MCI

mild cognitive impairment

Walk for your brain’s sake

November, 2010

Walking helps older adults fight brain shrinkage, which is in turn associated with a reduced risk of cognitive impairment and dementia.

A long-running study involving 299 older adults (average age 78) has found that those who walked at least 72 blocks during a week of recorded activity (around six to nine miles) had greater gray matter volume nine years later. Gray matter does shrink as we get older, so this is not about growth so much as counteracting decline. Walking more than 72 blocks didn’t appear to confer any additional benefit (in terms of gray matter volume). Moreover, when assessed four years after that, those who had shown this increased brain size were only half as likely to have developed dementia (40% of the participants had developed dementia by this point).

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70-year-olds smarter than they used to be

November, 2010

Findings from a large Swedish study are consistent with the hypothesis that more education and better healthcare have produced less cognitive impairment in present-day older adults.

Beginning in 1971, healthy older adults in Gothenburg, Sweden, have been participating in a longitudinal study of their cognitive health. The first H70 study started in 1971 with 381 residents of Gothenburg who were 70 years old; a new one began in 2000 with 551 residents and is still ongoing. For the first cohort (born in 1901-02), low scores on non-memory tests turned out to be a good predictor of dementia; however, these tests were not predictive for the generation born in 1930. Those from the later cohort also performed better in the intelligence tests at age 70 than their predecessors had.

It’s suggested that the higher intelligence is down to the later cohort’s better pre and postnatal care, better nutrition, higher quality education, and better treatment of high blood pressure and cholesterol. And possibly the cognitive demands of modern life.

Nevertheless, the researchers reported that the incidence of dementia at age 75 was little different (5% in the first cohort and 4.4% in the later). However, since a substantially greater proportion of the first cohort were dead by that age (15.7% compared to 4.4% of the 2nd cohort), it seems quite probable that there really was a higher incidence of dementia in the earlier cohort.

The fact that low scores on non-memory cognitive tests were predictive in the first cohort of both dementia and death by age 75 supports this argument.

The fact that low scores on non-memory cognitive tests were not predictive of dementia or death in the later cohort is in keeping with the evidence that higher levels of education help delay dementia. We will need to wait for later findings from this study to see whether that is what is happening.

The findings are not inconsistent with those from a very large U.S. national study that found older adults (70+) are now less likely to be cognitively impaired (see below). It was suggested then also that better healthcare and more education were factors behind this decline in the rate of cognitive impairment.

Previous study:

A new nationally representative study involving 11,000 people shows a downward trend in the rate of cognitive impairment among people aged 70 and older, from 12.2% to 8.7% between 1993 and 2002. It’s speculated that factors behind this decline may be that today’s older people are much likelier to have had more formal education, higher economic status, and better care for risk factors such as high blood pressure, high cholesterol and smoking that can jeopardize their brains. In fact the data suggest that about 40% of the decrease in cognitive impairment over the decade was likely due to the increase in education levels and personal wealth between the two groups of seniors studied at the two time points. The trend is consistent with a dramatic decline in chronic disability among older Americans over the past two decades.

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Insulin sensitivity may explain link between obesity, memory problems

November, 2010

A new study suggests that the link between midlife obesity and cognitive impairment and dementia in old age may be explained by poorer insulin sensitivity.

Previous research has indicated that obesity in middle-age is linked to higher risk of cognitive decline and dementia in old age. Now a study of 32 middle-aged adults (40-60) has revealed that although obese, overweight and normal-weight participants all performed equally well on a difficult cognitive task (a working memory task called the 2-Back task), obese individuals displayed significantly lower activation in the right inferior parietal cortex. They also had lower insulin sensitivity than their normal weight and overweight peers (poor insulin sensitivity may ultimately lead to diabetes). Analysis pointed to the impaired insulin sensitivity mediating the relationship between task-related activation in that region and BMI.

This suggests that it is insulin sensitivity that is responsible for the higher risk of cognitive impairment later in life. The good news is that insulin sensitivity is able to be modified through exercise and diet.

A follow-up study to determine if a 12-week exercise intervention can reverse the differences is planned.

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Compound in celery, peppers reduces age-related memory deficits

November, 2010

One precursor of age-related cognitive impairment and dementia is inflammation. Research suggests why that might be, and explains why the plant nutrient luteolin can help fight memory impairment.

Inflammation in the brain appears to be a key contributor to age-related memory problems, and it may be that this has to do with the dysregulation of microglia that, previous research has shown, occurs with age. As these specialized support cells in the brain do normally when there’s an infection, with age microglia start to produce excessive cytokines, some of which result in the typical behaviors that accompany illness (sleepiness, appetite loss, cognitive deficits and depression).

Now new cell and mouse studies suggests that the flavenoid luteolin, known to have anti-inflammatory properties, apparently has these benefits because it acts directly on the microglial cells to reduce their production of inflammatory cytokines. It was found that although microglia exposed to a bacterial toxin produced inflammatory cytokines that killed neurons, if the microglia were first exposed to luteolin, the neurons lived. Exposing the neuron to luteolin had no effect.

Old mice fed a luteolin-supplemented diet for four weeks did better on a working memory test than old mice on an ordinary diet, and restored levels of inflammatory cytokines in their brains to that of younger mice.

Luteolin is found in many plants, including carrots, peppers, celery, olive oil, peppermint, rosemary and chamomile.

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Mental activity may slow cognitive decline initially, but speed up dementia later

October, 2010

Another study has come out suggesting that the advantage of mental stimulation is to delay cognitive decline, but at the cost of faster decline later (it’s still a good bargain).

A long-running study involving 1,157 healthy older adults (65+) who were scored on a 5-point scale according to how often they participated in mental activities such as listening to the radio, watching television, reading, playing games and going to a museum, has found that this score is correlated to the rate of cognitive decline in later years.

Some 5 ½ years after this initial evaluation, 395 (34%) were found to have mild cognitive impairment and 148 (13%) to have Alzheimer’s. Participants were then tested at 3-yearly intervals for the next 6 years. The rate of cognitive decline in those without cognitive impairment was reduced by 52% for each point on the cognitive activity scale, but for those with Alzheimer's disease, the average rate of decline per year increased by 42% for each point on the cognitive activity scale. Rate of decline was unrelated to earlier cognitive activity in those with MCI (presumably they were at the balance point).

This is not terribly surprising when you think of it, if you assume that the benefit of mental stimulation is to improve your brain function so that it can better cope with the damage happening to it. But eventually it reaches the point where it can no longer compensate for that damage because it is so overwhelming.

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Low levels of omega-3 fatty acid may contribute to Alzheimer’s

October, 2010

A finding that the livers of Alzheimer’s patients have an impaired ability to make the omega-3 fatty acid DHA may suggest a new approach.

Low levels of DHA, an omega-3 fatty acid, have been found in the brains of those with Alzheimer's disease, but the reason has not been known. A new study has found that lower levels of DHA in the liver (where most brain DHA is manufactured) were correlated with greater cognitive problems in the Alzheimer’s patients. Moreover, comparison of postmortem livers from Alzheimer’s patients and controls found reduced expression of a protein that converts a precursor acid into DHA, meaning the liver was less able to make DHA from food.

The findings may explain why clinical trials in which Alzheimer's patients are given omega-3 fatty acids have had mixed results. They also suggest that it might be possible to identify at-risk persons using specific blood tests, and perhaps delay the development of Alzheimer’s with a chemically enhanced form of DHA.

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Cognitive decline is not simply a function of getting old

October, 2010
  • New research suggests that even “normal” cognitive decline with age reflects the type of brain damage that is (in greater amount) characteristic of dementia.

Findings from the long-running Religious Orders Study, from 354 Catholic nuns and priests who were given annual cognitive tests for up to 13 years before having their brains examined post-mortem, has revealed that even the very early cognitive impairments we regard as normal in aging are associated with dementia pathology. Although pathology in the form of neurofibrillary tangles, Lewy bodies, and cerebral infarctions were all associated with rapid decline, they were also associated with “normal” mild impairment. In the absence of any of these lesions, there was almost no cognitive decline.

Previous research has shown that white matter lesions are very common in older adults, and mild cognitive impairment is more likely in those with quickly growing white matter lesions; importantly, the crucial factor appears to be the rate of growth, not the amount of lesions. This new study extends the finding, suggesting that any age-related cognitive impairment reflects the sort of brain pathology that ultimately leads to dementia (if given enough time). It suggests that we should be more proactive in fighting such damage, instead of simply regarding it as normal.

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Factors linked to cognitive deficits in type 2 diabetes

October, 2010

Cognitive deficits and even dementia are more common in older diabetics. A new study points to three health issues that, if present, increase the risk that older diabetics will develop cognitive problems.

Type 2 diabetes is known to increase the risk of cognitive impairment in old age. Now analysis of data from 41 older diabetics (aged 55-81) and 458 matched controls in the Victoria Longitudinal Study has revealed that several other factors make it more likely that an older diabetic will develop cognitive impairment. These factors are: having higher (though still normal) blood pressure, having gait and balance problems, and/or reporting yourself to be in bad health regardless of actual problems.

Diabetes and hypertension often go together, and both are separately associated with greater cognitive impairment and dementia risk, so it is not surprising that higher blood pressure is one of the significant factors that increases risk. The other factors are less expected, although gait and balance problems have been linked to cognitive impairment in a recent study, and they may be connected to diabetes through diabetes’ effect on nerves. Negativity about one’s health may reflect emotional factors such as anxiety, stress, or depression, although depression and well-being measures were not themselves found to be mediating effects for cognitive impairment in diabetics (Do note that this study is not investigating which factors, in general, are associated with age-related cognitive impairment; it is trying to establish which factors are specifically sensitive to cognitive impairment in older diabetics).

In the U.S., type 2 diabetes occurs in over 23% of those over 60; in Canada (where this study took place) the rate is 19%. It should be noted that the participants in this study are not representative of the general population, in that they were fairly well-educated older Canadians, most of whom have benefited from a national health care system. Moreover, the study did not have longitudinal data on these various factors, meaning that we don’t know the order of events (which health problems come first? How long between the development of the different problems?). Nevertheless, the findings provide useful markers to alert diabetics and health providers.

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Memory problems more common in older men?

October, 2010

A large community study of older adults has found mild cognitive impairment was more prevalent in men.

A study involving 2,050 people aged 70 to 89 has found that mild cognitive impairment was 1.5 times more common in men than women. Among the 1,969 who did not have dementia, over 16% (329) had MCI — around 11% amnestic MCI (MCI-A) and 5% non-amnestic (MCI-MCD). A total of 19% of men had MCI, compared to 14% of women. MCI was also more common among the never-married, those with the APOEe4 (Alzheimer’s risk) gene, and those with less education.

This is the first study conducted among community-dwelling persons to find a higher prevalence of MCI in men. However, I note that some years ago I reported on a Dutch study involving some 600 85-year-olds, that found that significantly more women than men had a good memory (41% vs 29%; good mental speed on word and number recognition tests was also found in more women than men: 33% vs 28%). This was considered particularly surprising, given that significantly more of the women had limited formal education compared to the men.

The researchers suggested biological factors such as the relative absence of cardiovascular disease in the women might account for the difference. I would suggest another factor might be social, given that social stimulation has been shown to help prevent cognitive decline, and women are more likely than men to keep up social links in old age.

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Vitamin B supplements could delay onset of Alzheimer's

September, 2010
  • Vitamin B supplements markedly reduced brain atrophy in older adults with MCI, offering hope that they may be effective in delaying the development of Alzheimer’s.

A two-year study involving 271 older adults (70+) with mild cognitive impairment has found that the rate of brain atrophy in those taking folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), was significantly slower than in those taking a placebo, with those taking the supplements experiencing on average 30% less brain atrophy. Higher rates of atrophy were associated with lower cognitive performance. Moreover those who with the highest levels of homocysteine at the beginning of the trial benefited the most, with 50% less brain shrinkage. High levels of homocysteine are a risk factor for Alzheimer’s, and folate, B12 and B6 help regulate it.

The finding that atrophy can be slowed in those with MCI offers hope that the treatment could delay the development of Alzheimer’s, since MCI is a major risk factor for Alzheimer’s, and faster brain atrophy is typical of those who go on to develop Alzheimer’s.

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