MCI

mild cognitive impairment

Link between brain acid and cognition offers hope for an effective ‘smart’ pill

September, 2010

Experiments with mice have found that inhibiting the production of kynurenic acid in the brain has dramatic benefits for cognitive performance.

Commercial use is a long way off, but research with mice offers hope for a ‘smart drug’ that doesn’t have the sort of nasty side-effects that, for example, amphetamines have. The mice, genetically engineered to produce dramatically less (70%) kynurenic acid, had markedly better cognitive abilities. The acid, unusually, is produced not in neurons but in glia, and abnormally high levels are produced in the brains of people with disorders such as schizophrenia, Alzheimer's and Huntington's. More acid is also typically produced as we get older.

The acid is produced in our brains after we’ve eaten food containing the amino acid tryptophan, which helps us produce serotonin (turkey is a food well-known for its high tryptophan levels). But serotonin helps us feel good (low serotonin levels are linked to depression), so the trick is to block the production of kynurenic acid without reducing the levels of serotonin. The next step is therefore to find a chemical that blocks production of the acid in the glia, and can safely be used in humans. Although no human tests have yet been performed, several major pharmaceutical companies are believed to be following up on this research.

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Brain may age faster in people whose hearts pump less blood

September, 2010
  • A large study confirms that your cardiac health affects your brain, and provides evidence that the extent of this problem is greater than we think.

I have often spoken of the mantra: What’s good for your heart is good for your brain. The links between cardiovascular risk factors and cognitive decline gets more confirmation in this latest finding that people whose hearts pumped less blood had smaller brains than those whose hearts pumped more blood. The study involved 1,504 participants of the decades-long Framingham Offspring Cohort who did not have a history of stroke, transient ischemic attack or dementia. Participants were 34 to 84 years old.

Worryingly, it wasn’t simply those with the least amount of blood pumping from the heart who had significantly more brain atrophy (equivalent to almost two years more brain aging) than the people with the highest cardiac index. Those with levels at the bottom end of normal showed similar levels of brain atrophy. Moreover, although only 7% of the participants had heart disease, 30% had a low cardiac index.

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Brain fitness programs may help frail elderly walk faster

September, 2010
  • Walking speed and balance may be improved in seniors through a brain training program. Research has indicated that a common pathology underlies cognitive impairment and gait and balance problems.

On the subject of the benefits of walking for seniors, it’s intriguing to note a recent pilot study that found frail seniors who walked slowly (no faster than one meter per second) benefited from a brain fitness program known as Mindfit. After eight weeks of sessions three times weekly (each session 45-60 minutes), all ten participants walked a little faster, and significantly faster while talking. Walking while talking requires considerably more concentration than normal walking. The success of this short intervention (which needs to be replicated in a larger study) offers the hope that frail elderly who may be unable to participate in physical exercise, could improve their mobility through brain fitness programs. Poor gait speed is also correlated with a higher probability of falls.

The connection between gait speed and cognitive function is an interesting one. Previous research has indicated that slow gait should alert doctors to check for cognitive impairment. One study found severe white matter lesions were more likely in those with gait and balance problems. Most recently, a longitudinal study involving over 900 older adults has found poorer global cognitive function, verbal memory, and executive function, were all predictive of greater decline in gait speed.

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Depression increases risk of dementia

August, 2010
  • New data from a large long-running study provides more conclusive evidence that depression is indeed a risk factor for dementia.

Data from the long-running Framingham Heart Study has revealed that depression significantly increased the risk of developing dementia. Of the 125 people (13%) who were classified as having depression at the start of the study, 21.6% had developed dementia by the end of the study (17 years later). This compares to around 16.6% of those who weren’t depressed. When age, gender, education, homocysteine, and APOE gene status were taken into account, depressed participants had a more than 50% increased risk of developing dementia. Moreover, for each 10-point increase on the self-report scale used to measure depression (CES-D), there was a significant increase in the dementia risk. These findings, from one of the largest and longest population-based studies, should clarify the inconsistent results from earlier research.

There are several possible ways depression might increase the risk of dementia — for example, through the brain inflammation or the increased level of certain proteins that occurs during depression; or through the effects on lifestyle (reduced exercise, social engagement, poor diet).

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Common medications increase risk of mild cognitive impairment

August, 2010

A large study of older African-Americans has found taking common medications with anticholinergic effects was correlated with an increased risk of developing mild cognitive impairment.

Anticholinergics are widely used for a variety of common medical conditions including insomnia, allergies, or incontinence, and many are sold over the counter. Now a large six-year study of older African-Americans has found that taking one anticholinergic significantly increased an individual's risk of developing mild cognitive impairment and taking two of these drugs doubled this risk. The risk was greater for those who didn’t have the ‘Alzheimer’s gene’, APOE-e4.

This class of drugs includes Benadryl®, Dramamine®, Excedrin PM®, Nytol®, Sominex®, Tylenol PM®, Unisom®, Paxil®, Detrol®, Demerol® and Elavil® (for a more complete list of medications with anticholinergic effects, go to http://www.indydiscoverynetwork.org/AnticholienrgicCognitiveBurdenScale....).

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Low vitamin D levels associated with cognitive decline

August, 2010

Another study shows that older adults with low levels of vitamin D have higher levels of cognitive decline, particularly in executive function (but not attention).

Another study has come out showing that older adults with low levels of vitamin D are more likely to have cognitive problems. The six-year study followed 858 adults who were age 65 or older at the beginning of the study. Those who were severely deficient in vitamin D were 60% more likely to have substantial cognitive decline, and 31% more likely to have specific declines in executive function, although there was no association with attention. Vitamin D deficiency is common in older adults in the United States and Europe (levels estimated from 40% to 100%!), and has been implicated in a wide variety of physical disease.

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Specific hippocampal atrophy early sign of MCI & Alzheimer's

January, 2010
  • People with MCI who later developed Alzheimer's disease showed 10-30% greater brain atrophy in two specific regions.

A three-year study involving 169 people with mild cognitive impairment has found that those who later developed Alzheimer's disease showed 10-30% greater atrophy in two specific locations within the hippocampus, the cornu ammonis (CA1) and the subiculum. A second study comparing the brains of 10 cognitively normal elderly people and seven who were diagnosed with MCI between two and three years after their initial brain scan and with Alzheimer's some seven years after the initial scan, has confirmed the same pattern of hippocampal atrophy, from the CA1 to the subiculum, and then other regions of the hippocampus.

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Apostolova, L.G. et al. In press. Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal. Neurobiology of Aging, Available online 24 September 2008.

[392] Apostolova, L. G., Thompson P. M., Green A. E., Hwang K. S., Zoumalan C., Jack, Jr C. R., et al.
(2010).  3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.
Human Brain Mapping. 9999(9999), NA - NA.

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Subjective memory loss may increase risk for MCI & dementia

January, 2010

Healthy older adults reporting subjective cognitive impairment are dramatically more likely to progress to MCI or dementia, and decline significantly faster.

Subjective cognitive impairment (SCI), marked by situations such as when a person recognizes they can't remember a name like they used to or where they recently placed important objects the way they used to, is experienced by between one-quarter and one-half of the population over the age of 65. A seven-year study involving 213 adults (mean age 67) has found that healthy older adults reporting SCI are dramatically more likely to progress to MCI or dementia than those free of SCI (54% vs 15%). Moreover, those who had SCI declined significantly faster.

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Reisberg, B. et al. 2010. Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimer's & Dementia, 6 (1), 11-24.

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Exercise helps prevent, improve MCI

January, 2010

Two large studies have found moderate exercise was associated with a lower risk of developing mild cognitive impairment. A small study suggests women may benefit more than men.

A German study involving nearly 4000 older adults (55+) has found that physical activity significantly reduced the risk of developing mild cognitive impairment over a two-year period. Nearly 14% of those with no physical activity at the start of the study developed cognitive impairment, compared to 6.7% of those with moderate activity, and 5.1% of those with high activity. Moderate activity was defined as less than 3 times a week.

In another report, a study involving 1,324 individuals without dementia found those who reported performing moderate exercise during midlife or late life were significantly less likely to have MCI. Midlife moderate exercise was associated with 39% reduction in the odds of developing MCI, and moderate exercise in late life was associated with a 32% reduction. Light exercise (such as bowling, slow dancing or golfing with a cart) or vigorous exercise (including jogging, skiing and racquetball) were not significantly associated with reduced risk for MCI.

And in a clinical trial involving 33 older adults (55-85) with MCI has found that women who exercised at high intensity levels with an aerobics trainer for 45 to 60 minutes per day, four days per week, significantly improved performance on multiple tests of executive function, compared to those who engaged in low-intensity stretching exercises. The results for men were less significant: high-intensity aerobics was associated only with improved performance on one cognitive task, Trail-making test B, a test of visual attention and task-switching.

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Blueberry juice & purple grape juice improve memory in older adults

January, 2010

Two small studies provide the first human evidence that blueberries and Concord grape juice can improve verbal memory in those with mild cognitive impairment.

A number of rodent studies have shown that blueberries can improve aging memory; now for the first time, a human study provides evidence. In the small study, nine older adults (mean age 76) with mild cognitive impairment (MCI) drank the equivalent of 2-2 l/2 cups of a commercially available blueberry juice every day. After three months they showed significantly improved paired associate learning and word list recall. The findings will of course have to be confirmed by larger trials, but they are consistent with other research.

A companion study involving 12 older adults (75-80) with MCI found that those who drank a pure variety of Concord grape juice for 12 weeks also saw their performance progressively improve on tests in which they had to learn lists and remember items placed in a certain order.

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