 87 human brains ranging from 22-88 years of age has revealed that, unlike the humans, chimpanzee brains showed no sign of shrinkage with age. But the answer may be simple: we live much longer. In the wild, chimps rarely live past 45, and although human brains start shrinking as early as 25 (as soon as they reach maturity, basically!), it doesn’t become significant until around 50.

The answer suggests one reason why humans are uniquely vulnerable to Alzheimer’s disease — it’s all down to our combination of large brain and long life. There are other animals that experience some cognitive impairment and brain atrophy as they age, but nothing as extreme as that found in humans (a 10-15% decline in volume over the life-span). (Elephants and whales have the same two attributes as humans — large brains and long lives — but we lack information on how their brains change with age.)

The problem may lie in the fact that our brains use so much more energy than chimps’ (being more than three times larger than theirs) and thus produce a great deal more damaging oxidation. Over a longer life-span, this accumulates until it significantly damages the brain.

If that’s true, it reinforces the value of a diet high in antioxidants.

Reference: 

[2500] Sherwood, C. C., Gordon A. D., Allen J. S., Phillips K. A., Erwin J. M., Hof P. R., et al.
(2011).  Aging of the cerebral cortex differs between humans and chimpanzees.
Proceedings of the National Academy of Sciences. 108(32), 13029 - 13034.

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Alzheimer's disease symptoms more subtle in people over 80

September, 2011
  • A new study shows that, among the very old, it’s harder to distinguish between normal brain atrophy and cognitive impairment and that indicative of Alzheimer’s.

A study involving 105 people with Alzheimer's disease and 125 healthy older adults has compared cognitive function and brain shrinkage in those aged 60-75 and those aged 80+.

It was found that the association between brain atrophy and cognitive impairment typically found in those with Alzheimer’s disease was less evident in the older group. This is partly because of the level of brain atrophy in healthy controls in that age group — there was less difference between the healthy controls and those with Alzheimer’s. Additionally, when compared to their healthy counterparts, executive function, immediate memory and attention/processing speed were less abnormal in the older group than they were in the younger group.

The finding suggests that mild Alzheimer’s in the very old may go undetected, and emphasize the importance of taking age into account when interpreting test performance and brain measures.

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Religious factors may influence brain shrinkage in old age

July, 2011
  • An intriguing new study suggests life-changing religious experiences may result in greater brain shrinkage in old age.

The brain tends to shrink with age, with different regions being more affected than others. Atrophy of the hippocampus, so vital for memory and learning, is associated with increased risk of developing Alzheimer’s, and has also been linked to depression.

In a study involving 268 older adults (58+), the hippocampus of those reporting a life-changing religious experience was found to be shrinking significantly more compared to those not reporting such an experience. Significantly greater hippocampal atrophy was also found among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again.

The participants are not a general sample — they were originally recruited for the NeuroCognitive Outcomes of Depression in the Elderly. However, some of the participants were from the control group, who had no history of depression. Brain scans were taken at the beginning of the study, and then every two years. The length of time between the baseline scan and the final scan ranged from 2 to 8 years (average was 4).

Questions about religious experiences were asked in an annual survey, so could change over time. Two-thirds of the group was female, and 87% were white. The average age was 68. At baseline, 42% of the group was non-born-again Protestant, 36% born-again Protestant; 8% Catholic; 6% other religion. Only 7% reported themselves as having no religion. By the end of the study, 44% (119 participants) reported themselves born-again, and 13% (36) reported having had life-changing religious experiences.

These associations persisted after depression status, acute stress, and social support were taken into account. Nor did other religious factors (such as prayer, meditation, or Bible study) account for the changes.

It is still possible that long-term stress might play a part in this association — the study measured acute rather than cumulative stress. The researchers suggest that life-changing religious experiences can be stressful, if they don’t fit in with your existing beliefs or those of your family and friends, or if they lead to new social systems that add to your stress.

Of course, the present results can be interpreted in several ways — is it the life-changing religious experience itself that is the crucial factor? Or the factors leading up to that experience? Or the consequences of that experience? Still, it’s certainly an intriguing finding, and it will be interesting to see more research expanding and confirming (or not!) this result.

More generally, the findings may help clarify the conflicting research about the effects of religion on well-being, by pointing to the fact that religion can’t be considered a single factor, but one subject to different variables, some of which may be positive and others not.

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Alzheimer's diagnostic guidelines updated

June, 2011
  • Updated clinical guidelines now cover three distinct stages of Alzheimer's disease.

For the first time in 27 years, clinical diagnostic criteria for Alzheimer's disease dementia have been revised, and research guidelines updated. They mark a major change in how experts think about and study Alzheimer's disease.

The updated guidelines now cover three distinct stages of Alzheimer's disease:

  • Preclinical – is currently relevant only for research. It describes the use of biomarkers that may precede the development of Alzheimer’s.
  • Mild Cognitive Impairment– Current biomarkers include elevated levels of tau or decreased levels of beta-amyloid in the cerebrospinal fluid, reduced glucose uptake in the brain, and atrophy of certain brain regions. Primarily for researchers, these may be used in specialized clinical settings.
  • Alzheimer's Dementia – Criteria outline ways clinicians should approach evaluating causes and progression of cognitive decline, and expand the concept of Alzheimer's dementia beyond memory loss to other aspects of cognition, such as word-finding, vision/spatial issues, and impaired reasoning or judgment.

The criteria are available at http://www.alzheimersanddementia.org/content/ncg

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Long-term users of ecstasy risk structural brain damage

June, 2011
  • A small study suggests that regular ecstasy use produces brain atrophy, especially in the hippocampus.

Imaging the brains of 10 young men who were long term users of ecstasy and seven of their healthy peers with no history of ecstasy use has revealed a significantly smaller hippocampus in those who used ecstasy. The overall proportion of gray matter was also lower, suggesting the effects of ecstasy may not be restricted to the hippocampus.

Both groups had used similar amounts of recreational drugs other than ecstasy, and drank alcohol regularly. The ecstasy group had not taken ecstasy for more than two months before the start of the study on average.

Reference: 

[2218] den Hollander, B., Schouw M., Groot P., Huisman H., Caan M., Barkhof F., et al.
(2011).  Preliminary evidence of hippocampal damage in chronic users of ecstasy.
Journal of Neurology, Neurosurgery & Psychiatry.

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More evidence that Alzheimer's disease may be inherited from your mother

March, 2011
  • A new study adds to growing evidence that having a mother with Alzheimer's disease is a greater risk factor than if your father suffered the disease.

A two-year study involving 53 older adults (60+) has found that those with a mother who had Alzheimer's disease had significantly more brain atrophy than those with a father or no parent with Alzheimer's disease. More specifically, they had twice as much gray matter shrinkage, and about one and a half times more whole brain shrinkage per year.

This atrophy was particularly concentrated in the precuneus and parahippocampal gyrus. Those with the APOE4 gene also had more atrophy in the frontal cortex than those who didn’t carry the ‘Alzheimer’s gene’.

This adds to evidence indicating that maternal history is a far greater risk factor for Alzheimer’s than paternal history. Eleven participants reported having a mother with Alzheimer's disease, 10 had a father with Alzheimer's disease and 32 had no family history of the disease. It has been estimated that people who have first-degree relatives with Alzheimer's disease are four to 10 times more likely to develop the disease.

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The importance of the cerebellum for intelligence and age-related cognitive decline

March, 2011
  • A new study of older adults indicates atrophy of the cerebellum is an important factor in cognitive decline for men, but not women.

Shrinking of the frontal lobe has been associated with age-related cognitive decline for some time. But other brain regions support the work of the frontal lobe. One in particular is the cerebellum. A study involving 228 participants in the Aberdeen Longitudinal Study of Cognitive Ageing (mean age 68.7) has revealed that there is a significant relationship between grey matter volume in the cerebellum and general intelligence in men, but not women.

Additionally, a number of other brain regions showed an association between gray matter and intelligence, in particular Brodmann Area 47, the anterior cingulate, and the superior temporal gyrus. Atrophy in the anterior cingulate has been implicated as an early marker of Alzheimer’s, as has the superior temporal gyrus.

The gender difference was not completely unexpected — previous research has indicated that the cerebellum shrinks proportionally more with age in men than women. More surprising was the fact that there was no significant association between white memory volume and general intelligence. This contrasts with the finding of a study involving older adults aged 79-80. It is speculated that this association may not develop until greater brain atrophy has occurred.

It is also interesting that the study found no significant relationship between frontal lobe volume and general intelligence — although the effect of cerebellar volume is assumed to occur via its role in supporting the frontal lobe.

The cerebellum is thought to play a vital role in three relevant areas: speed of information processing; variability of information processing; development of automaticity through practice.

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Exercise improves executive function and math in sedentary children

February, 2011
  • A three-month trial comparing the effects of exercise programs on cognitive function in sedentary, overweight children, has found dose-related benefits of regular aerobic exercise.

A study involving 171 sedentary, overweight 7- to 11-year-old children has found that those who participated in an exercise program improved both executive function and math achievement. The children were randomly selected either to a group that got 20 minutes of aerobic exercise in an after-school program, one that got 40 minutes of exercise in a similar program, or a group that had no exercise program. Those who got the greater amount of exercise improved more. Brain scans also revealed increased activity in the prefrontal cortex and reduced activity in the posterior parietal cortex, for those in the exercise group.

The program lasted around 13 weeks. The researchers are now investigating the effects of continuing the program for a full year. Gender, race, socioeconomic factors or parental education did not change the impact of the exercise program.

The effects are consistent with other studies involving older adults. It should be emphasized that these were sedentary, overweight children. These findings are telling us what the lack of exercise is doing to young minds. I note the report just previous, about counteracting what we have regarded as “normal” brain atrophy in older adults by the simple action of walking for 40 minutes three times a week. Children and older adults might be regarded as our canaries in the coal mine, more vulnerable to many factors that can affect the brain. We should take heed.

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